Clinical Focus

  • Sports Medicine
  • Orthopaedic Surgery

Academic Appointments

Administrative Appointments

  • Team Physician, Stanford Athletic Department (2005 - Present)
  • Head, Team Physician, Stanford Football Program (2007 - Present)

Honors & Awards

  • Junior Alpha Omega Alpha Honor Society, University of Arizona College of Medicine (1996)
  • McGraw-Hill Award-Top Medical Student in the basic sciences, University of Arizona College of Medicine (1996)
  • University of Arizona Foundation Top Medical Student at Graduation, University of Arizona College of Medicine (1998)
  • Bernard Revsin Scholarship Award for Academic Excellence, University of Arizona College of Medicine (1998)
  • Zimmer Research Award, American Orthopaedic Association (2001)
  • Best and Brightest: Current Research in Surgery. Award-Winning Studies by California Surgeons, American College of Surgeons (2001)
  • Orthopaedic Hospital Research Award, California Orthopaedic Association (2002)
  • Basic Science Manuscript Award Smith and Nephew National Research Awards Conference, Smith and Nephew (2002)
  • Zimmer Research Award, American Orthopaedic Association (2002)
  • Aventis Orthopaedic Research Scholarship, UCLA Department of Orthopaedics (2002)
  • Investigation of treatments for osteochondral defects in children-Educational Grant, Shriners Hospital System for Children (2003)
  • InScope Orthopeadic Research Grant, Innovative Scientific Centers of Orthopaedic Excellence Orthopaedic (2005)
  • Basic Science Research Award, Smith and Nephew (2006)
  • Bone and Joint Decade Young Investigator Award, Bone and Joint Decade (2006)
  • North American representative for Scientific Exchange with Europe, AOSSM/ESSKA (2008)
  • Listed in Top US Orthopeadic Surgeons in Sports Medicine, Consumers Research Council of America (2008)
  • Top 70 Best Knee Surgeons in America, Becker's Hospital Review (2010)
  • US Olympic Committee Level III Physician, Volunteer Services, US Olympic Committee (2010-curr)
  • US Ski Team Physician, United States Ski and Snowboard Association (2005-curr)

Professional Education

  • Fellowship:Steadman Hawkins Sports Clinic Fellowship Training (2005) CO
  • Residency:UCLA Health Sciences (2004) CA
  • Board Certification: Sports Medicine, American Board of Orthopaedic Surgery (2010)
  • Subspecialty Certification, Sports Medicine, American Board of Orthopaedic Surgery (2011)
  • Board Certification: Orthopaedic Surgery, American Board of Orthopaedic Surgery (2007)
  • Internship:UCLA Health Sciences (1999) CA
  • Medical Education:University of Arizona College of Medicine (1998) AZ
  • MD, Steadman-Hawkins Sports Medicine, Sports Medicine (2005)
  • MD, UCLA, Orthopaedic Surgery (2004)
  • MD, University of Arizona, Medicine (1998)

Community and International Work

  • North American Representative for Exhange of Surgical Techniques with Europe

    Partnering Organization(s)

    American Orthopaedic Society of Sports Medicine/European Sports Medicine Society (ESSKA)

    Populations Served

    All of Europe



    Ongoing Project


    Opportunities for Student Involvement


Research & Scholarship

Current Research and Scholarly Interests


Current Tissue Engineering studies will focus on 3 main areas:

1. The ability to harvest stem cells from a patient, induce them into cartilage cells, and place them back into the patient during the same surgical procedure. Current surgical techniques require 1 surgery to harvest the cells, 2-3 weeks of laboratory processing, and another surgery to implant the cells. These techniques would revolutionize the use of stem cells in Orthopaedic Surgery.

2. Reconfigure the biologic matrices and processing to allow resurfacing of entire joint surfaces. This process would make current metal joint replacements obsolete and would allow the treatment of arthritis with the patients own stem cells.

3. Decipher the genetic induction code and ideal matrix for meniscal cartilage engineering. This would allow the production of meniscal cartilage grafts from the patients own stem cells.


1. Female ACL tears-The incidence of anterior cruciate ligament (ACL) rupture in female athletes is two to eight times that in males. Although many anatomical and biomechanical gender differences have been described, evidence is beginning to accumulate that female hormones are responsible for alterations in ligament laxity and strength. Relaxin is a peptide hormone found in the sera of pregnant and non-pregnant females, yet is not detectable in male serum. This hormone is thought to be responsible for connective tissue remodeling secondary to its collagenolytic effects.

We have identified relaxin receptors on the human female ACL. This supports the conclusion that relaxin, a hormone found in some non-pregnant females, may be responsible for the high incidence of ACL rupture in female athletes. We have also shown that the administration of relaxin to female guinea pigs results in ACL laxity and weakness. Recently, we have shown that relaxin levels in female intercollegiate athletes are higher in athletes who experience an ACL injury. We are currently developing a blocking antibody to administer to susceptible female athletes to hopefully decrease the ACL injury rate.

2. ACL tears and Arthritis-We are currently evaluating the body?s response to ACL injury, which may damage the articular cartilage in certain athletes. This may explain why certain athletes with ACL injury develop degenerative changes and early arthritis. Identification of cartilage injury patterns will help initiate early treatment intervention protocols to minimize the development of early arthritis in athletes.

3. New Surgical Techniques- We have created a new technique to perform revision (already had an ACL reconstruction, now it is torn again) ACL reconstruction during 1 surgical procedure. Previously, this procedure often required 2 surgeries: 1 to bone graft the previous bone defects and a second surgery 4 months later to reconstruct the ACL. This new procedure would save rehabilitation time and money and would mean less surgery for the patient. Final confirmatory animal studies are currently being performed.
4. Genetics- we are currently exploring possible genetic links to ACL injury using genome wide gene correlations of injuries in patient populations greater than 110,000.
5. ACL injury prevention- We have developed, and are currently testing, new methods for ACL prevention including: 1) New training programs using unstable surfaces, 2) Electronic Smartbraces, which sense the athletes movement patterns and give them feedback via vibration to stay away from dangerous positions.


This procedure involves concentrating growth factors from the patient's blood and injecting them at the site of injury to accelerate healing. We are currently investigating the use of PRP for tears to the patellar and quadriceps tendon, using a randomized controlled trial. We are also working on new formulations of PRP in the laboratory to improve clinical results.

Clinical Trials

  • Characterizing Knee Pain and Response to Surgery Using Local Biomarkers Recruiting

    The diagnosis and monitoring of clinically-significant pathologies of the knee remains challenging, and it is unknown why only some injuries become painful or respond to surgical intervention. The limitations of diagnostic magnetic resonance imaging result in arthroscopy that is not always beneficial. Elucidation of biochemical pathways underlying pain in this condition may aid patient selection for surgery and provide pharmacotherapeutic targets. Cytokines or a novel yet uncharacterized protein may be involved in pain following meniscus injury and diagnostic cytokine assay may help physicians differentiate patients that may benefit from arthroscopy from those that may not. Additionally, evaluating post-operative biochemical profiles may provide a method of monitoring surgical outcome and understanding post-operative continuation or remission of pain.

    View full details

  • Microfracture Versus Adipose Derived Stem Cells for the Treatment of Articular Cartilage Defects Recruiting

    The purpose of this study is to compare two biologic methods for the treatment of articular cartilage defects in the knee. The first method, microfracture, is the standard of care and is routinely used to recruit cells from the subchondral bone marrow to the site of cartilage loss. The second method is the application of adipose-derived stem cells (ADSCs) to the defect site. In theory, ADSCs on a collagen scaffold should enable the delivery of more specific progenitor cells to the site of injury, resulting in better regeneration and integration of articular cartilage at the site of a defect as compared to the microfracture method.

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  • The Effect of Adipose-Derived Stem Cells for Knee Osteoarthritis Recruiting

    The purpose of this study is to compare the clinical and functional outcomes of patients with mild to moderate arthroscopically confirmed osteoarthritis between the following two groups: 1. Partial fat pad harvest with Adipose-Derived Stem Cell (ADSC) transplantation with standard arthroscopic treatment consisting of: partial meniscectomy, cartilage stabilization, loose body removal and selective synovectomy. 2. Standard arthroscopic treatment (above) with out cell transplant.

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  • Treatment of Acute and Chronic Ligament and Tendon Injuries With Platelet Rich Plasma Recruiting

    Platelet rich plasma has been used in previous studies to stimulate faster healing of torn ligaments and tendons in order to help reduce pain and restore normal function. This study aims to prove that non-operative treatment of acute and chronic ligament and tendon injuries with platelet rich plasma will reduce the time needed for participants to heal these injuries and restore function. We are currently enrolling patients with PATELLAR TENDON INJURIES in the KNEE.

    View full details

  • Effects of Unloader Bracing in Clinical Outcome and Cartilage Physiology Following Microfracture of Chondral Defects Not Recruiting

    The study will examine clinical and radiographic outcomes of microfracture surgery (a common technique to address isolated areas of cartilage loss) in the knee used with or without unloader bracing. Randomly selected patients will wear an unloader brace, which is designed to take pressure off the area of the knee which underwent repair, for several weeks after surgery. Our hypothesis is that bracing may improve clinical and or radiographic outcomes. The surgery performed will be the same for all patients The length of follow up and schedule of post-operative MRI will be the same for all patients. The only difference in groups will be presence of absence of brace wear.

    Stanford is currently not accepting patients for this trial.

    View full details


2017-18 Courses


All Publications

  • Two Genetic Loci associated with Medial Collateral Ligament Injury. International journal of sports medicine Roos, A. K., Avins, A. L., Ahmed, M. A., Kleimeyer, J. P., Roos, T. R., Fredericson, M., Ioannidis, J. P., Dragoo, J. L., Kim, S. 2017


    Medial collateral ligament (MCL) injuries are a common knee injury, especially in competitive athletes. Identifying genetic loci associated with MCL injury could shed light on its etiology. A genome-wide association screen was performed using data from the Research Program in Genes, Environment and Health (RPGEH) including 1?572 cases of MCL injury and 100?931 controls. 2 SNPs (rs80351309 and rs6083471) showed an association with MCL injury at genome-wide significance (p<510(-8)) with moderate effects (odds ratios=2.12 and 1.57, respectively). For rs80351309, the genotypes were imputed with only moderate accuracy, so this SNP should be viewed with caution until its association with MCL injury can be validated. The SNPs rs80351309 and rs6083471 show a statistically significant association with MCL injury. It will be important to replicate this finding in future studies.

    View details for DOI 10.1055/s-0043-104853

    View details for PubMedID 28482362

  • Genome-wide association screens for Achilles tendon and ACL tears and tendinopathy PLOS ONE Kim, S. K., Roos, T. R., Roos, A. K., Kleimeyer, J. P., Ahmed, M. A., Goodlin, G. T., Fredericson, M., Ioannidis, J. P., Avins, A. L., Dragoo, J. L. 2017; 12 (3)


    Achilles tendinopathy or rupture and anterior cruciate ligament (ACL) rupture are substantial injuries affecting athletes, associated with delayed recovery or inability to return to competition. To identify genetic markers that might be used to predict risk for these injuries, we performed genome-wide association screens for these injuries using data from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort consisting of 102,979 individuals. We did not find any single nucleotide polymorphisms (SNPs) associated with either of these injuries with a p-value that was genome-wide significant (p<5x10-8). We found, however, four and three polymorphisms with p-values that were borderline significant (p<10-6) for Achilles tendon injury and ACL rupture, respectively. We then tested SNPs previously reported to be associated with either Achilles tendon injury or ACL rupture. None showed an association in our cohort with a false discovery rate of less than 5%. We obtained, however, moderate to weak evidence for replication in one case; specifically, rs4919510 in MIR608 had a p-value of 5.1x10-3 for association with Achilles tendon injury, corresponding to a 7% chance of false replication. Finally, we tested 2855 SNPs in 90 candidate genes for musculoskeletal injury, but did not find any that showed a significant association below a false discovery rate of 5%. We provide data containing summary statistics for the entire genome, which will be useful for future genetic studies on these injuries.

    View details for DOI 10.1371/journal.pone.0170422

    View details for Web of Science ID 000399174800001

    View details for PubMedID 28358823

  • Medial Patellofemoral Ligament Repair Versus Reconstruction for Recurrent Patellar Instability: Two-Year Results of an Algorithm-Based Approach. Orthopaedic journal of sports medicine Dragoo, J. L., Nguyen, M., Gatewood, C. T., Taunton, J. D., Young, S. 2017; 5 (3): 2325967116689465-?


    Patellar instability remains a challenging problem for both the patient and surgeon. Medial patellofemoral ligament (MPFL) repair has historically had poor results, and due to this, there is currently a trend toward reconstruction.This study was undertaken to investigate experience with repair versus reconstruction of the MPFL using a multifactorial treatment algorithm approach. Our hypothesis was that there will be no significant difference in outcome scores between patients in the MPFL repair and reconstruction groups.Cohort study; Level of evidence, 2.A total of 24 patients with recurrent (?2) lateral patellar dislocations were included. All had failed nonoperative treatment for more than 6 months, and all were observed for a minimum of 2 years. First, magnetic resonance imaging (MRI) was used to find the location of the MPFL tear. A tilt test was used to determine whether a lateral retinacular lengthening was required to allow the patella to have neutral tilt. If the MRI showed a tibial tubercle-trochlear groove (TT-TG) distance greater than 20 mm, a tibial tubercle osteotomy (TTO) was recommended. An MPFL reconstruction was performed if the entire ligament was inadequately visualized on MRI or if it was torn from both insertion sites. Failure was defined as recurrent lateral patellar instability after surgery. As a secondary outcome measure, Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm score, and Tegner score were calculated.All patients were evaluated with a mean follow-up of 51 months (range, 25-79 months). Sixteen patients initially underwent MPFL repair, 8 underwent reconstruction, and 3 also underwent TTO. MPFL reconstructions were performed in all patients who underwent TTO. One MPFL repair was to the anatomic femoral origin and 15 were to the patellar insertion corresponding to the site of tearing on MRI. A lateral retinacular lengthening was performed in 21 patients. There was 1 failure in the repair group (6%) and none in the reconstruction group. However, the patient who failed had a TT-TG distance of 26 mm but refused a TTO. She subsequently underwent revision with a TTO and MPFL reconstruction and did not have any further instability events. There were no significant differences between groups for any of the secondary outcome scores.Using an algorithm-based approach, MPFL repair or reconstruction may lead to clinically acceptable results at 2-year follow-up.

    View details for DOI 10.1177/2325967116689465

    View details for PubMedID 28451595

  • The Use of Platelet-Rich and Platelet-Poor Plasma to Enhance Differentiation of Skeletal Myoblasts: Implications for the Use of Autologous Blood Products for Muscle Regeneration AMERICAN JOURNAL OF SPORTS MEDICINE Miroshnychenko, O., Chang, W., Dragoo, J. L. 2017; 45 (4): 945-953
  • Biomechanical Effects of an Injury Prevention Program in Preadolescent Female Soccer Athletes AMERICAN JOURNAL OF SPORTS MEDICINE Thompson, J. A., Tran, A. A., Gatewood, C. T., Shultz, R., Silder, A., Delp, S. L., Dragoo, J. L. 2017; 45 (2): 294-301
  • The efficacy of post-operative devices following knee arthroscopic surgery: a systematic review KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY Gatewood, C. T., Tran, A. A., Dragoo, J. L. 2017; 25 (2): 501-516
  • CD24 enrichment protects while its loss increases susceptibility of juvenile chondrocytes towards inflammation ARTHRITIS RESEARCH & THERAPY Lee, J., Smeriglio, P., Dragoo, J., Maloney, W. J., Bhutani, N. 2016; 18


    Diseases associated with human cartilage, including rheumatoid arthritis (RA) and osteoarthritis (OA) have manifested age, mechanical stresses and inflammation as the leading risk factors. Although inflammatory processes are known to be upregulated upon aging, we sought to gain a molecular understanding of how aging affects the tissue-specific response to inflammation. In this report, we explored the role of cluster of differentiation 24 (CD24) in regulating differential inflammatory responses in juvenile and adult human chondrocytes.Differential cell-surface CD24 expression was assessed in juvenile and adult chondrocytes along with human induced pluripotent stem cell (hiPSC)-derived neonatal chondrocytes through gene expression and fluorescence-activated cell sorting (FACS) analyses. Loss of function of CD24 was achieved through silencing in chondrocytes and the effects on the response to inflammatory cues were assessed through gene expression and NF?B activity.CD24 expression in chondrocytes caused a differential response to cytokine-induced inflammation, with the CD24(high) juvenile chondrocytes being resistant to IL-1 treatment as compared to CD24(low) adult chondrocytes. CD24 protects from inflammatory response by reducing NF?B activation, as an acute loss of CD24 via silencing led to an increase in NF?B activation. Moreover, the loss of CD24 in chondrocytes subsequently increased inflammatory and catabolic gene expression both in the absence and presence of IL-1.We have identified CD24 as a novel regulator of inflammatory response in cartilage that is altered during development and aging and could potentially be therapeutic in RA and OA.

    View details for DOI 10.1186/s13075-016-1183-y

    View details for Web of Science ID 000390276900003

    View details for PubMedID 27955675

    View details for PubMedCentralID PMC5153697

  • The effect of foot landing position on biomechanical risk factors associated with anterior cruciate ligament injury. Journal of experimental orthopaedics Tran, A. A., Gatewood, C., Harris, A. H., Thompson, J. A., Dragoo, J. L. 2016; 3 (1): 13-?


    Identification of biomechanical risk factors associated with anterior cruciate ligament (ACL) injury can facilitate injury prevention. The purpose of this study is to investigate the effects of three foot landing positions, "toe-in", "toe-out" and "neutral", on biomechanical risk factors for ACL injury in males and females. The authors hypothesize that 1) relative to neutral, the toe-in position increases the biomechanical risk factors for ACL injury, 2) the toe-out position decreases these biomechanical risk factors, and 3) compared to males, females demonstrate greater changes in lower extremity biomechanics with changes in foot landing position.Motion capture data on ten male and ten female volunteers aged 20-30 years (26.4??2.50) were collected during double-leg jump landing activities. Subjects were asked to land on force plates and target one of three pre-templated foot landing positions: 0 ("neutral"), 30 internal rotation ("toe-in"), and 30 external rotation ("toe-out") along the axis of the anatomical sagittal plane. A mixed-effects ANOVA and pairwise Tukey post-hoc comparison were used to detect differences in kinematic and kinetic variables associated with biomechanical risk factors of ACL injury between the three foot landing positions.Relative to neutral, landing in the toe-in position increased peak hip adduction, knee internal rotation angles and moments (p?

    View details for DOI 10.1186/s40634-016-0049-1

    View details for PubMedID 27315816

  • The Use of Platelet-Rich and Platelet-Poor Plasma to Enhance Differentiation of Skeletal Myoblasts. American journal of sports medicine Miroshnychenko, O., Chang, W., Dragoo, J. L. 2016: 363546516677547-?


    Platelet-rich plasma (PRP) has been used to augment tissue repair and regeneration after musculoskeletal injury. However, there is increasing clinical evidence that PRP does not show a consistent clinical effect. Purpose/Hypothesis: This study aimed to compare the effects of the following non-neutrophil-containing (leukocyte-poor) plasma fractions on human skeletal muscle myoblast (HSMM) differentiation: (1) PRP, (2) modified PRP (Mod-PRP), in which transforming growth factor ?1 (TGF-?1) and myostatin (MSTN) were depleted, and (3) platelet-poor plasma (PPP). The hypothesis was that leukocyte-poor PRP would lead to myoblast proliferation (not differentiation), whereas certain modifications of PRP preparations would increase myoblast differentiation, which is necessary for skeletal muscle regeneration.Controlled laboratory study.Blood from 7 human donors was individually processed to simultaneously create leukocyte-poor fractions: PRP, Mod-PRP, PPP, and secondarily spun PRP and Mod-PRP (PRPss and Mod-PRPss, respectively). Mod-PRP was produced by removing TGF-?1 and MSTN from PRP using antibodies attached to sterile beads, while a second-stage centrifugal spin of PRP was performed to remove platelets. The biologics were individually added to cell culture groups. Analysis for induction into myoblast differentiation pathways included Western blot analysis, reverse-transcription polymerase chain reaction, and immunohistochemistry, as well as confocal microscopy to assess polynucleated myotubule formation.HSMMs cultured with PRP showed an increase in proliferation but no evidence of differentiation. Western blot analysis confirmed that MSTN and TGF-?1 could be decreased in Mod-PRP using antibody-coated beads, but this modification mildly improved myoblast differentiation. However, cell culture with PPP, PRPss, and Mod-PRPss led to a decreased proliferation rate but a significant induction of myoblast differentiation verified by increased multinucleated myotubule formation and myosin heavy chain expression (mean 8-fold change in mRNA level; P < .05), which was comparable with 2% horse serum, the positive control.PPP and leukocyte-poor PRP preparations subjected to a second spin to remove the platelets led to induction of myoblast cells into the muscle differentiation pathway, whereas unmodified leukocyte-poor PRP led to myoblast proliferation.These results indicate that traditionally formulated PRP may not be appropriate to induce muscle regeneration. Laboratory evidence suggests that PPP or non-neutrophil-containing PRPss, subjected to an additional spin to remove platelets, should be used to stimulate myoblast differentiation, which is necessary for skeletal muscle regeneration. Clinical studies will be required to confirm the effect of these biologics on muscle regeneration.

    View details for DOI 10.1177/0363546516677547

    View details for PubMedID 28027451

  • Biomechanical Effects of an Injury Prevention Program in Preadolescent Female Soccer Athletes. American journal of sports medicine Thompson, J. A., Tran, A. A., Gatewood, C. T., Shultz, R., Silder, A., Delp, S. L., Dragoo, J. L. 2016


    Anterior cruciate ligament (ACL) injuries are common, and children as young as 10 years of age exhibit movement patterns associated with an ACL injury risk. Prevention programs have been shown to reduce injury rates, but the mechanisms behind these programs are largely unknown. Few studies have investigated biomechanical changes after injury prevention programs in children.To investigate the effects of the F-MARC 11+ injury prevention warm-up program on changes to biomechanical risk factors for an ACL injury in preadolescent female soccer players. We hypothesized that the primary ACL injury risk factor of peak knee valgus moment would improve after training. In addition, we explored other kinematic and kinetic variables associated with ACL injuries.Controlled laboratory study.A total of 51 female athletes aged 10 to 12 years were recruited from soccer clubs and were placed into an intervention group (n = 28; mean [SD] age, 11.8 0.8 years) and a control group (n = 23; mean age, 11.2 0.6 years). The intervention group participated in 15 in-season sessions of the F-MARC 11+ program (2 times/wk). Pre- and postseason motion capture data were collected during preplanned cutting, unanticipated cutting, double-leg jump, and single-leg jump tasks. Lower extremity joint angles and moments were estimated using OpenSim, a biomechanical modeling system.Athletes in the intervention group reduced their peak knee valgus moment compared with the control group during the double-leg jump (mean [standard error of the mean] pre- to posttest change, -0.57 0.27 %BWHT vs 0.25 0.25 %BWHT, respectively; P = .034). No significant differences in the change in peak knee valgus moment were found between the groups for any other activity; however, the intervention group displayed a significant pre- to posttest increase in peak knee valgus moment during unanticipated cutting (P = .044). Additional analyses revealed an improvement in peak ankle eversion moment after training during preplanned cutting (P = .015), unanticipated cutting (P = .004), and the double-leg jump (P = .016) compared with the control group. Other secondary risk factors did not significantly improve after training, although the peak knee valgus angle improved in the control group compared with the intervention group during unanticipated cutting (P = .018).The F-MARC 11+ program may be effective in improving some risk factors for an ACL injury during a double-leg jump in preadolescent athletes, most notably by reducing peak knee valgus moment.This study provides motivation for enhancing injury prevention programs to produce improvement in other ACL risk factors, particularly during cutting and single-leg tasks.

    View details for PubMedID 27793803

  • The efficacy of post-operative devices following knee arthroscopic surgery: a systematic review. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA Gatewood, C. T., Tran, A. A., Dragoo, J. L. 2016: -?


    There is a wide array of device modalities available for post-operative treatment following arthroscopic knee surgery; however, it remains unclear which types and duration of modality are the most effective. This systematic review aimed to investigate the efficacy of device modalities used following arthroscopic knee surgery.A systematic search of the literature was performed on: PubMed; Scopus; MEDLINE; EMBASE; PEDro; SportDiscus; and CINAHL databases (1995-2015) for clinical trials using device modalities following arthroscopic knee surgery: cryotherapy, continuous passive motion (CPM), neuromuscular electrical stimulation (NMES), surface electromyographic (sEMG) biofeedback and shockwave therapy (ESWT). Only level 1 and 2 studies were included and the methodological quality of studies was evaluated using Physiotherapy Evidence Database (PEDro) scores. Outcome measures included: muscle strength, range of motion, swelling, blood loss, pain relief, narcotic use, knee function evaluation and scores, patient satisfaction and length of hospital stay.Twenty-five studies were included in this systematic review, nineteen of which found a significant difference in outcomes. For alleviating pain and decreasing narcotic consumption following arthroscopic knee surgery, cryocompression devices are more effective than traditional icing alone, though not more than compression alone. CPM does not affect post-operative outcomes. sEMG biofeedback and NMES improve quadriceps strength and overall knee functional outcomes following knee surgery. There is limited evidence regarding the effects of ESWT.Cryotherapy, NMES and sEMG are recommended for inclusion into rehabilitation protocols following arthroscopic knee surgery to assist with pain relief, recovery of muscle strength and knee function, which are all essential to accelerate recovery. CPM is not warranted in post-operative protocols following arthroscopic knee surgery because of its limited effectiveness in returning knee range of motion, and additional studies are required to investigate the effects of ESWT.II.

    View details for PubMedID 27695905

  • The Intracellular Effect of Relaxin on Female Anterior Cruciate Ligament Cells. American journal of sports medicine Konopka, J. A., DeBaun, M. R., Chang, W., Dragoo, J. L. 2016; 44 (9): 2384-2392


    Female collegiate athletes with serum relaxin concentrations above 6.0 pg/mL have been shown to have more than 4 times increased risk for anterior cruciate ligament (ACL) tears. However, the intracellular effect of relaxin on ACL cells has not been elucidated.The hypotheses were that relaxin binding to receptors on female ACL cells will result in (1) an increase in matrix metalloproteinase (MMP) and decrease in tissue inhibitor of metalloproteinase (TIMP) gene expression, (2) a decrease in collagen and alpha smooth muscle actin (?SMA) expression, (3) inhibition of transforming growth factor ?1 (TGF?1)-induced fibrosis, and (4) an increase in cyclic adenosine 3',5'-monophosphate (cAMP) production and that these changes will not be observed in male ACL cells.Controlled laboratory study.Ligament cells from ACL tissue were isolated from 7 male and 7 female human donors and expanded in vitro. The cells were incubated with escalating concentrations of relaxin-2, as well as with TGF?1 or 17?-estradiol in certain groups. Cells were then lysed and analyzed for MMP1 (collagenase-1), MMP3 (stromelysin-1), MMP13 (collagenase-3), TIMP1, type I collagen, type III collagen, and/or ?SMA mRNA expression using quantitative real-time polymerase chain reaction. Intracellular cAMP levels were assessed via an enzyme-linked immunoassay.ACL cells primed with estrogen and treated with 10 ng/mL and 100 ng/mL relaxin illustrated increased MMP1 expression (P = .012 and .006, respectively) and MMP3 expression (P = .005 and .001, respectively). Treatment with 100 ng/mL relaxin decreased ?SMA expression (P = .001). When ACL tissue isolated from female donors with a history of oral contraceptive use was excluded from the analysis, 100 ng/mL of relaxin decreased type I collagen (P = .005) and type III collagen (P = .028) expression in cells primed with estrogen. Relaxin exhibited no significant effect on male-derived ACL cells.Relaxin-2 significantly upregulated intracellular processes in human female ACL cells, but no effect was observed in male cells. Relaxin increased MMP (MMP1 and MMP3) and decreased ?SMA and type I and III collagen expression, which may act to alter the structural integrity of the ACL tissue over time.Female athletes with higher circulating relaxin levels may be more susceptible to ACL injury.

    View details for DOI 10.1177/0363546516646374

    View details for PubMedID 27245459

  • AAOS Research Symposium Updates and Consensus: Biologic Treatment of Orthopaedic Injuries JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LaPrade, R. F., Dragoo, J. L., Koh, J. L., Murray, I. R., Geeslin, A. G., Chu, C. R. 2016; 24 (7): E62-E78


    Strategies that seek to enhance musculoskeletal tissue regeneration and repair by modulating the biologic microenvironment at the site of injury have considerable therapeutic potential. Current and emerging biologic approaches include the use of growth factors, platelet-rich plasma, stem cell therapy, and scaffolds. The American Academy of Orthopaedic Surgeons hosted a research symposium in November 2015 to review the current state-of-the-art biologic treatments of articular cartilage, muscle, tendon, and bone injuries and identify knowledge gaps related to these emerging treatments. This review outlines the findings of the symposium and summarizes the consensus reached on how best to advance research on biologic treatment of orthopaedic injuries.

    View details for DOI 10.5435/JAAOS-D-16-00086

    View details for Web of Science ID 000383728900002

    View details for PubMedID 27227987

  • Identification of Human Juvenile Chondrocyte-Specific Factors that Stimulate Stem Cell Growth TISSUE ENGINEERING PART A Taylor, S. E., Lee, J., Smeriglio, P., Razzaque, A., Smith, R. L., Dragoo, J. L., Maloney, W. J., Bhutani, N. 2016; 22 (7-8): 645-653


    Although regeneration of human cartilage is inherently inefficient, age is an important risk factor for osteoarthritis. Recent reports have provided compelling evidence that juvenile chondrocytes (from donors below 13 years of age) are more efficient at generating articular cartilage as compared to adult chondrocytes. However, the molecular basis for such a superior regenerative capability is not understood. To identify the cell-intrinsic differences between juvenile and adult cartilage, we have systematically profiled global gene expression changes between a small cohort of human neonatal/juvenile and adult chondrocytes. No such study is available for human chondrocytes although young and old bovine and equine cartilage have been recently profiled. Our studies have identified and validated new factors enriched in juvenile chondrocytes as compared to adult chondrocytes including secreted extracellular matrix factors chordin-like 1 (CHRDL1) and microfibrillar-associated protein 4 (MFAP4). Network analyses identified cartilage development pathways, epithelial-mesenchymal transition, and innate immunity pathways to be overrepresented in juvenile-enriched genes. Finally, CHRDL1 was observed to aid the proliferation and survival of bone marrow-derived human mesenchymal stem cells (hMSC) while maintaining their stem cell potential. These studies, therefore, provide a mechanism for how young cartilage factors can potentially enhance stem cell function in cartilage repair.

    View details for DOI 10.1089/ten.tea.2015.0366

    View details for Web of Science ID 000374761600007

    View details for PubMedID 26955889

  • The Effect of Intra-articular Corticosteroids on Articular Cartilage: A Systematic Review. Orthopaedic journal of sports medicine Wernecke, C., Braun, H. J., Dragoo, J. L. 2015; 3 (5): 2325967115581163-?


    Intra-articular (IA) corticosteroid therapy has been used for the treatment of inflammation and pain in the knee since the 1950s.To review the current literature on the effects of IA corticosteroids on articular cartilage.Systematic review.A MEDLINE and SCOPUS database search was performed, and studies were selected for basic science and clinical trial research on corticosteroids with direct outcome measures of cartilage health. Preliminary searches yielded 1929 articles, and final analysis includes 40 studies.Methylprednisolone, dexamethasone, hydrocortisone, betamethasone, prednisolone, and triamcinolone were reported to display dose-dependent deleterious effects on cartilage morphology, histology, and viability in both in vitro and in vivo models. The beneficial animal in vivo effects of methylprednisolone, hydrocortisone, and triamcinolone occurred at low doses (usually <2-3 mg/dose or 8-12 mg/cumulative total dose in vivo), at which increased cell growth and recovery from damage was observed; the single human clinical trial indicated a beneficial effect of triamcinolone. However, at higher doses (>3 mg/dose or 18-24 mg/cumulative total dose in vivo), corticosteroids were associated with significant gross cartilage damage and chondrocyte toxicity. Dose and time dependency of corticosteroid chondrotoxicity was supported in the in vitro results, however, without clear dose thresholds.Corticosteroids have a time- and dose-dependent effect on articular cartilage, with beneficial effects occurring at low doses and durations and detrimental effects at high doses and durations. Clinically, beneficial effects are supported for IA administration, but the lowest efficacious dose should be used.

    View details for DOI 10.1177/2325967115581163

    View details for PubMedID 26674652

  • Differences in ACL biomechanical risk factors between field hockey and lacrosse female athletes KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY Braun, H. J., Shultz, R., Malone, M., Leatherwood, W. E., Silder, A., Dragoo, J. L. 2015; 23 (4): 1065-1070


    Previous investigations have revealed a greater incidence of anterior cruciate ligament (ACL) injuries in female lacrosse versus field hockey players. Lacrosse is played in an upright posture with overhead throwing and catching, while field hockey is almost exclusively played in a crouched, forward-flexed position. Biomechanical factors, including decreased knee, hip, and trunk flexion angles, have been identified as risk factors for ACL injury. The purpose of this study was to assess ACL biomechanical risk factors in female field hockey and lacrosse players to determine whether sport-specific posture might contribute to the increased incidence of ACL injury observed in lacrosse athletes.Thirty-one Division I NCAA females from field hockey and lacrosse completed four tasks, three times per leg: bilateral drop jump, single-leg drop jump (SDJ), single-leg jump onto a Bosu ball (SDB), and a 45 anticipated cut. Kinematic and force plate data were used to evaluate knee flexion angle, knee adduction moment, hip flexion angle, and trunk flexion and sway angles. Muscle activity of the lateral hamstrings and vastus lateralis was used to estimate peak hamstring activity and the quadriceps/hamstring ratio at the time of peak quadriceps activity (co-contraction ratio).During the SDJ and SDB, peak knee flexion angles were greater in field hockey compared with lacrosse. During cutting, field hockey players were more flexed at the trunk and had greater trunk sway, compared with the lacrosse players. No significant difference was observed for the co-contraction ratio for any of the tasks.Decreased knee flexion angle during landing, consistent with sport-specific playing postures, may contribute to the higher incidence of ACL injury in lacrosse players relative to field hockey. Sport-specific training injury prevention programmes may benefit from considering these differences between specialized athletes.II.

    View details for DOI 10.1007/s00167-014-2873-0

    View details for Web of Science ID 000351611700021

    View details for PubMedID 24493257

  • Unstable Surface Improves Quadriceps:Hamstring Co-contraction for Anterior Cruciate Ligament Injury Prevention Strategies. Sports health Shultz, R., Silder, A., Malone, M., Braun, H. J., Dragoo, J. L. 2015; 7 (2): 166-171


    Increasing quadriceps:hamstring muscular co-contraction at the knee may reduce the risk of anterior cruciate ligament (ACL) injury. The purpose of this investigation was to examine muscle activation in the quadriceps and hamstrings and peak kinematics of the knee, hip, and trunk when performing a single-leg drop (SLD) on to a Bosu ball (unstable surface) compared with on to the floor (stable surface).(1) The SLD on an unstable surface would lower the quadriceps to hamstrings electromyographic (EMG) activation ratio (Q:H EMG activation ratio) compared with being performed on the floor. (2) Lower Q:H EMG activation ratio would be caused by a relative increase in hamstring activation, with no significant change in quadriceps activation.Controlled laboratory study.Thirty-nine Division I National Collegiate Athletic Association (NCAA) female athletes performed 3 SLDs per leg onto a Bosu ball and onto the floor. Muscle activity of the vastus lateralis and lateral hamstrings were used to estimate peak quadriceps and hamstring activation, along with the Q:H EMG activation ratio. Kinematic measures at the knee, hip, and trunk were also estimated. Differences between landings were assessed using a 2-level analysis of variance (limb and surface).The maximum Q:H EMG activation ratio was significantly reduced when athletes performed an SLD onto the Bosu ball (20%, P < 0.001) compared with the floor. Peak hamstring activity was higher when athletes landed on a Bosu ball (18% higher, P = 0.029) compared with when they landed on the floor.Compared with landing on the floor (a stable surface), landing on a Bosu ball (unstable surface) changed the athlete's co-contraction at the knee and increased hamstring activity. However, landing on a Bosu ball also decreased the athlete's knee flexion, which was an undesired effect.These findings highlight the potential utility of unstable surfaces as a training tool to reduce the risk of ACL injury in female athletes.

    View details for DOI 10.1177/1941738114565088

    View details for PubMedID 25984263

  • Collagen VI Enhances Cartilage Tissue Generation by Stimulating Chondrocyte Proliferation. Tissue engineering. Part A Smeriglio, P., Dhulipala, L., Lai, J. H., Goodman, S. B., Dragoo, J. L., Smith, R. L., Maloney, W. J., Yang, F., Bhutani, N. 2015; 21 (3-4): 840-849


    Regeneration of human cartilage is inherently inefficient. Current cell-based approaches for cartilage repair, including autologous chondrocytes, are limited by the paucity of cells, associated donor site morbidity, and generation of functionally inferior fibrocartilage rather than articular cartilage. Upon investigating the role of collagen VI (Col VI), a major component of the chondrocyte pericellular matrix (PCM), we observe that soluble Col VI stimulates chondrocyte proliferation. Interestingly, both adult and osteoarthritis chondrocytes respond to soluble Col VI in a similar manner. The proliferative effect is, however, strictly due to the soluble Col VI as no proliferation is observed upon exposure of chondrocytes to immobilized Col VI. Upon short Col VI treatment in 2D monolayer culture, chondrocytes maintain high expression of characteristic chondrocyte markers like Col2a1, agc, and Sox9 whereas the expression of the fibrocartilage marker Collagen I (Col I) and of the hypertrophy marker Collagen X (Col X) is minimal. Additionally, Col VI-expanded chondrocytes show a similar potential to untreated chondrocytes in engineering cartilage in 3D biomimetic hydrogel constructs. Our study has, therefore, identified soluble Col VI as a biologic that can be useful for the expansion and utilization of scarce sources of chondrocytes, potentially for autologous chondrocyte implantation. Additionally, our results underscore the importance of further investigating the changes in chondrocyte PCM with age and disease and the subsequent effects on chondrocyte growth and function.

    View details for DOI 10.1089/ten.TEA.2014.0375

    View details for PubMedID 25257043

  • The Effect of Donor Age on Structural and Mechanical Properties of Allograft Tendons AMERICAN JOURNAL OF SPORTS MEDICINE Swank, K. R., Behn, A. W., Dragoo, J. L. 2015; 43 (2): 453-459


    Allograft tendons are commonly used in surgical ligament reconstruction. While it is commonly accepted that donor age will affect mechanical properties of graft tissue, the apparent age threshold is unknown.Donor age will significantly influence the structural and mechanical properties of tibialis posterior allograft tendons.Controlled laboratory study.A total of 550 allograft posterior tibialis tendons were examined. Linear stiffness, ultimate tensile force, ultimate displacement, tensile modulus, ultimate tensile strength, and ultimate tensile strain were calculated for specimens from donors in each of 6 age groups: 15-29, 30-39, 40-49, 50-59, 60-69, and 70-79 years. Both first- and second-order polynomial regressions were performed to determine the correlation between structural and mechanical properties and age. Welch analyses of variance with Games-Howell post hoc tests were performed to facilitate comparisons among age groups.All parameters displayed a weak correlation with age, with the highest R (2) term being 0.063 for ultimate tensile strength. Linear stiffness, ultimate tensile force, and tensile modulus displayed almost no correlation with age. Ultimate tensile strength increased slightly with age up to 40-49 years and then decreased with further increases in age. Slight decreases in ultimate displacement and ultimate tensile strain were observed with increasing age. Numerous statistically significant differences were observed between age groups for each outcome parameter; however, the magnitudes of the differences between age groups are relatively small (<15%) for all outcome parameters.Age explained at most 6% of the variation in structural and mechanical properties of tibialis posterior allograft tendons.Posterior tibialis tendons from all age groups displayed structural properties superior to the native anterior cruciate ligament, with higher stiffness and ultimate force, and less displacement to failure. Although statistically significant differences in structural and mechanical properties were observed between age groups, the magnitudes of the differences are small and most likely not clinically relevant. The age of the donor will not likely affect the suitability of a graft for use in surgical reconstruction.

    View details for DOI 10.1177/0363546514557246

    View details for Web of Science ID 000350470600026

    View details for PubMedID 25404616

  • The effect of relaxin on the musculoskeletal system SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS Dehghan, F., Haerian, B. S., Muniandy, S., Yusof, A., Dragoo, J. L., Salleh, N. 2014; 24 (4): E220-E229

    View details for DOI 10.1111/sms.12149

    View details for Web of Science ID 000339716800001

  • The effect of relaxin on the musculoskeletal system. Scandinavian journal of medicine & science in sports Dehghan, F., Haerian, B. S., Muniandy, S., Yusof, A., Dragoo, J. L., Salleh, N. 2014; 24 (4): e220-9


    Relaxin is a hormone structurally related to insulin and insulin-like growth factor, which exerts its regulatory effect on the musculoskeletal and other systems through binding to its receptor in various tissues, mediated by different signaling pathways. Relaxin alters the properties of cartilage and tendon by activating collagenase. This hormone is also involved in bone remodeling and healing of injured ligaments and skeletal muscle. In this review, we have summarized the literature on the effect of relaxin in musculoskeletal system to provide a broad perspective for future studies in this field.

    View details for DOI 10.1111/sms.12149

    View details for PubMedID 24283470

  • The Effect of Platelet-Rich Plasma Formulations and Blood Products on Human Synoviocytes Implications for Intra-articular Injury and Therapy AMERICAN JOURNAL OF SPORTS MEDICINE Braun, H. J., Kim, H. J., Chu, C. R., Dragoo, J. L. 2014; 42 (5): 1204-1210


    The effect of platelet-rich plasma (PRP) on chondrocytes has been studied in cell and tissue culture, but considerably less attention has been given to the effect of PRP on synoviocytes. Fibroblast-like synoviocytes (FLS) compose 80% of the normal human synovium and produce cytokines and matrix metalloproteinases that can mediate cartilage catabolism.To compare the effects of leukocyte-rich PRP (LR-PRP), leukocyte-poor PRP (LP-PRP), red blood cell (RBC) concentrate, and platelet-poor plasma (PPP) on human FLS to determine whether leukocyte and erythrocyte concentrations of PRP formulations differentially affect the production of inflammatory mediators.Controlled laboratory study.Peripheral blood was obtained from 4 donors and processed to create LR-PRP, LP-PRP, RBCs, and PPP. Human synoviocytes were cultured for 96 hours with the respective experimental conditions using standard laboratory conditions. Cell viability and inflammatory mediator production were then evaluated.Treatment with LR-PRP resulted in significantly greater synoviocyte death (4.9% 3.1%) compared with LP-PRP (0.72% 0.70%; P = .035), phosphate-buffered saline (PBS) (0.39% 0.27%; P = .018), and PPP (0.26% 0.30%; P = .013). Synoviocytes treated with RBC concentrate demonstrated significantly greater cell death (12.5% 6.9%) compared with PBS (P < .001), PPP (P < .001), LP-PRP (P < .001), and LR-PRP (4.9% 3.1%; P < .001). Interleukin (IL)-1? content was significantly higher in cultures treated with LR-PRP (1.53 0.86 pg/mL) compared with those treated with PBS (0.22 0.295 pg/mL; P < .001), PPP (0.11 0.179 pg/mL; P < .001), and RBCs (0.64 0.58 pg/mL; P = .001). IL-6 content was also higher with LR-PRP (32,097.82 22,844.300 pg/mL) treatment in all other groups (P < .001). Tumor necrosis factor-? levels were greatest in LP-PRP (9.97 3.110 pg/mL), and this was significantly greater compared with all other culture conditions (P < .001). Interferon-? levels were greatest in RBCs (64.34 22.987 pg/mL) and significantly greater than all other culture conditions (P < .001).Treatment of synovial cells with LR-PRP and RBCs resulted in significant cell death and proinflammatory mediator production.Clinicians should consider using leukocyte-poor, RBC-free formulations of PRP when administering intra-articularly.

    View details for DOI 10.1177/0363546514525593

    View details for Web of Science ID 000335567700024

    View details for PubMedID 24634448

  • Platelet-rich plasma as a treatment for patellar tendinopathy: a double-blind, randomized controlled trial. American journal of sports medicine Dragoo, J. L., Wasterlain, A. S., Braun, H. J., Nead, K. T. 2014; 42 (3): 610-618


    BACKGROUND:Previous studies have shown improvement in patellar tendinopathy symptoms after platelet-rich plasma (PRP) injections, but no randomized controlled trial has compared PRP with dry needling (DN) for this condition. PURPOSE:To compare clinical outcomes in patellar tendinopathy after a single ultrasound-guided, leukocyte-rich PRP injection versus DN. STUDY DESIGN:Randomized controlled trial; Level of evidence, 1. METHODS:A total of 23 patients with patellar tendinopathy on examination and MRI who had failed nonoperative treatment were enrolled and randomized to receive ultrasound-guided DN alone (DN group; n = 13) or with injection of leukocyte-rich PRP (PRP group; n = 10), along with standardized eccentric exercises. Patients and the physician providing follow-up care were blinded. Participants completed patient-reported outcome surveys before and at 3, 6, 9, 12, and ?26 weeks after treatment during follow-up visits. The primary outcome measure was the Victorian Institute of Sports Assessment (VISA) score for patellar tendinopathy at 12 weeks, and secondary measures included the visual analog scale (VAS) for pain, Tegner activity scale, Lysholm knee scale, and Short Form (SF-12) questionnaire at 12 and ?26 weeks. Results were analyzed using 2-tailed paired and unpaired t tests. Patients who were dissatisfied at 12 weeks were allowed to cross over into a separate unblinded arm. RESULTS:At 12 weeks after treatment, VISA scores improved by a mean standard deviation of 5.2 12.5 points (P = .20) in the DN group (n = 12) and by 25.4 23.2 points (P = .01) in the PRP group (n = 9); at ?26 weeks, the scores improved by 33.2 14.0 points (P = .001) in the DN group (n = 9) and by 28.9 25.2 points (P = .01) in the PRP group (n = 7). The PRP group had improved significantly more than the DN group at 12 weeks (P = .02), but the difference between groups was not significant at ?26 weeks (P = .66). Lysholm scores were not significantly different between groups at 12 weeks (P = .81), but the DN group had improved significantly more than the PRP group at ?26 weeks (P = .006). At 12 weeks, 3 patients in the DN group failed treatment and subsequently crossed over into the PRP group. These patients were excluded from the primary ?26-week analysis. There were no treatment failures in the PRP group. No adverse events were reported. Recruitment was stopped because interim analysis demonstrated statistically significant and clinically important results. CONCLUSION:A therapeutic regimen of standardized eccentric exercise and ultrasound-guided leukocyte-rich PRP injection with DN accelerates the recovery from patellar tendinopathy relative to exercise and ultrasound-guided DN alone, but the apparent benefit of PRP dissipates over time.

    View details for DOI 10.1177/0363546513518416

    View details for PubMedID 24481828

  • The effect of resveratrol on normal and osteoarthritic chondrocyte metabolism BONE & JOINT RESEARCH Kim, H. J., Braun, H. J., Dragoo, J. L. 2014; 3 (3): 51-59


    Resveratrol is a polyphenolic compound commonly found in the skins of red grapes. Sirtuin1 (SIRT1) is a human gene that is activated by resveratrol and has been shown to promote longevity and boost mitochondrial metabolism. We examined the effect of resveratrol on normal and osteoarthritic (OA) human chondrocytes.Normal and OA chondrocytes were incubated with various concentrations of resveratrol (1M, 10 M, 25 M and 50 M) and cultured for 24, 48 or 72 hours or for six weeks. Cell proliferation, gene expression, and senescence were evaluated.SIRT1 was significantly upregulated in normal chondrocytes with resveratrol concentrations of 25 M and 50 M on both two- (2D) (both p = 0.001) and three-dimensional (3D) cultures (p=0.008 and 0.001, respectively). It was significantly upregulated in OA chondrocytes treated with 10 M, 25 M and 50 M resveratrol on 2D cultures (p = 0.036, 0.002 and 0.001, respectively) and at 50 M concentration on 3D cultures (p = 0.001). At 72hours, the expression of collagen (COL)-10, aggrecan (AGG), and runt-related transcription factor 2 (RUNX2) was significantly greater in both 25 M (p = 0.011, 0.006 and 0.015, respectively) and 50 M (p=0.019, 0.004 and 0.002, respectively) resveratrol-treated normal chondrocyte cultures. In OA chondrocytes, expression of COL10 and RUNX2 was significantly greater in 25 M (p = 0.004 and 0.024) and 50 M (p = 0.004 and 0.019) cultures at 72 hours on 3D cultures.At concentrations of 25 M and/or 50 M, resveratrol treatment significantly upregulates SIRT1 gene expression in normal and osteoarthritic chondrocytes. Resveratrol induces chondrocytes into a hypertrophic state through upregulation of COL1, COL10, and RUNX2. Cite this article: Bone Joint Res 2014;3:51-9.

    View details for DOI 10.1302/2046-3758.33.2000226

    View details for Web of Science ID 000344762700002

    View details for PubMedID 24615710

  • Incidence and Risk Factors for Turf Toe Injuries in Intercollegiate Football: Data From the National Collegiate Athletic Association Injury Surveillance System FOOT & ANKLE INTERNATIONAL George, E., Harris, A. H., Dragoo, J. L., Hunt, K. J. 2014; 35 (2): 108-115


    Turf toe is the general term for a sprain of the first metatarsophalangeal (MTP) joint complex. Previously attributed to shoe design and artificial turf, the incidence of turf toe injury has been thought to decline with the advent of newer turf designs. However, the current incidence and epidemiology remain unknown as the majority of the literature consists of small series and addresses diagnosis and treatment rather than epidemiology and prevention.We examined data from the NCAA's Injury Surveillance System (ISS) for 5 football seasons (2004-2005 through 2008-2009), including all preseason, regular season, and postseason practice and competition data. The incidence, epidemiology, and risk factors for turf toe injury, defined as injury to the connective tissue of the first MTP joint, plantar plate complex, and/or sesamoid fracture, were determined.The overall incidence of turf toe injuries in NCAA football players was 0.062 per 1000 athlete-exposures (A-Es; 95% CI 0.052, 0.072). Athletes were nearly 14 times more likely to sustain the injury during games compared to practice, with a mean days lost due to injury of 10.1 (7.9, 12.4). Fewer than 2% of turf toe injuries required operative intervention. There was a significantly higher injury rate on third-generation artificial surfaces compared to natural grass (0.087 per 1000 A-E [0.067, 0.11] vs 0.047 per 1000 A-E [0.036, 0.059]). The majority of injuries occurred as a result of contact with the playing surface (35.4%) or contact with another player (32.7%), and running backs and quarterbacks were the most common positions to suffer turf toe injury.Our data suggest a significantly higher incidence of turf toe injuries during games, a greater susceptibility among running backs and quarterbacks, and a significant contribution of playing surface to risk of injury. Though turf toe injuries may be less common that previously reported in elite football players, these injuries warrant appropriate acute and long-term management to prevent long-term dysfunction.Level IV, case series.

    View details for DOI 10.1177/1071100713514038

    View details for Web of Science ID 000339327300003

    View details for PubMedID 24334272

  • The Use of PRP in Ligament and Meniscal Healing. Sports medicine and arthroscopy review Braun, H. J., Wasterlain, A. S., Dragoo, J. L. 2013; 21 (4): 206-212


    Platelet-rich plasma (PRP) has become a popular treatment for acute and chronic soft tissue injuries. Although the majority of research has focused on its use in tendinopathy, PRP may have potential in meniscus and ligament healing. Some level II studies support a possible benefit for anterior cruciate ligament (ACL) allograft maturation, and preliminary animal studies point to a potential role for PRP in primary ACL repair. However, randomized controlled trials have not demonstrated a benefit of PRP for ACL tendon allograft-tunnel integration. To date, 2 studies document the use of PRP for meniscal applications, but this field is largely unexplored. With respect to ligament and meniscal applications, the current literature suggests PRP may be promising for primary ACL repair in skeletally immature patients, ACL graft maturation, and repair of meniscal tears in the avascular zone.

    View details for DOI 10.1097/JSA.0000000000000005

    View details for PubMedID 24212368

  • Six-week gait retraining program reduces knee adduction moment, reduces pain, and improves function for individuals with medial compartment knee osteoarthritis. Journal of orthopaedic research Shull, P. B., Silder, A., Shultz, R., Dragoo, J. L., Besier, T. F., Delp, S. L., Cutkosky, M. R. 2013; 31 (7): 1020-1025


    This study examined the influence of a 6-week gait retraining program on the knee adduction moment (KAM) and knee pain and function. Ten subjects with medial compartment knee osteoarthritis and self-reported knee pain participated in weekly gait retraining sessions over 6 weeks. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and a 10-point visual-analog pain scale score were measured at baseline, post-training (end of 6 weeks), and 1 month after training ended. Gait retraining reduced the first peak KAM by 20% (p?

    View details for DOI 10.1002/jor.22340

    View details for PubMedID 23494804

  • Epidemiology of syndesmosis injuries in intercollegiate football: incidence and risk factors from National Collegiate Athletic Association injury surveillance system data from 2004-2005 to 2008-2009. Clinical journal of sport medicine Hunt, K. J., George, E., Harris, A. H., Dragoo, J. L. 2013; 23 (4): 278-282


    OBJECTIVE:: To describe the incidence and risk factors for high ankle sprains (ie, syndesmosis injuries) among National Collegiate Athletic Association (NCAA) football players. DESIGN:: Descriptive epidemiologic study. SETTING:: Data were examined from the NCAA's Injury Surveillance System (ISS) for 5 football seasons (from 2004-2005 to 2008-2009). PARTICIPANTS:: All NCAA men's football programs participating in the ISS. ASSESSMENT OF RISK FACTORS:: No additional risk factors were introduced as a result of this analysis. MAIN OUTCOME MEASURES:: For partial and complete syndesmosis injuries, outcome measures included incidence, time lost from participation, and requirement for surgical repair. RESULTS:: The overall incidence of high ankle sprains in NCAA football players was 0.24 per 1000 athlete exposures, accounting for 24.6% of all ankle sprains. Athletes were nearly 14 times more likely to sustain the injury during games compared with practice; complete syndesmosis injuries resulted in significantly greater time lost compared with partial injuries (31.3 vs 15.8 days). Less than 3% of syndesmosis injuries required surgical intervention. There was a significantly higher injury incidence on artificial surfaces compared with natural grass. The majority of injuries (75.2%) occurred during contact with another player. CONCLUSIONS:: Our data suggest a significantly higher incidence of syndesmosis injuries during games, during running plays, and to running backs and interior defensive linemen. The wide range in time lost from participation for complete syndesmosis injuries underscores the need for improved understanding of injury mechanism and classification of injury severity such that prevention, safe return to play protocols, and outcomes can be further improved.

    View details for DOI 10.1097/JSM.0b013e31827ee829

    View details for PubMedID 23339895

  • Effect of airline travel on performance: a review of the literature. British journal of sports medicine Leatherwood, W. E., Dragoo, J. L. 2013; 47 (9): 561-567


    The need for athletes to travel long distances has spurred investigation into the effect of air travel across multiple time zones on athletic performance. Rapid eastward or westward travel may negatively affect the body in many ways; therefore, strategies should be employed to minimise these effects which may hamper athletic performance. In this review, the fundamentals of circadian rhythm disruption are examined along with additional effects of airline travel including jet lag, sleep deprivation, travel at altitude and nutritional considerations that negatively affect performance. Evidence-based recommendations are provided at the end of the manuscript to minimise the effects of airline travel on performance.

    View details for DOI 10.1136/bjsports-2012-091449

    View details for PubMedID 23143931

  • The effect of playing surface on the incidence of ACL injuries in National Collegiate Athletic Association American Football KNEE Dragoo, J. L., Braun, H. J., Harris, A. H. 2013; 20 (3): 191-195


    Artificial playing surfaces are widely used for American football practice and competition and anterior cruciate ligament (ACL) injuries are common. This study analyzed the National Collegiate Athletic Association (NCAA) Injury Surveillance System (ISS) men's football ACL injury database from 2004-2005 through 2008-2009 to determine the effect of playing surface on ACL injury in NCAA football athletes.This database was reviewed from the 2004-2005 through 2008-2009 seasons using the specific injury code, "Anterior cruciate ligament (ACL) complete tear." The injury rate was computed for competition and practice exposures. Ninety-five percent confidence intervals were calculated using assumptions of a Poisson distribution. Pair-wise, two-sample tests of equality of proportions with a continuity correction were used to estimate the associations of risk factors.There was an incidence rate of 1.73 ACL injuries per 10,000 athlete-exposures (A-Es) (95% CI 1.47-2.0) on artificial playing surfaces compared with a rate of 1.24 per 10,000 A-Es (1.05-1.45, p<0.001) on natural grass. The rate of ACL injury on artificial surfaces is 1.39 times higher than the injury rate on grass surfaces. Non-contact injuries occurred more frequently on artificial turf surfaces (44.29%) than on natural grass (36.12%).NCAA football players experience a greater number of ACL injuries when playing on artificial surfaces.

    View details for DOI 10.1016/j.knee.2012.07.006

    View details for Web of Science ID 000319533700010

    View details for PubMedID 22920310

  • The effect of local anaesthetics on synoviocytes: a possible indirect mechanism of chondrolysis. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA Braun, H. J., Busfield, B. T., Kim, H. J., Scuderi, G. J., Dragoo, J. L. 2013; 21 (6): 1468-1474


    While the effect of local anaesthetics on chondrocyte viability is widely documented, the effect of these medications on synoviocytes is largely unknown. The purpose of this study was to understand the effect of 0.5% bupivacaine and 0.5% bupivacaine with epinephrine on synoviocyte viability, cytokine and growth factor release, and breakdown product formation.Rabbit fibroblast-like synoviocyte (Type B) cultures were perfused with 0.5% bupivacaine or 0.5% bupivacaine with epinephrine (1:200,000) for 24h. Cell viability was evaluated using a two-colour fluorescence assay. The supernatant was analysed using multiplex inflammatory and matrix metalloproteinase assays.Synoviocytes treated for 24h with 0.5% bupivacaine with epinephrine demonstrated a significant decrease in viability (31.319.4% cell death) when compared with synoviocytes cultured in control media (3.81.3% cell death, p=0.000) and those cultured in 0.5% bupivacaine alone (12.611.1% cell death, p=0.003). No significant decrease in cell viability was observed in synoviocytes treated with 0.5% bupivacaine compared to those in control media (12.611.1% vs 3.81.3% cell death, p=0.194). Significantly greater amounts of MMP-1 (47.09.2pg/ml) and MMP-3 (250.068.8pg/ml) were observed in 0.5% bupivacaine cultures compared with controls (14.314.3, p=0.023 and 72.084.9, p=0.045, respectively).0.5% bupivacaine with epinephrine caused a significant increase in cell death of the synoviocytes, while 0.5% bupivacaine alone produced cell injury and a significant release of matrix metalloproteinases, which may also lead to indirect injury of the surrounding chondrocytes. These results may help explain the onset of chondrolysis observed in patients who have been treated with intra-articular local anaesthetics.

    View details for DOI 10.1007/s00167-012-2104-5

    View details for PubMedID 22717739

  • Application of advanced magnetic resonance imaging techniques in evaluation of the lower extremity. Radiologic clinics of North America Braun, H. J., Dragoo, J. L., Hargreaves, B. A., Levenston, M. E., Gold, G. E. 2013; 51 (3): 529-545


    This article reviews current magnetic resonance imaging (MR imaging) techniques for imaging the lower extremity, focusing on imaging of the knee, ankle, and hip joints. Recent advancements in MR imaging include imaging at 7 T, using multiple receiver channels, T2* imaging, and metal suppression techniques, allowing more detailed visualization of complex anatomy, evaluation of morphologic changes within articular cartilage, and imaging around orthopedic hardware.

    View details for DOI 10.1016/j.rcl.2012.12.001

    View details for PubMedID 23622097

  • Author's response. American journal of sports medicine Wasterlain, A. S., Dragoo, J. L. 2013; 41 (5): NP23-6

    View details for PubMedID 23767064

  • Application of advanced magnetic resonance imaging techniques in evaluation of the lower extremity. Radiologic clinics of North America Braun, H. J., Dragoo, J. L., Hargreaves, B. A., Levenston, M. E., Gold, G. E. 2013; 51 (3): 529-545

    View details for DOI 10.1016/j.rcl.2012.12.001

    View details for PubMedID 23622097

  • The effect of nonsteroidal anti-inflammatory drugs on tissue healing KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY Chen, M. R., Dragoo, J. L. 2013; 21 (3): 540-549


    Non-selective (NSAIDs) and selective (COX-2) nonsteroidal anti-inflammatory drugs are commonly used for their analgesic and anti-inflammatory effects. Their role after orthopaedic surgery has been infrequently described and remains controversial because of unclear effects on soft tissue and bone healing. This study critically reviews the available literature to describe the effects of NSAIDs and COX-2 inhibitors on soft tissue and bone healing.A Medline search was performed using NSAIDs or COX-2 inhibitors and tissue healing. The combined search yielded 637 articles. Following exclusion, 44 articles were deemed relevant with 9 articles on soft tissue healing and 35 articles on bone healing. The available evidence is based primarily on animal data (39 studies), with considerable variation in study methods.In regard to soft tissue healing, there is insufficient evidence of a detrimental effect when using either NSAIDs or COX-2 inhibitors at standard doses for?2weeks. For soft tissue to bone healing, a limited number of studies demonstrate impairment in healing. However, with respect to bone healing, indomethacin appears to have a clear detrimental effect, with less substantial evidence for other NSAIDs.Short-term, low-dose use of NSAIDs and COX-2 inhibitors does not appear to have a detrimental effect following soft tissue injury, but is inhibitory in cases involving bony healing. However, additional well-controlled human studies are necessary to draw more definitive conclusions regarding their role. Clinically, the prudent use of anti-inflammatory medications following sports medicine injuries and surgeries appears to be a reasonable option in clinical practice unless bone healing is required.III.

    View details for DOI 10.1007/s00167-012-2095-2

    View details for Web of Science ID 000315046200004

    View details for PubMedID 22744434

  • Toe-in gait reduces the first peak knee adduction moment in patients with medial compartment knee osteoarthritis. Journal of biomechanics Shull, P. B., Shultz, R., Silder, A., Dragoo, J. L., Besier, T. F., Cutkosky, M. R., Delp, S. L. 2013; 46 (1): 122-128


    The first peak of the knee adduction moment has been linked to the presence, severity, and progression of medial compartment knee osteoarthritis. The objective of this study was to evaluate toe-in gait (decreased foot progression angle from baseline through internal foot rotation) as a means to reduce the first peak of the knee adduction moment in subjects with medial compartment knee osteoarthritis. Additionally, we examined whether the first peak in the knee adduction moment would cause a concomitant increase in the peak external knee flexion moment, which can eliminate reductions in the medial compartment force that result from lowering the knee adduction moment. We tested the following hypotheses: (a) toe-in gait reduces the first peak of the knee adduction moment, and (b) toe-in gait does not increase the peak external knee flexion moment. Twelve patients with medial compartment knee osteoarthritis first performed baseline walking trials and then toe-in gait trials at their self-selected speed on an instrumented treadmill in a motion capture laboratory. Subjects altered their foot progression angle from baseline to toe-in gait by an average of 5 (p<0.01), which reduced the first peak of the knee adduction moment by an average of 13% (p<0.01). Toe-in gait did not increase the peak external knee flexion moment (p=0.85). The reduced knee adduction moment was accompanied by a medially-shifted knee joint center and a laterally-shifted center of pressure during early stance. These results suggest that toe-in gait may be a promising non-surgical treatment for patients with medial compartment knee osteoarthritis.

    View details for DOI 10.1016/j.jbiomech.2012.10.019

    View details for PubMedID 23146322

  • Toe-in gait reduces the first peak knee adduction moment in patients with medial compartment knee osteoarthritis JOURNAL OF BIOMECHANICS Shull, P. B., Shultz, R., Slider, A., Dragoo, J. L., Besier, T. F., Cutkosky, M. R., Delp, S. L. 2013; 46 (1): 122-128
  • The Systemic Effects of Platelet-Rich Plasma Injection AMERICAN JOURNAL OF SPORTS MEDICINE Wasterlain, A. S., Braun, H. J., Harris, A. H., Kim, H., Dragoo, J. L. 2013; 41 (1): 186-193


    Platelet-rich plasma (PRP) is an autologous blood product used to treat acute and chronic tendon, ligament, and muscle injuries in over 86,000 athletes in the United States annually. The World Anti-Doping Agency (WADA) banned intramuscular PRP injections in competitive athletes in 2010 because of concerns that it may increase performance-enhancing growth factors. The ban on PRP was removed in 2011 because of limited evidence for a systemic ergogenic effect of PRP, but the growth factors within PRP remain prohibited.To quantify the effect of PRP injection on systemic growth factors with performance-enhancing effects and to identify molecular markers to detect treated athletes.Descriptive laboratory study.Six ergogenic growth factors monitored by WADA-human growth hormone (hGH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), basic fibroblast growth factor (bFGF or FGF-2), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-BB (PDGF-BB)-were measured in 25 patients before (baseline) and at 0.25, 3, 24, 48, 72, and 96 hours after intratendinous leukocyte-rich PRP injection. Eating and exercise were prohibited for 3 hours before testing. Growth factors were quantified by enzyme-linked immunosorbent assay, and the change relative to each patient's baseline was calculated.Relative to serum, PRP contained significantly more bFGF (226 vs 5 pg/mL), VEGF (1426 vs 236 pg/mL), and PDGF-BB (26,285 vs 392 pg/mL), but IGF-1 and hGH were not elevated. Serum levels increased significantly for IGF-1 at 24 and 48 hours, for bFGF at 72 and 96 hours, and for VEGF at 3, 24, 48, 72, and 96 hours after PRP injection. Additionally, VEGF was increased in all 25 patients after PRP treatment.Serum IGF-1, VEGF, and bFGF levels are significantly elevated after PRP injection, supporting a possible ergogenic effect of PRP. An indirect marker for hGH doping, the product of IGFBP-3 IGF-1, also significantly increased after PRP. Platelet-rich plasma appears to trigger an increase in circulating growth factors through activating biological pathways rather than by serving as a vehicle for the direct delivery of presynthesized growth factors. Elevated VEGF was observed in all patients after PRP, and ?88% of patients had elevated VEGF at each time point from 3 to 96 hours after PRP, suggesting that VEGF may be a sensitive molecular marker to detect athletes recently treated with PRP.This is the first and only adequately powered study of the systemic effects of PRP. We present evidence that PRP contains and may trigger systemic increases in substances currently banned in competitive athletes. Finally, we provide evidence that VEGF could serve as a useful molecular marker to detect athletes treated with PRP.

    View details for DOI 10.1177/0363546512466383

    View details for Web of Science ID 000313008300026

    View details for PubMedID 23211708

  • Postarthroscopic Infection in the Knee following Medical or Dental Procedures. Case reports in orthopedics Swank, K., Dragoo, J. L. 2013; 2013: 974017-?


    Knee infection is a relatively rare complication after arthroscopic knee surgery (Babcok et al., 2002), with reported incidences ranging from 0.1% to 3.4% (Babcok et al., 2002 and Bert et al., 2007). Although postoperative dental and surgical procedures were formerly considered a risk factor for infection in arthroplasty patients, the American Dental Association (ADA) and Academy of Orthopaedic Surgery (AAOS) no longer recommend prophylactic antibiotics for patients with prosthetic joints and do not make recommendations concerning patients who have recently undergone arthroscopic surgery (J. M. Bert and T. M. Bert, 2010). We report two patients who had an uncomplicated postoperative course until having a procedure and then developed a septic knee.

    View details for DOI 10.1155/2013/974017

    View details for PubMedID 24191214

  • Optimizing lavage during knee arthroscopy: A three-dimensional MRI study JOURNAL OF MAGNETIC RESONANCE IMAGING Nord, R. M., Badowski, N., Elkins, C., Alley, M., Harris, A. H., Dragoo, J. L. 2013; 37 (1): 201-207


    To determine the best positioning and the resulting fluid flow patterns inside the knee during arthroscopy, reducing the surgical morbidity associated with the arthroscopic irrigation and debridement of a septic knee joint.Three-dimensional MRI, using an MRI-compatible human cadaveric knee arthroscopic model, generated fluid flow diagrams and velocity vector data. This was analyzed for six different arthroscopic configurations and at six different locations within the knee joint.At any one static arthroscopic position, fluid flow velocity differed at the various locations in the knee, often with statistically significantly greater flow at one location over another. In general, flow was greatest at the location at which the inflow cannula terminated and preferentially flowed directly to the outflow cannula location, neglecting spaces in the knee that were not on this direct path. Three-portal arthroscopy provided no benefit over two-portal arthroscopy.To maximize arthroscopic lavage throughout all compartments in the knee, the arthroscopist must individually enter each space in the knee. Static arthroscopy in the setting of knee sepsis may lead to inadequate flow in certain areas of the knee and may lead to treatment failure. Three-portal arthroscopy does not improve lavage efficiency.

    View details for DOI 10.1002/jmri.23787

    View details for Web of Science ID 000312720000022

    View details for PubMedID 22941502

  • Acromioclavicular Joint Injuries in National Collegiate Athletic Association Football Data From the 2004-2005 Through 2008-2009 National Collegiate Athletic Association Injury Surveillance System AMERICAN JOURNAL OF SPORTS MEDICINE Dragoo, J. L., Braun, H. J., Bartlinski, S. E., Harris, A. H. 2012; 40 (9): 2066-2071


    Injuries to the shoulder are common in collegiate football, and injuries to the acromioclavicular (AC) joint have previously accounted for up to 41% of all shoulder injuries.To determine the incidence and epidemiology of injury to the AC joint in National Collegiate Athletic Association (NCAA) football athletes.Descriptive epidemiology study.The NCAA Injury Surveillance System (ISS) men's football database was reviewed from the 2004-2009 playing seasons. The exposure data set from the same years was reviewed for the purposes of computing rates of injury per athlete exposure (AE). The injury rate (number of injuries divided by number of AEs) was computed per 10,000 AEs for competition and practice exposures. Ninety-five percent confidence intervals (95% CIs) for the incidence rates were calculated using assumptions of a Poisson distribution.According to the estimates made by the NCAA ISS, a total of 748 injuries to the AC joint occurred in NCAA football players during 2,222,155 AEs, accounting for 4.49% of all injuries sustained during this 5-year surveillance period. The overall rate of injury was 3.34 per 10,000 AEs (95% CI, 3.10-3.59). Players were 11.68 (95% CI, 10.11-13.49) times more likely to sustain an injury in games than practices. Partial sprains (types I or II) accounted for 96.4% of injuries, while complete sprains (?type III) accounted for the remaining 3.6%. The average amount of time lost per injury was 11.61 days. Complete sprains resulted in a mean time loss of 31.9 days (95% CI, 24.4-39.6) while partial injuries resulted in 11.0 days lost (95% CI, 9.6-12.3). Overall, 2.41% of injuries underwent surgical intervention, with 22.2% of complete sprains and 1.7% of partial injuries resulting in surgery. Complete sprains of the AC joint were 13.5 (95% CI, 4.63-35.26) times more likely to result in surgical intervention than partial sprains. The majority of injuries (71.93%) resulted from contact with another player and 47.09% occurred while tackling or being tackled. Of all injuries, 47.63% occurred during offensive plays, while defense accounted for 20.77%.AC joint injuries in NCAA football players are predominantly low-grade sprains, leading to approximately 12 days of lost competition. The few severe sprains that occurred often resulted in surgery or required approximately 5 weeks of rehabilitation.

    View details for DOI 10.1177/0363546512454653

    View details for Web of Science ID 000308230600023

    View details for PubMedID 22869625

  • The chondrotoxicity of single-dose corticosteroids KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY Dragoo, J. L., Danial, C. M., Braun, H. J., Pouliot, M. A., Kim, H. J. 2012; 20 (9): 1809-1814


    Corticosteroids are commonly injected into the joint space. However, studies have not examined the chondrotoxicity of one-time injection doses. The purpose of this study is to evaluate the effect of dexamethasone sodium phosphate (Decadron), methylprednisolone acetate (Depo-Medrol), betamethasone sodium phosphate and betamethasone acetate (Celestone Soluspan), and triamcinolone acetonide (Kenalog) on human chondrocyte viability in vitro.Single-injection doses of each of the corticosteroids were separately delivered to human chondrocytes for their respective average duration of action and compared to controls using a bioreactor containing a continuous infusion pump constructed to mimic joint fluid metabolism. A 14-day time-controlled trial was also performed. A live/dead reduced biohazard viability/cytotoxicity assay was used to quantify chondrocyte viability.Over their average duration of action, betamethasone sodium phosphate/acetate solution and triamcinolone acetonide caused significant decreases in chondrocyte viability compared to control media (19.8 2.9% vs. 5.2 2.1%, P = 0.0025 and 10.2 1.3% vs. 4.8 0.9%, P = 0.0049, respectively). In the 14-day trial, only betamethasone sodium phosphate/acetate solution caused a significant decrease in chondrocyte viability compared to control media (21.5% vs. 4.6%, P < 0.001).A single-injection dose of betamethasone sodium phosphate and betamethasone acetate solution illustrated consistent and significant chondrotoxicity using a physiologically relevant in vitro model and should be used with caution. Given the observed chondrotoxicity of triamcinolone acetonide in a single trial, there may be some evidence that this medication is chondrotoxic. However, at 14 days, betamethasone sodium phosphate and betamethasone acetate was the only condition that caused significant cell death.

    View details for DOI 10.1007/s00167-011-1820-6

    View details for Web of Science ID 000307816500022

    View details for PubMedID 22186921

  • The effect of local anesthetic and corticosteroid combinations on chondrocyte viability KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY Braun, H. J., Wilcox-Fogel, N., Kim, H. J., Pouliot, M. A., Harris, A. H., Dragoo, J. L. 2012; 20 (9): 1689-1695


    Local anesthetic and corticosteroid combination injections are often used in clinical practice, however research investigating the chondrotoxic properties of these combinations is minimal. The goal of this study was to evaluate the effect of single injection doses of 1% lidocaine or 0.25% bupivacaine in combination with single injection doses of dexamethasone sodium phosphate (Decadron), methylprednisolone acetate (Depo-Medrol), betamethasone sodium phosphate and betamethasone acetate (Celestone Soluspan), or triamcinolone acetonide (Kenalog) on human chondrocyte viability.All treatment conditions were delivered to human chondrocytes in vitro for the medication's respective average duration of action using a bioreactor containing a continuous infusion pump constructed to mimic joint fluid metabolism. A two-color fluorescence assay was used to evaluate cell viability. A mixed-effects regression model was used to evaluate the mean differences in cell viability between treatment groups.At 14 days, a single injection dose of 1% lidocaine or 0.25% bupivacaine in combination with betamethasone sodium phosphate and betamethasone acetate solution illustrated significant chondrotoxicity when compared with the local anesthetics alone (P < 0.01). Methylprednisolone acetate and Triamcinolone acetonide both showed significant evidence of chondrotoxicity (P = 0.013; P = 0.016, respectively) when used in combination with 1% lidocaine compared with lidocaine alone, but showed no significant chondrotoxicity in combination with 0.25% bupivacaine (P's = n.s.).Clinicians should use caution when injecting 1% lidocaine or 0.25% bupivacaine in conjunction with betamethasone sodium phosphate and betamethasone acetate solution due to its pronounced chondrotoxic effect in this study. 1% lidocaine used in combination with methylprednisolone acetate or triamcinolone acetonide also led to significant chondrotoxicity.

    View details for DOI 10.1007/s00167-011-1728-1

    View details for Web of Science ID 000307816500006

    View details for PubMedID 22037813

  • Evaluation of a one-stage ACL revision Technique using bone void filler after cyclic loading KNEE Tse, B. K., Vaughn, Z. D., Lindsey, D. P., Dragoo, J. L. 2012; 19 (4): 477-481


    Revision anterior cruciate ligament (ACL) reconstruction often requires a two-stage approach. This study analyzes the biomechanical properties after cyclic loading of a one-stage ACL revision technique using a calcium phosphate bone cement.Arthroscopic reconstruction of the ACL was performed in 5 matched pairs of fresh-frozen cadaveric knees separated into two groups. The control group underwent a standard reconstruction with a bone-patellar tendon-bone autograft with bioabsorbable interference screw fixation. The experimental group simulated a failed reconstruction by drilling a 12 mm hole and underwent a revision after filling it with a bioabsorbable calcium phosphate bone cement. The specimens were dissected, scanned for bone mineral density, and cyclically loaded on a mechanical testing system (preload of 250 cycles of 5-75 N at 0.5 Hz followed by 10,000 cycles of 20-150 N at 1 Hz). Intact specifmens underwent a load-to-failure protocol of 50mm/min. Ultimate load, stiffness, and modes of failure were recorded. Data was analyzed using paired t-tests.All specimens completed the mechanical testing protocol. The control group had a mean maximum load of 471.33 N (SD 220.73 N) and the experimental group had 453.54 N (SD 152.36; p=0.84). There were no statistically significant differences in maximum load or stiffness. No correlation between bone mineral density (BMD) and maximum load was found.Using calcium phosphate filler in a single-stage ACL revision is biomechanically viable. Further testing of long-term incorporation of the ACL graft in an animal model, along with human clinical trials, should be performed before there is clinical acceptance of this technique.

    View details for DOI 10.1016/j.knee.2011.06.013

    View details for Web of Science ID 000305852300046

    View details for PubMedID 21775147

  • Comparison of the acute inflammatory response of two commercial platelet-rich plasma systems in healthy rabbit tendons. American journal of sports medicine Dragoo, J. L., Braun, H. J., Durham, J. L., Ridley, B. A., Odegaard, J. I., Luong, R., Arnoczky, S. P. 2012; 40 (6): 1274-1281


    Numerous studies have shown platelet-rich plasma (PRP) preparations differ with respect to the inclusion of certain blood components, which may affect the host's cellular response.This study evaluated the inflammatory effect of Biomet GPS III leukocyte-rich PRP (LR-PRP) versus MTF Cascade leukocyte-poor PRP (LP-PRP) after intratendinous injection in an animal model. The authors anticipated that LR-PRP would incite a greater acute inflammatory response than LP-PRP.Controlled laboratory study.A total of 17 skeletally mature New Zealand White rabbits were tested. In all cases, healthy patellar tendons were treated. In the control animals, one patellar tendon was injected with 2 mL autologous whole blood, and the other was injected with 2 mL sterile saline. Seven total tendons were injected with whole blood, and 7 tendons were injected with saline. In the experimental animals, one patellar tendon was injected with 2 mL LR-PRP, and the other was injected with 2 mL LP-PRP. Ten tendons were injected with LR-PRP, and 10 tendons were injected with LP-PRP. Animals were euthanized at 5 or 14 days after injection. Tendons were harvested and stained using hematoxylin and eosin and scored semi-quantitatively for total white blood cells (WBCs), mononuclear cells (macrophages and lymphocytes), polymorphonuclear cells (PMNs), vascularity, fiber structure, and fibrosis.At 5 days after injection, tendons treated with LR-PRP had significantly greater overall tendon scores (6.3 1.79 vs 1.8 1.64, P = .012), as well as mean scores for fiber structure (1.4 0.22 vs 0.50 0.50, P = .012), denoting disrupted composition, total WBCs (1.1 0.89 vs 0.10 0.22, P = .014), mononuclear cells (macrophages and lymphocytes) (0.80 0.45 vs 0.10 0.22, P = .014), vascularity (1.7 0.27 vs 0.80 0.16, P = .008), and fibrosis (1.0 0.35 vs 0.3 0.45, P = .037) compared with tendons treated with LP-PRP. Otherwise, there were no significant differences in mononuclear cells (P = .590), PMN cells (P = 1.00), total WBCs (P = .811), vascularity (P = .650), or total tendon score (P = .596) in any of the treatment groups at 14 days.Compared with leukocyte-poor Cascade PRP, leukocyte-rich GPS III PRP causes a significantly greater acute inflammatory response at 5 days after injection. There is no significant difference in the inflammatory response or cellularity regardless of the injection type at 14 days after intratendinous injection.Platelet-rich plasma injections are frequently prepared using commercial systems and are administered for clinical treatment of chronic tendinopathy. It is important to characterize the cellular responses elucidated by different injection preparations to further understand their effect on tissue healing and aid clinical decision making. Future investigations are necessary to apply these findings to the clinical setting.

    View details for DOI 10.1177/0363546512442334

    View details for PubMedID 22495144

  • Comparison of the Acute Inflammatory Response of Two Commercial Platelet-Rich Plasma Systems in Healthy Rabbit Tendons AMERICAN JOURNAL OF SPORTS MEDICINE Dragoo, J. L., Braun, H. J., Durham, J. L., Ridley, B. A., Odegaard, J. I., Richard Luong, R., Arnoczky, S. P. 2012; 40 (6): 1274-1281
  • Incidence and Risk Factors for Injuries to the Anterior Cruciate Ligament in National Collegiate Athletic Association Football Data From the 2004-2005 Through 2008-2009 National Collegiate Athletic Association Injury Surveillance System AMERICAN JOURNAL OF SPORTS MEDICINE Dragoo, J. L., Braun, H. J., Durham, J. L., Chen, M. R., Harris, A. H. 2012; 40 (5): 990-995


    Injuries to the anterior cruciate ligament (ACL) are common in athletic populations, particularly in athletes participating in football, soccer, and skiing.The purpose of this study was to analyze the National Collegiate Athletic Association (NCAA) Injury Surveillance System (ISS) men's football ACL injury database from the playing seasons of 2004-2005 through 2008-2009 to determine the incidence and epidemiology of complete injury to the ACL in NCAA football athletes.Descriptive epidemiology study.The NCAA ISS men's football database was reviewed from the 2004-2005 through 2008-2009 seasons using the specific injury code, "Anterior cruciate ligament (ACL) complete tear." The injury rate was computed for competition and practice exposures. Ninety-five percent confidence intervals (CIs) for the incident rates were calculated using assumptions of a Poisson distribution. Pairwise, 2-sample tests of equality of proportions with a continuity correction were used to estimate the associations of risk factors such as event type, playing surface, season segment, and football subdivision. Descriptive data were also described.The ACL injury rate during games (8.06 per 10,000 athlete-exposures [AEs] 95% CI, 6.80-9.42) was significantly greater than the rate during practice (0.8 per 10,000 AEs 95% CI, 0.68-0.93). Players were 10.09 (95% CI, 8.08-12.59) times more likely to sustain an ACL injury in competition when compared with practices. When practice exposures were analyzed separately, the injury rate was significantly greater during scrimmages (3.99 per 10,000 AEs 95% CI, 2.29-5.94) compared with regular practices (0.83 per 10,000 AEs 95% CI, 0.69-0.97) and walk-throughs (0 per 10,000 AEs 95% CI, 0-0.14). There was an incidence rate of 1.73 ACL injuries per 10,000 AEs (95% CI, 1.47-2.0) on artificial playing surfaces compared with a rate of 1.24 per 10,000 AEs (95% CI, 1.05-1.45) on natural grass. The rate of ACL injury on artificial surfaces is 1.39 (95% CI, 1.11-1.73) times higher than the injury rate on grass surfaces.Between 2004 and 2009, NCAA football players experienced a greater number of ACL injuries in games compared with practices, in scrimmages compared with regular practices, and when playing on artificial turf surfaces. This latter finding will need to be confirmed by additional studies.

    View details for DOI 10.1177/0363546512442336

    View details for Web of Science ID 000303323900006

    View details for PubMedID 22491794

  • Effects of Arm Position on Maximizing Intra-Articular Visualization of the Biceps Tendon: A Cadaveric Study ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY Hart, N. D., Golish, S. R., Dragoo, J. L. 2012; 28 (4): 481-485


    The purpose of this study was to assess the intra-articular length of the biceps tendon in various shoulder and arm positions and identify the position in which the extra-articular portion of the tendon is maximally visualized within the glenohumeral joint.We measured 18 positions in 4 fresh-frozen cadaveric shoulders for a total of 72 measurements. In each measurement the position of the proximal biceps tendon was measured relative to a baseline measurement in neutral position (0 shoulder flexion, 0 shoulder abduction, 0 elbow flexion, 0 shoulder rotation). Positions measured ranged between the following: 0 and 30 shoulder flexion; 0 and 40 shoulder abduction; 0 and 90 elbow flexion; and 0 neutral, 30 internal, and 30 external shoulder rotation.The position creating the greatest increase in intra-articular biceps tendon length from baseline was 30 shoulder flexion, 40 shoulder abduction, 90 elbow flexion, and 0 rotation. On average, 56% of the tendon within the bicipital groove is brought into view by the maximal position relative to baseline. In maximizing intra-articular biceps tendon length, the effect of elbow flexion was highly significant (P < .001) and the combined effect of shoulder flexion-abduction was significant (P = .016).The position of 30 shoulder flexion, 40 shoulder abduction, and 90 elbow flexion significantly increases the excursion of the proximal biceps tendon relative to a neutral position. Over 50% of the tendon within the bicipital groove at baseline can be pulled out of the groove by placing the extremity in the maximal position and using an arthroscopic probe. Rotation of the humerus does not improve intra-articular excursion.Maximizing the intra-articular tendon length by arm positional change is likely to be useful for arthroscopic examination of the biceps tendon.

    View details for DOI 10.1016/j.arthro.2011.08.313

    View details for Web of Science ID 000302131300007

    View details for PubMedID 22265042

  • The In Vitro Chondrotoxicity of Single-Dose Local Anesthetics 37th Annual Meeting of the American-Orthopaedic-Society-for-Sports-Medicine (AOSSM) Dragoo, J. L., Braun, H. J., Kim, H. J., Phan, H. D., Golish, S. R. SAGE PUBLICATIONS INC. 2012: 794?99


    The administration of amide-type local anesthetics to cartilaginous tissues has revealed potential chondrotoxicity.This study evaluated whether administration of single doses of 1% lidocaine, 0.25% bupivacaine, and 0.5% ropivacaine resulted in decreased chondrocyte viability or cartilage matrix degradation in vitro.Controlled laboratory study.Monolayer human chondrocytes and intact cartilage samples were cultured for 1 week in media. Each drug was delivered in a custom bioreactor over its clinical duration of action. A Live/Dead Viability/Cytotoxicity Assay was used to determine the ratio of dead to live cells for monolayer chondrocyte cultures compared with controls. Damage to the cartilage extracellular matrix (ECM) in en bloc cartilage samples was evaluated by analysis of DNA, glycosaminoglycan (GAG), and collagen content.Chondrocytes treated for 3 hours with a single dose of 1% lidocaine exhibited significantly more cell death (7.9%) compared with control media (2.9%; P < .001). No significant difference in cell death was observed in chondrocytes treated for 6 hours with 0.25% bupivacaine (2.7%) versus controls (2.8%; P = .856) or cells treated for 12 hours in 0.5% ropivacaine (2.9%) versus controls (2.4%; P = .084). There was no significant difference in GAG expression (P = .627) or DNA-normalized GAG expression (P = .065) between the intact cartilage treatment groups; however, the DNA-normalized GAG expression was markedly lower in cartilage cultures treated with 1% lidocaine (3.36 1.15) compared with those in control media (7.61 3.83).The results of this in vitro study indicate that a single-dose administration of 1% lidocaine resulted in a significant decrease in chondrocyte viability when compared with control cultures.Single-dose injections of 1% lidocaine may be significantly chondrotoxic, and further investigation regarding in vivo chondrotoxicity appears warranted.

    View details for DOI 10.1177/0363546511434571

    View details for Web of Science ID 000302285100008

    View details for PubMedID 22287644

  • Evaluation and Treatment of Disorders of the Infrapatellar Fat Pad SPORTS MEDICINE Dragoo, J. L., Johnson, C., Mcconnell, J. 2012; 42 (1): 51-67


    The infrapatellar fat pad (IFP), also known as Hoffa's fat pad, is an intracapsular, extrasynovial structure that fills the anterior knee compartment, and is richly vascularized and innervated. Its degree of innervation, the proportion of substance-P-containing fibres and close relationship to its posterior synovial lining implicates IFP pathologies as a source of infrapatellar knee pain. Though the precise function of the IFP is unknown, studies have shown that it may play a role in the biomechanics of the knee or act as a store for reparative cells after injury. Inflammation and fibrosis within the IFP, caused by trauma and/or surgery can lead to a variety of arthrofibrotic lesions including Hoffa's disease, anterior interval scarring and infrapatellar contracture syndrome. Lesions or mass-like abnormalities rarely occur within the IFP, but their classification can be narrowed down by radiographical appearance. Clinically, patients with IFP pathology present with burning or aching infrapatellar anterior knee pain that can often be reproduced on physical exam with manoeuvres designed to produce impingement. Sagittal MRI is the most common imaging technique used to assess IFP pathology including fibrosis, inflammation, oedema, and mass-like lesions. IFP pathology is often successfully managed with physical therapy. Passive taping is used to unload or shorten an inflamed IFP, and closed chain quadriceps exercises can improve lower limb control and patellar congruence. Training of the gluteus medius and stretching the anterior hip may help to decrease internal rotation of the hip and valgus force at the knee. Gait training and avoiding hyperextension can also be used for long-term management. Injections within the IFP of local anaesthetic plus corticosteroids and IFP ablation with ultrasound guided alcohol injections have been successfully explored as treatments for IFP pain. IFP pathology refractory to physical therapy can be approached through a variety of operative treatments. Arthroscopic partial resection for IFP impingement and Hoffa's disease has showed favourable results; however, total excision of the IFP performed concomitantly with total knee arthroplasty (TKA) resulted in worse results when compared with TKA alone. Arthroscopic debridement of IFP fibrosis has been successfully used to treat extension block following anterior cruciate ligament reconstruction, and arthroscopic anterior interval release has been an effective treatment for pain associated with anterior interval scarring. Arthroscopic resection of infrapatellar plicae and denervation of the inferior pole of the patella have also been shown to be effective treatments for refractory infrapatellar pain.

    View details for Web of Science ID 000298974600004

    View details for PubMedID 22149697

  • In vitro chondrogenic differentiation of human adipose-derived stem cells with silk scaffolds. Journal of tissue engineering Kim, H. J., Park, S., Durham, J., Gimble, J. M., Kaplan, D. L., Dragoo, J. L. 2012; 3 (1): 2041731412466405-?


    Human adipose-derived stem cells have shown chondrogenic differentiation potential in cartilage tissue engineering in combination with natural and synthetic biomaterials. In the present study, we hypothesized that porous aqueous-derived silk protein scaffolds would be suitable for chondrogenic differentiation of human adipose-derived stem cells. Human adipose-derived stem cells were cultured up to 6 weeks, and cell proliferation and chondrogenic differentiation were investigated and compared with those in conventional micromass culture. Cell proliferation, glycosaminoglycan, and collagen levels in aqueous-derived silk scaffolds were significantly higher than in micromass culture. Transcript levels of SOX9 and type II collagen were also upregulated in the cell-silk constructs at 6 weeks. Histological examination revealed that the pores of the silk scaffolds were filled with cells uniformly distributed. In addition, chondrocyte-specific lacunae formation was evident and distributed in the both groups. The results suggest the biodegradable and biocompatible three-dimensional aqueous-derived silk scaffolds provided an improved environment for chondrogenic differentiation compared to micromass culture.

    View details for DOI 10.1177/2041731412466405

    View details for PubMedID 23316274

    View details for PubMedCentralID PMC3540700

  • Arthroscopic Releases for Arthrofibrosis of the Knee JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS Chen, M. R., Dragoo, J. L. 2011; 19 (11): 709-716


    Intra-articular inflammation or fibrosis may lead to decreased soft-tissue and capsular compliance, which may result in pain or loss of motion within the knee. Etiology of intra-articular fibrosis may include isolated anterior interval scarring and posterior capsular contracture, as well as fibrosis that involves the suprapatellar pouch or arthrofibrosis that involves the entire synovial space. Initial nonsurgical management, including compression, elevation, and physical therapy, can decrease knee pain and inflammation and maintain range of motion. Surgical management is indicated in the patient who fails conservative treatment. Surgical options include arthroscopic releases of the anterior interval, posterior capsule, and peripatellar and suprapatellar regions. Recent advances in arthroscopic technique have led to improved outcomes in patients with intra-articular fibrosis of the knee.

    View details for Web of Science ID 000296399800007

    View details for PubMedID 22052647

  • Prospective Correlation Between Serum Relaxin Concentration and Anterior Cruciate Ligament Tears Among Elite Collegiate Female Athletes AMERICAN JOURNAL OF SPORTS MEDICINE Dragoo, J. L., Castillo, T. N., Braun, H. J., Ridley, B. A., Kennedy, A. C., Golish, S. R. 2011; 39 (10): 2175-2180


    The female anterior cruciate ligament may be more susceptible to injury than the male anterior cruciate ligament because of the gender-specific expression of receptors for relaxin, a collagenolytic hormone that promotes remodeling of the anterior cruciate ligament.This study was undertaken to investigate whether collegiate female athletes with elevated serum relaxin concentrations (SRC) sustain anterior cruciate ligament tears at an increased rate compared with those with lower SRC.Cohort study (prognosis); Level of evidence, 2.From 2005 to 2010, 143 Division I female athletes from 2 universities participating in sports at high risk for anterior cruciate ligament tears (basketball, lacrosse, field hockey, soccer, gymnastics, and volleyball) were recruited to participate. Questionnaires and urine luteinizing hormone (LH) tests were used to determine participants' anterior cruciate ligament injury and menstrual history and to identify their mid-luteal phase or projected cycle days 21 to 24. Serum samples were obtained for progesterone and relaxin ELISA (enzyme-linked immunosorbent assay) analysis. Participants were monitored for anterior cruciate ligament injury over their 4-year National Collegiate Athletic Association athletic career.A total of 128 participants completed the study and were eligible for data analysis. The cumulative incidence of complete anterior cruciate ligament tear over the 4-year study period was 21.9%, and varied significantly by sport (P < .001). The mean SRC for athletes with anterior cruciate ligament tears (6.0 8.1 pg/mL) was significantly higher than that for those without anterior cruciate ligament tears (1.8 3.4 pg/mL; P = .013). In subgroup analysis of the 46 athletes who had detectable SRC, the cumulative incidence of anterior cruciate ligament tear was 14 of 46 (30.4%); the mean SRC among athletes with anterior cruciate ligament tears (14 of 46) was 12.1 7.7 pg/mL and without anterior cruciate ligament tears (32 of 46), 5.7 3.6 pg/mL (P = .002). When 6.0 pg/mL was set as the SRC cutoff for screening athletes for risk of anterior cruciate ligament tear in the subgroup with detectable relaxin levels, the test had 71% sensitivity, 69% specificity, 52% positive predictive value, 88% negative predictive value, and a relative risk of 4.4. These values were significant by ?(2) test (P = .003) and receiver operating characteristic analysis (P = .002).Elite female athletes with anterior cruciate ligament tears have higher SRC than those without tears. Those with an SRC greater than 6.0 pg/mL had over 4 times increased risk for a tear.Females with higher serum relaxin levels may be at increased risk for anterior cruciate ligament tears. Further investigation of the clinical utility of SRC testing is warranted.

    View details for DOI 10.1177/0363546511413378

    View details for Web of Science ID 000296287800023

    View details for PubMedID 21737831

  • Biomechanical analysis of bicortical versus unicortical locked plating of mid-clavicular fractures ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY Hamman, D., Lindsey, D., Dragoo, J. 2011; 131 (6): 773-778


    Operative fixation of displaced mid-shaft clavicle fractures has been shown to improve the functional outcomes and decrease the likelihood of non-union; however, little is known about the need for locking screws versus traditional screws. We, therefore, evaluated the strength of unicortical locked plating versus traditional bicortical non-locking fixation methods.Ten matched pairs of fresh, frozen cadaver clavicle specimens were obliquely osteotomized through the mid-shaft to represent the most common fracture pattern. After randomization, the clavicles were repaired using pre-contoured plates with either standard bicortical non-locking screws or unicortical locking screws. The constructs were then potted in cement and tested on a MTS machine using a custom gimble and evaluated for load to failure and axial and rotational stiffness.There was no significant difference between the constructs in terms of axial stiffness (locking 688.3 306.2 N/mm, non-locking 674.5 613.0 N/mm; p = 0.77) or load to failure (locking 720.1 232.0 N, non-locking 664.8 167.5 N; p = 0.46). However, rotational stiffness varied significantly (locking 1.70 0.91 N-m/mm, non-locking 2.49 0.78 N-m/mm, p = 0.049) with bicortical non-locking constructs exhibiting higher torque values.Unicortical fixation using pre-contoured plates and locking screws has a similar biomechanical profile compared to gold standard non-locked bicortical screws in cyclic axial compression and axial load to failure. Non-locking constructs were stiffer under rotational testing. This technique may provide a suitable biomechanical environment for bony healing. This may also improve the safety of clavicle plating by protecting infraclavicular structures from injury during drilling or screw penetration as it obviates the need for bicortical fixation.

    View details for DOI 10.1007/s00402-010-1212-2

    View details for Web of Science ID 000290669900008

    View details for PubMedID 21069362

  • Comparison of Growth Factor and Platelet Concentration From Commercial Platelet-Rich Plasma Separation Systems AMERICAN JOURNAL OF SPORTS MEDICINE Castillo, T. N., Pouliot, M. A., Kim, H. J., Dragoo, J. L. 2011; 39 (2): 266-271


    Clinical studies claim that platelet-rich plasma (PRP) shortens recovery times because of its high concentration of growth factors that may enhance the tissue repair process. Most of these studies obtained PRP using different separation systems, and few analyzed the content of the PRP used as treatment.This study characterized the composition of single-donor PRP produced by 3 commercially available PRP separation systems.Controlled laboratory study.Five healthy humans donated 100 mL of blood, which was processed to produce PRP using 3 PRP concentration systems (MTF Cascade, Arteriocyte Magellan, Biomet GPS III). Platelet, white blood cell (WBC), red blood cell, and fibrinogen concentrations were analyzed by automated systems in a clinical laboratory, whereas ELISA determined the concentrations of platelet-derived growth factor ?? and ?? (PDGF-??, PDGF-??), transforming growth factor ?1 (TGF-?1), and vascular endothelial growth factor (VEGF).There was no significant difference in mean PRP platelet, red blood cell, active TGF-?1, or fibrinogen concentrations among PRP separation systems. There was a significant difference in platelet capture efficiency. The highest platelet capture efficiency was obtained with Cascade, which was comparable with Magellan but significantly higher than GPS III. There was a significant difference among all systems in the concentrations of WBC, PDGF-??, PDGF-??, and VEGF. The Cascade system concentrated leukocyte-poor PRP, compared with leukocyte-rich PRP from the GPS III and Magellan systems.The GPS III and Magellan concentrate leukocyte-rich PRP, which results in increased concentrations of WBCs, PDGF-??, PDGF-??, and VEGF as compared with the leukocyte-poor PRP from Cascade. Overall, there was no significant difference among systems in the platelet concentration, red blood cell, active TGF-?1, or fibrinogen levels.Products from commercially available PRP separation systems produce differing concentrations of growth factors and WBCs. Further research is necessary to determine the clinical relevance of these findings.

    View details for DOI 10.1177/0363546510387517

    View details for Web of Science ID 000287025700008

    View details for PubMedID 21051428

  • Trends in serum relaxin concentration among elite collegiate female athletes. International journal of women's health Dragoo, J. L., Castillo, T. N., Korotkova, T. A., Kennedy, A. C., Kim, H. J., Stewart, D. R. 2011; 3: 19-24


    This study was designed to investigate the relationship between serum relaxin concentration (SRC) and menstrual history and hormonal contraceptive use among elite collegiate female athletes. Evaluation of SRC in athletes is necessary, because relaxin has been associated with increased knee joint laxity and decreased anterior cruciate ligament (ACL) strength in animal models.National Collegiate Athletic Association Division I female athletes participating in sports at high risk for ACL tears - basketball, field hockey, gymnastics, lacrosse, soccer, and volleyball - were invited to participate. All participants completed a questionnaire about their menstrual history and hormonal contraceptive use. Venipuncture was performed to obtain samples of serum progesterone and relaxin. Samples were obtained during the mid-luteal phase from ovulating participants, and between the actual or projected cycle days 21 to 24, from anovulatory participants. Serum concentration of relaxin and progesterone was determined by ELISA and the data were analyzed using SPSS statistical software with significance set at P = 0.05.169 female athletes participated. The mean SRC among all participants was 3.08 6.66 pg/mL). The mean SRC differed significantly between those participants using hormonal contraceptives (1.41 pg/mL) and those not using hormonal contraceptives (3.08 pg/mL, P = 0.002). Mean SRC was lowest among amenorrheic participants (1.02 pg/mL) and highest among oligomenorrheic participants (3.71 pg/mL) and eumenorrheic participants (3.06 pg/mL); these differences were not significant (P = 0.53). Mean serum progesterone concentration (SPC) differed significantly between those participants using hormonal contraceptives (2.80 ng/mL), and those not using hormonal contraceptives (6.99 ng/mL, P < 0.0001).There is a positive correlation between serum progesterone and SRC and an attenuation of SRC with hormonal contraceptive use. Our results underscore the significant role that hormonal contraceptives can play in decreasing relaxin levels, if future investigations establish a link between relaxin levels and ligamentous injury among female athletes.

    View details for DOI 10.2147/IJWH.S14188

    View details for PubMedID 21339934

  • Restoration of Knee Volume Using Selected Arthroscopic Releases AMERICAN JOURNAL OF SPORTS MEDICINE Dragoo, J. L., Miller, M. D., Vaughn, Z. D., Schmidt, J. D., Handley, E. 2010; 38 (11): 2288-2293


    Inflammation and subsequent fibrosis, adhesions, or plicae may limit normal capsular compliance and decrease volume capacity of the knee.Patients with fibrosis, anterior interval scarring, adhesions, or palpable painful plicae will have decreased knee volumes when compared to controls, and selective arthroscopic releases will restore volume to normal levels.Descriptive laboratory study and cohort study; Level of evidence, 2.In part I, knee volume and pressure were recorded in 14 fresh-frozen human cadaveric knees, and the maximum volume capacity was identified before capsular disruption. In part II, 49 patients undergoing arthroscopy were divided into 2 groups based on intraoperative volume assessment at 50 mm H(2)O pressure: group 1 (n = 20) with normal volume (<1 standard deviation below the mean established in part I) and group 2 (n = 29) knees with deficient volume (>1 standard deviation below mean). Group 2 underwent volume-changing procedures such as lysis of adhesions, anterior interval release, and plica resections, while group 1 underwent volume-neutral procedures including meniscal or chondral surgery. The knee volume was then reassessed after arthroscopy.The average volume capacity of the knees in the cadaveric study was 87.5 21.7 mL (range, 50-120 mL). There was no statistical difference between the presurgical (98.9 29.8 mL) and postsurgical volumes (99.4 29.1 mL) in group 1; P = .65. The presurgical volume in group 2 (46.1 13.0 mL) was significantly lower than group 1 (P = .001). The group 2 volume increased to 78.5 24.2 mL after surgery (P = .001), with an average change in volume of 75.5%. The mean change in volume after surgery was significantly greater in group 2 (32.3 mL) versus group 1 (0.45 mL) (P = .001). At 1-year follow-up, the mean Tegner score in the volume-compromised group 2 increased from 2.0 1.4 preoperatively to 4.0 2.0 postoperatively (P = .01), the Lysholm score increased from 45.0 24.0 preoperatively to 76.8 25.4 postoperatively (P = .003), and the average Short Form-12 quality of life score increased from 32.4 8.7 preoperatively to 45.0 11.0 postoperatively (P = .005).The average volume of the human knee in this study was between 65 and 110 mL (1 standard deviation of mean of 87.5 mL). Although patients with chronic knee pain may have pain from multiple sources, some may have diminished knee volume, and selected arthroscopic releases can restore knee volume to near-normal levels.

    View details for DOI 10.1177/0363546510378074

    View details for Web of Science ID 000283348600023

    View details for PubMedID 20807861

  • Fabrication of custom-shaped grafts for cartilage regeneration INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS Koo, S., Hargreaves, B. A., Gold, G. E., Dragoo, J. L. 2010; 33 (10): 731-737


    to create a custom-shaped graft through 3D tissue shape reconstruction and rapid-prototype molding methods using MRI data, and to test the accuracy of the custom-shaped graft against the original anatomical defect.An iatrogenic defect on the distal femur was identified with a 1.5 Tesla MRI and its shape was reconstructed into a three-dimensional (3D) computer model by processing the 3D MRI data. First, the accuracy of the MRI-derived 3D model was tested against a laser-scan based 3D model of the defect. A custom-shaped polyurethane graft was fabricated from the laser-scan based 3D model by creating custom molds through computer aided design and rapid-prototyping methods. The polyurethane tissue was laser-scanned again to calculate the accuracy of this process compared to the original defect.The volumes of the defect models from MRI and laser-scan were 537 mm3 and 405 mm3, respectively, implying that the MRI model was 33% larger than the laser-scan model. The average (SD) distance deviation of the exterior surface of the MRI model from the laser-scan model was 0.4 0.4 mm. The custom-shaped tissue created from the molds was qualitatively very similar to the original shape of the defect. The volume of the custom-shaped cartilage tissue was 463 mm3 which was 15% larger than the laser-scan model. The average (SD) distance deviation between the two models was 0.04 0.19 mm.This investigation proves the concept that custom-shaped engineered grafts can be fabricated from standard sequence 3-D MRI data with the use of CAD and rapid-prototyping technology. The accuracy of this technology may help solve the interfacial problem between native cartilage and graft, if the grafts are custom made for the specific defect. The major source of error in fabricating a 3D custom-shaped cartilage graft appears to be the accuracy of a MRI data itself; however, the precision of the model is expected to increase by the utilization of advanced MR sequences with higher magnet strengths.

    View details for Web of Science ID 000284234600006

    View details for PubMedID 21058268

  • Chondrotoxicity of Low pH, Epinephrine, and Preservatives Found in Local Anesthetics Containing Epinephrine AMERICAN JOURNAL OF SPORTS MEDICINE Dragoo, J. L., Korotkova, T., Kim, H. J., Jagadish, A. 2010; 38 (6): 1154-1159


    Recent clinical and basic science investigations have revealed the chondrotoxicity of local anesthetics, especially those containing epinephrine, administered via an intra-articular pain pump. However, the exact mechanism of toxicity is unknown. This study evaluates the chondrotoxicity of low pH, epinephrine, and preservatives found in commonly used local anesthetics.The chondrotoxicity of local anesthetics containing epinephrine is due to low pH, epinephrine, or the preservative sodium metabisulfite.Controlled laboratory study.Human chondrocytes were harvested and cultured in a custom bioreactor designed to simulate metabolism of medication. Pain pumps were used to infuse one of the following medications into the culture system: control media; media titrated to pH 4.5, 5.0, 5.5, 6.0, 6.5; media with 1:100000 or 1:200000 epinephrine only; media with 0.5 mg/mL of sodium metabisulfite preservative; media with 0.5 mg/mL of methylparaben preservative, 0.25% bupivacaine, 0.25% bupivacaine with epinephrine, 1% lidocaine, and 1% lidocaine with epinephrine. Cultures were perfused for 24 hours and then were stained with live/dead cell viability assay. The chondrocytes were then examined by fluorescence microscopy and counted, and the percentage of cell death was calculated.Cultures containing media titrated to pH 4.5 and 5.0 and local anesthetics containing epinephrine (pH 4.0-5.5) had high cell death rates compared with controls at all time points (P < .001), while cultures containing 1:100000 and 1:200000 epinephrine alone had no increased death rate. Also, 0.5 mg/mL sodium metabisulfite preservative had a significant effect on cell death (P < .034); however, the preservative methylparaben had no effect (P > .05). The percentage of cell death was not significant for 1% lidocaine (12.5%; P > .943) and 0.25% bupivacaine (16.5%; P > .609).The marked chondrotoxicity of local anesthetics containing epinephrine appears to be a combined effect of low pH, as these medications are titrated to pH 4.0 to 5.5 for product stability, and the preservative sodium metabisulfite. Extreme caution should be exercised when using intra-articular pain pumps with local anesthetics containing epinephrine.Understanding the causes of chondrotoxicity using local anesthetics containing epinephrine is critical to decrease complications associated with this class of medications.

    View details for DOI 10.1177/0363546509359680

    View details for Web of Science ID 000278062200010

    View details for PubMedID 20348285

  • Mechanics of the anterior interval of the knee using open dynamic MRI CLINICAL BIOMECHANICS Dragoo, J. L., Phillips, C., Schmidt, J. D., Scanlan, S. F., Blazek, K., Steadman, J. R., Williams, A. 2010; 25 (5): 433-437


    The anterior interval of the knee has been defined as the space between the infrapatellar fat pad and patellar tendon anteriorly, and the anterior border of the tibia and the transverse meniscal ligament posteriorly. Investigation of the normal kinematics of this region is necessary as we begin to appreciate the significant impact that pathologic processes of the anterior interval have on the knee.Non-weight bearing and weight bearing dynamic MRIs of 20 healthy knees were evaluated at 30 degrees intervals from 0 degrees to 120 degrees flexion. The angle subtended by the patellar tendon and the anterior tibia was measured at each interval of flexion by three independent observers. The amount of angular change over each interval of flexion was also evaluated and the differences between the relative weight bearing conditions were statistically evaluated.The angle formed by the anterior tibia and the patellar tendon decreases with knee flexion (45.2 degrees (SD 10.1 degrees ) at full extension vs. 1.2 degrees (SD 2.1 degrees ) at full flexion). The average patellar tendon-tibial angle excursion was significantly reduced with full-weight bearing, 43.1 degrees (SD 11.2 degrees ) from 0 degrees to 120 degrees of flexion, compared to non-weight bearing, 30.9 degrees (SD 6.1 degrees ) over the same range of motion (P<0.001). Full-weight bearing decreased the angle excursion by 28% compared to non-weight bearing.The observed changes in the anterior interval are influenced by multiple factors including load, knee architecture, tendon elasticity and tibio-femoral and patello-femoral kinematics. The impact of load on the mechanics of the anterior interval is most pronounced between 0 degrees and 30 degrees of flexion.

    View details for DOI 10.1016/j.clinbiomech.2010.01.011

    View details for Web of Science ID 000278746800008

    View details for PubMedID 20189271

  • Effect of bupivacaine on chondrocyte viability. spine journal Dragoo, J. L., Pun, S. Y. 2010; 10 (2): 172-173

    View details for DOI 10.1016/j.spinee.2009.11.015

    View details for PubMedID 20142073

  • The Effect of Playing Surface on Injury Rate A Review of the Current Literature SPORTS MEDICINE Dragoo, J. L., Braun, H. J. 2010; 40 (11): 981-990


    Synthetic playing surfaces are widely used for field and court sports. Artificial turf surfaces are commonly used as an alternative to natural grass, while outdoor surfaces like clay and acrylic are also prevalent. The effect of these synthetic surfaces on injury rates has not been clearly established. The available literature is largely limited to football and soccer data and the majority of studies are short-term. Confounding variables such as climate, player position and footwear, as well as varying definitions of injury, also make it difficult to draw firm conclusions about the general effect of artificial playing surfaces on injury rates. Many peer-reviewed studies cite a higher overall rate of injury on first- and second-generation artificial turf surfaces compared with natural grass. Despite differences in injury type, the rate of injury on third-generation and natural grass surfaces appears to be comparable. It also appears that clay is significantly safer than either grass or hard court tennis surfaces, but this is a conclusion drawn with limited data. Further research investigating overall injury trends as well as sport-specific data is needed to draw more definitive conclusions regarding the effect of artificial playing surfaces on injury rates.

    View details for Web of Science ID 000284301600006

    View details for PubMedID 20942512

  • Biomechanical Evaluation of a 1-Stage Revision Anterior Cruciate Ligament Reconstruction Technique Using a Structural Bone Void Filler for Femoral Fixation ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY Vaughn, Z. D., Schmidt, J., Lindsey, D. P., Dragoo, J. L. 2009; 25 (9): 1011-1018


    The purpose of this study was to develop a method of femoral fixation for complex revision anterior cruciate ligament (ACL) reconstructions that would avoid a staged bone grafting approach. We evaluated the use of a calcium phosphate cement as a structural bone void filler that would allow for a single-stage revision ACL reconstruction with initial biomechanical properties equivalent to standard autologous bone-patellar tendon-bone primary ACL reconstruction.We tested 11 matched pairs of fresh-frozen cadaveric knees (N = 22). Controls were treated with autologous bone-patellar tendon-bone primary ACL reconstruction fixed with bioabsorbable interference screws with a 1-mm back wall. The contralateral knee of each pair had a large bone void created that would hamper subsequent femoral fixation to simulate revision ACL reconstruction conditions. This defect was filled with calcium phosphate cement arthroscopically. After solidification, the femoral tunnel was drilled through the bone void filler and native bone with a 1-mm back wall, allowing anatomic positioning. The autologous graft was then placed and fixed with a bioabsorbable interference screw. Specimens were then tested in an MTS machine (MTS Systems, Eden Prairie, MN) for load to failure according to a standard protocol and compared with matched controls.Failure loads for the control group averaged 312 N (standard deviation [SD], 127 N) and were not significantly different compared with the calcium phosphate cement revision group, which averaged 301 N (SD, 95 N) (P = .80). Failure occurred at the femoral bone block in both groups but without screw pullout.Statistical analysis failed to show a significant difference between the control group and the group undergoing structural bone void filler revision in this biomechanical evaluation of initial fixation strength.This technique may allow surgeons to perform a single-stage revision ACL reconstruction in the presence of a contained bone void and avoid the need for a staged procedure if clinical studies verify long-term incorporation of the bone void filler.

    View details for DOI 10.1016/j.arthro.2009.04.068

    View details for Web of Science ID 000269698900018

    View details for PubMedID 19732640

  • The effect of relaxin on the female anterior cruciate ligament: Analysis of mechanical properties in an animal model KNEE Dragoo, J. L., Padrez, K., Workman, R., Lindsey, D. R. 2009; 16 (1): 69-72


    The peptide hormone relaxin, found in pregnant and non-pregnant females, has been shown to have collagenolytic effects on ligamentous tissue. Relaxin receptors have recently been identified on the human female anterior cruciate ligament (ACL). Relaxin may affect the load bearing properties of the female ACL and contribute to non-contact ACL injuries.The administration of recombinant relaxin+/-estrogen will lead to a significant decrease in ACL integrity in the guinea pig model.Controlled laboratory study.Adult female guinea pigs were divided into three experimental groups. Group 1 (n=4) was administered only 20 microg/h of recombinant porcine relaxin for 3 weeks. Group 2 (n=4) was administered 20 microg/h of recombinant porcine relaxin and 5 microg/h of estradiol for 3 weeks. Group 3 (n=4) served as both a normal control before surgical transection of the ACL and a positive ACL tear control after transection. All hormones were administered using separate implanted osmotic pumps. ACL laxity was tested by implanting radio-opaque markers in the femur and tibia of each leg. After applying a standard anterior force (22 N), the distance between markers was measured radiographically at day 0 and day 21. The animals were then sacrificed and the ACL's were analyzed for load-to-failure using a material testing machine.Load-to-failure testing indicated that animals treated with relaxin only had significantly weaker ACL's (micro=40.4 N, p=0.001) compared to controls (micro=64.1 N). The relaxin+estrogen group (micro=32.7 N) was also significantly weaker than controls (p=0.007). There were no statistical differences between relaxin and relaxin+estrogen groups. Both relaxin only and relaxin+estrogen groups showed an increase in anterior translation of the tibia after 3 weeks of infusion, but it did not achieve statistical significance.Relaxin significantly alters the mechanical properties of the ACL in an animal model.The effects of relaxin, possibly in conjunction with estrogen, may contribute to a comprehensive etiology for human female non-contact ACL injuries.

    View details for DOI 10.1016/j.knee.2008.09.005

    View details for Web of Science ID 000262743000015

    View details for PubMedID 18964043

  • College Football Player With Unstable C1 Fracture A Case Report AMERICAN JOURNAL OF SPORTS MEDICINE Bales, C. P., Chang, I., Matheson, G., Ouyang, D., Dragoo, J. L. 2009; 37 (1): 195-198

    View details for DOI 10.1177/0363546508328594

    View details for Web of Science ID 000262196300025

    View details for PubMedID 19124837

  • Disorders of the suprapatellar pouch of the knee KNEE Dragoo, J. L., Abnousi, F. 2008; 15 (5): 348-354


    Proper recognition and treatment of pathological conditions of the suprapatellar pouch of the knee is dependent on the knowledge of normal pouch anatomy and of the various conditions which affect this area of the knee and contribute to knee pain. This article includes a comprehensive review of the surgical anatomy of the pouch, current surgical techniques and review of the common conditions that have a predilection for this often overlooked area of the knee.

    View details for DOI 10.1016/j.knee.2008.02.009

    View details for Web of Science ID 000259839400002

    View details for PubMedID 18407503

  • Arthroscopic release for symptomatic scarring of the anterior interval of the knee 32nd Annual Meeting of the American-Orthopaedic-Society-for-Sports-Medicine Steadman, J. R., Dragoo, J. L., Hines, S. L., Briggs, K. K. SAGE PUBLICATIONS INC. 2008: 1763?69


    Patients with a history of knee trauma or previous surgery may exhibit pain in the infrapatellar region that is refractory to conservative care. This may be due to subtle scarring of the anterior interval.Arthroscopic release of a scarred anterior interval will lead to improvement in anterior knee pain.Case series; Level of evidence, 4.Twenty-five consecutive patients with isolated scarring of the anterior interval, confirmed with both magnetic resonance imaging (MRI) and arthroscopic examination, were included. All 25 patients had refractory anterior knee pain that was unimproved after a minimum of 6 months of physical therapy and nonsteroidal anti-inflammatory medications and pain during knee extension. All patients had a minimum of 2 previous surgical procedures, and 11 (44%) of the patients had a previous anterior cruciate ligament (ACL) reconstruction. All 25 (100%) patients had an apparent decrease in the cranial excursion of the patella and had a positive Hoffa test result. Fourteen (56%) patients had a preoperative flexion contracture of at least 5 degrees . All patients underwent an isolated arthroscopic anterior interval release.All patients were evaluated by physical examination and standardized scoring instruments with an average follow-up of 4.0 years (range, 2.0-7.2). Twenty-one patients had full range of motion of the patella in all directions and a negative Hoffa test finding at final follow-up. All 14 (100%) patients with preoperative flexion contractures (>5 degrees ) experienced a full return of extension. The average Lysholm score improved from 59 preoperatively to 81 postoperatively (P < .0001). The average International Knee Documentation Committee (IKDC) score improved from 49 to 70 (P < .001). There were no complications. Four patients (16%) had failed results and required a second surgical release. Patients with failures had significantly lower preoperative Lysholm scores (score = 40) than those who did not (score = 58) (P = .022). Three of the failures were workers' compensation cases.Scarring of the anterior interval changes the mechanics of the anterior structures of the knee and may lead to refractory anterior knee pain. Arthroscopic anterior interval release successfully provides pain relief in this patient population.

    View details for DOI 10.1177/0363546508320480

    View details for Web of Science ID 000258719700011

    View details for PubMedID 18753680

  • Healing full-thickness cartilage defects using adipose-derived stem cells TISSUE ENGINEERING Dragoo, J. L., Carlson, G., McCormick, F., Khan-Farooqi, H., Zhu, M., Zuk, P. A., Benhaim, P. 2007; 13 (7): 1615-1621


    The purpose of this study was to evaluate the use of adipose-derived stem cells (ADSCs) as a source for full-thickness cartilage repair in an animal model. Autologous ADSCs were isolated and induced with growth medium and placed in a fibrin glue scaffold and into 3-mm x 4-mm full-thickness chondral defects in rabbits with negative controls. Specimens were evaluated for early healing using immunostaining, Western blotting, reverse transcriptase polymerase chain reaction, transfection with the Lac Z gene, and quantitative assessment. Twelve of 12 (100%) articular surface defects containing tissue-engineered stem cell constructs healed with hyaline-like cartilage, versus 1 of 12 (8%) in the control group (p < .001). There was complete healing to subchondral bone in 12 of 12 experimental defects (100%), and 10 of 12 (83%) had seamless annealing to the native cartilage. Aggrecan, superficial zone protein, collagen type II messenger ribonucleic acid, and Lac-Z gene products were identified in 12 of 12 experimental specimens, which exhibited a collagen type II:I protein ratio similar to that of normal rabbit cartilage. Quantitative histologic analysis revealed an average score of 18.2 of 21 in the experimental group, compared with 10.0 in the controls (p = .001). Induced ADSCs supported in a fibrin glue matrix are a promising cell source for cartilage tissue engineering.

    View details for DOI 10.1089/ten.2006.0249

    View details for Web of Science ID 000248035500021

    View details for PubMedID 17518742

  • Anterior cruciate ligament tears and associated injuries. Topics in magnetic resonance imaging Stevens, K. J., Dragoo, J. L. 2006; 17 (5): 347-362


    Anterior cruciate ligament (ACL) tears are a commonly sustained sports injury, often occurring in association with meniscal tears and trauma to other ligamentous structures around the knee. Diagnosis can often be made clinically, but assessment may be difficult in the acute setting when there is a large joint effusion and severe pain. Plain radiographs may detect the presence of a joint effusion and any associated fractures. However, magnetic resonance imaging is vital for assessing acute knee injuries and plays an important role in deciding treatment options and planning surgical intervention. Some of the associated meniscal and ligamentous injuries can be subtle and may easily be overlooked if these structures are not scrutinized closely. This article will discuss the anatomy of the ACL and the mechanisms and initial clinical assessment of ACL injuries, and review the imaging features of ACL tears and some of the associated injuries, including the posterolateral corner structures. These associated injuries have important implications for determining treatment options and subsequent return to athletic activities.

    View details for PubMedID 17414996

  • Tissue-engineered bone from BMP-2-transduced stem cells derived from human fat PLASTIC AND RECONSTRUCTIVE SURGERY Dragoo, J. L., Lieberman, J. R., Lee, R. S., DeUgarte, D. A., Lee, Y., Zuk, P. A., Hedrick, M. H., Benhaim, P. 2005; 115 (6): 1665-1673


    Progenitor cells capable of induction into multiple mesenchymal lineages have been isolated from human liposuction aspirates. These cells, named processed lipoaspirate cells, have previously shown in vitro osteogenic capacity. The purpose of this study was to examine the in vivo bone induction capacity of bone morphogenetic protein-2 (BMP-2)-transduced processed lipoaspirate cells using adipose tissue from multiple harvest sites.Processed lipoaspirate cells extracted from human abdominal and buttock liposuction aspirates (n = 5) and from infrapatellar fat pads (n = 5) were placed in osteogenic media containing Dulbecco's Modified Eagle Medium with 10% fetal bovine serum supplemented with 50 muM ascorbic acid-2-phosphate and 10 mM beta-glycerol phosphate. Half of these cells were transfected with an adenovirus carrying the cDNA for bone morphogenetic protein-2 (adBMP-2). These transfected cells were then seeded onto collagen I matrices at a concentration of 2 x 10 cells/matrix and were placed into the hind limbs of severe combined immunodeficient mice (n = 10). Nontransfected processed lipoaspirate cells were placed in the contralateral limb as a control. After 6 weeks, specimens were analyzed by radiographs, densitometry, and hematoxylin and eosin and von Kossa staining.The average number of cells extracted from the abdominal/buttock lipoaspirates was 3.4 x 10 cells/100 ml fat aspirate and 5.5 x 10 cells per infrapatellar fat pad (average volume, 20.6 cc). All 10 BMP-2 transfected processed lipoaspirate constructs produced abundant radiographic and histologic bone. The bone was adequately mineralized and was beginning to establish a marrow cavity. There was no quantitative difference in bone production between harvest sites [mean, 2.0 +/- 0.1 aluminum units (knee) versus 2.1 +/- 0.1 aluminum units (abdomen/buttock); p = 0.14]. No bone was produced in the negative controls.Multipotential processed lipoaspirate cells can be extracted from adipose tissue harvested from liposuction aspirates or from the infrapatellar fat pad of the knee. Processed lipoaspirate cells can be transduced with the BMP-2 gene to produce abundant in vivo bone. These cells appear to be clinically useful for bone tissue engineering applications either as osteoprogenitor cells or as delivery vehicles for BMP-2.

    View details for DOI 10.1097/01.PRS.0000161459.90856.AB

    View details for Web of Science ID 000228884600026

    View details for PubMedID 15861072

  • Bacteriostatic properties of biomatrices against common orthopaedic pathogens BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Carlson, G. A., Dragoo, J. L., Samimi, B., Bruckner, D. A., Bernard, G. W., Hedrick, M., Benhaim, P. 2004; 321 (2): 472-478


    Tissue-engineered grafts for tissue regeneration include either mature or progenitor cells seeded onto biomatrices that provide shape and support for developing tissue. Popular biomaterials used in orthopaedic surgery include collagen type I, hyaluronic acid, hydroxyapatite, and polylactic polyglycolic acid (PLGA). Biomatrices with bacteriostatic properties may be beneficial in promoting tissue-engineered graft survival in patients susceptible to infection. We evaluated the bacteriostatic effects of these biomaterials on the growth of the four most common orthopaedic bacterial pathogens: Staphylococcus aureus, Staphylococcus epidermidis, beta-hemolytic Streptococcus, and Pseudomonas aeruginosa. Hyaluronic acid demonstrated the largest bacteriostatic effect on these pathogens by inhibiting bacterial growth by an average of 76.8% (p = 0.0005). Hydroxyapatite and collagen inhibited growth on average by 49.7% (p = 0.011) and 37.5% (p = 0.102), respectively. PLGA exhibited the least bacteriostasis with an average inhibition of 9.8% (NS) and actually accelerated the growth of beta-hemolytic Streptococcus and P. aeruginosa.

    View details for DOI 10.1016/j.bbrc.2004.06.165

    View details for Web of Science ID 000223140500031

    View details for PubMedID 15358200

  • Long-term results of arthroscopic resection of the distal clavicle with concomitant subacromial decompression ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY Kay, S. P., Dragoo, J. L., LEE, R. 2003; 19 (8): 805-809


    The goal of the study was to evaluate the long-term outcome of combined arthroscopic distal clavicle excision and subacromial decompression.Retrospective, long-term cohort evaluation.Twenty patients with an average follow-up of 6 years (range, 3.9 to 9 years) were reviewed. All patients had ipsilateral impingement syndrome and acromioclavicular joint disease at the time of surgery and underwent arthroscopic subacromial decompression combined with arthroscopic distal clavicle excision. All patients returned for evaluation in person, in addition to filling out a questionnaire incorporating the University of California, Los Angeles (UCLA), and Constant scoring systems. Preoperative and postoperative radiographs were available for all patients.Postoperatively, all patients had pain relief and were satisfied with the result. The average postoperative UCLA Shoulder score was 29.8 +/- 0.6, compared with 17.5 +/- 3.0 before surgery (P =.001). The Constant Shoulder score averaged 98.5 +/- 2.1 postoperatively, compared with 70.5 +/- 11.2 preoperatively (P =.001). There was 100% good to excellent results using both scoring systems. Individual components of the UCLA scoring system (pain, function, and power) all showed significant postoperative improvement (P =.001). Constant categories of pain, activities of daily living, range of motion, and power also improved. Follow-up radiographs showed maintenance of the resected distal clavicle in 19 patients. Five patients (25%) had radiographic evidence of calcific density distal to the resected clavicle but were asymptomatic.The long-term results of arthroscopic resection of the distal clavicle with concomitant subacromial decompression are uniformly good or excellent. Impingement and acromioclavicular joint disease frequently coexist and should be identified and treated concurrently.

    View details for DOI 10.1053/S0749-8063(03)00682-0

    View details for Web of Science ID 000186137900001

    View details for PubMedID 14551540

  • Relaxin receptors in the human female anterior cruciate ligament AMERICAN JOURNAL OF SPORTS MEDICINE Dragoo, J. L., Lee, R. S., Benhaim, P., Finerman, G. A., Hame, S. L. 2003; 31 (4): 577-584


    Noncontact anterior cruciate ligament injuries occur two to eight times more often in women than in men. Changes in ligament laxity and strength have been associated with female hormones such as relaxin.Relaxin receptors are present within the female anterior cruciate ligament.Controlled laboratory study.Remnants of anterior cruciate ligament were harvested from five women and five men undergoing routine ligament reconstruction. Relaxin was biotinylated and analyzed for biologic activity with use of the mouse interpubic ligament bioassay. Immunohistochemical localization of relaxin receptors was performed with appropriate negative controls and competitive binding assays to determine receptor specificity and saturability.Anterior cruciate ligament sections from women but not from men showed uniform specific binding that was limited to synovial lining cells, stromal fibroblasts, and cells lining blood vessels. Specific binding was confirmed in the presence of a 2000-fold excess of human insulin, the structural homolog of relaxin, and competitive inhibition was demonstrated in the presence of a 2000-fold excess of unlabeled relaxin.Relaxin exhibits specific saturable binding in the female anterior cruciate ligament, where specific relaxin receptors were present. Clinical Relevance: The high incidence of anterior cruciate ligament rupture in female athletes may be partially explained by the effects of relaxin.

    View details for Web of Science ID 000184237600017

    View details for PubMedID 12860548

  • Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME Dragoo, J. L., Samimi, B., Zhu, M., Hame, S. L., Thomas, B. J., Lieberman, J. R., Hedrick, M. H., Benhaim, P. 2003; 85B (5): 740-747
  • Knee function after anterior cruciate ligament injury in elite collegiate athletes AMERICAN JOURNAL OF SPORTS MEDICINE McAllister, D. R., Tsai, A. M., Dragoo, J. L., McWilliams, J., Dorey, F. J., Hame, S. L., Finerman, G. A. 2003; 31 (4): 560-563


    Anterior cruciate ligament injuries are common in athletes, but there are few studies of long-term outcomes.Long-term knee function of anterior cruciate ligament-injured athletes is inferior to that of their uninjured teammates.Retrospective cohort study.Thirty-three Division I-A athletes who had sustained an anterior cruciate ligament injury during their college career completed a series of questionnaires that assessed knee function and quality of life 2 to 14 years after injury. Their responses were compared with those of a matched cohort of their uninjured teammates.There were no differences in the mean Tegner scores, modified Lysholm scores, or in the scores of the SF-36 between groups. Sixteen anterior cruciate ligament-injured athletes scored A or B in the subjective portion of the International Knee Documentation Committee score and 17 scored C or D, whereas 24 control subjects scored A or B and 9 scored C or D, a statistically significant difference between groups. Five injured and 14 control athletes had participated at a professional or national team level after college.Quality of life of elite collegiate athletes who sustained an anterior cruciate ligament injury was not significantly different from that of their uninjured teammates, but knee function differed between groups.

    View details for Web of Science ID 000184237600014

    View details for PubMedID 12860545

  • Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads. journal of bone and joint surgery. British volume Dragoo, J. L., Samimi, B., Zhu, M., Hame, S. L., Thomas, B. J., Lieberman, J. R., Hedrick, M. H., Benhaim, P. 2003; 85 (5): 740-747


    Multipotential processed lipoaspirate (PLA) cells extracted from five human infrapatellar fat pads and embedded into fibrin glue nodules, were induced into the chondrogenic phenotype using chondrogenic media. The remaining cells were placed in osteogenic media and were transfected with an adenovirus carrying the cDNA for bone morphogenetic protein-2 (BMP-2). We evaluated the tissue-engineered cartilage and bone using in vitro techniques and by placing cells into the hind legs of five severe combined immunodeficient mice. After six weeks, radiological and histological analysis indicated that the PLA cells induced into the chondrogenic phenotype had the histological appearance of hyaline cartilage. Cells transfected with the BMP-2 gene media produced abundant bone, which was beginning to establish a marrow cavity. Tissue-engineered cartilage and bone from infrapatellar fat pads may prove to be useful for the treatment of osteochondral defects.

    View details for PubMedID 12892203

  • Bone induction by BMP-2 transduced stem cells derived from human fat JOURNAL OF ORTHOPAEDIC RESEARCH Dragoo, J. L., Choi, J. Y., Lieberman, J. R., Huang, J., Zuk, P. A., Zhang, J., Hedrick, M. H., Benhaim, P. 2003; 21 (4): 622-629


    We have isolated pluripotent mesenchymal progenitor cells in large numbers from liposuction aspirates (processed lipoaspirate cells or PLAs). This study examines the osteogenic potential of PLAs and bone marrow aspirate cells (BMAs), when exposed to either recombinant human bone morphogenetic protein (BMP)-2 (rh-BMP-2) or adenovirus containing BMP-2 cDNA (Ad-BMP-2).Liposuction aspirates underwent proteolytic digestion to obtain PLAs. After exposure to exogenous rh-BMP-2 or Ad-BMP-2 for four or seven days, PLAs and BMAs were assessed by histochemistry, spectrophotometry and RT-PCR. Western blotting and ELISA confirmed BMP gene transduction. Results were compared to osteoblasts and cells in osteogenic media only. PLA-Ad-BMP-2 cells were seeded on matrices and implanted in the hind limbs of SCID mice.Analysis of quantified bone precursor assays including extracellular ALP histomorphometry, intracellular ALP spectrophotometry, and calcified extracellular matrix (von Kossa) histomorphometry revealed that PLAs treated with exogenous rh-BMP-2 or transduced with a BMP-2 containing adenovirus (PLA-Ad-BMP-2) produced more bone precursors than osteoblasts (p=0.001). PLAs treated with exogenous rh-BMP-2 or PLA-Ad-BMP-2 also produced more bone precursors than BMAs (p=0.001), except for day 7 ALP histomorphometry (p=0.343). ELISA confirmed successful BMP-2 production by both progenitor cell groups transduced with Ad-BMP-2. H&E sections from collagen I matrices seeded with PLA-Ad-BMP-2 cells confirmed bone formation at six weeks.Liposuction aspirates contain PLAs that can be transfected with the BMP-2 gene, with rapid induction into the osteoblast phenotype at a rate comparable to rh-BMP-2 and osteoblast groups. Transduced PLAs produce more bone precursors with faster onset of calcified extracellular matrix than transduced BMAs. PLAs may be an ideal source of mesenchyme-lineage stem cells for gene therapy and tissue engineering.

    View details for DOI 10.1016/S0736-0266(02)00238-3

    View details for Web of Science ID 000183792200008

    View details for PubMedID 12798061

  • Comparison of multi-lineage cells from human adipose tissue and bone marrow CELLS TISSUES ORGANS De Ugarte, D. A., Morizono, K., Elbarbary, A., Alfonso, Z., Zuk, P. A., Zhu, M., Dragoo, J. L., Ashjian, P., Thomas, B., Benhaim, P., Chen, I., Fraser, J., Hedrick, M. H. 2003; 174 (3): 101-109


    Our laboratory has recently characterized a population of cells from adipose tissue, termed processed lipoaspirate (PLA) cells, which have multi-lineage potential similar to bone-marrow-derived mesenchymal stem cells (MSCs). This study is the first comparison of PLA cells and MSCs isolated from the same patient. No significant differences were observed for yield of adherent stromal cells, growth kinetics, cell senescence, multi-lineage differentiation capacity, and gene transduction efficiency. Adipose tissue is an abundant and easily procured source of PLA cells, which have a potential like MSCs for use in tissue-engineering applications and as gene delivery vehicles.

    View details for DOI 10.1159/000071150

    View details for Web of Science ID 000184000600001

    View details for PubMedID 12835573

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