James Chang

Abstract

Extremity injuries involving tendon attachment to bone are difficult to address. Clinically, tendon-bone interface allografts must be decellularized to reduce immunogenicity. Composite grafts are difficult to decellularize because chemical agents cannot reach cells between tissues. In this study, the authors attempted to optimize tendon-bone interface graft decellularization.Human flexor digitorum profundus tendons with attached distal phalanx were harvested from cadavers and divided into four groups. Group 1 (control) was untreated. Group 2 (chemical) was chemically treated with 5% peracetic acid, 0.1% ethylenediaminetetraacetic acid, and 0.1% sodium dodecyl sulfate. Group 3 (low-power) underwent targeted ultrasonication for 3 minutes (22,274 J, 126W) followed by chemical decellularization. Group 4 (high-power) underwent targeted ultrasonication for 10 minutes (88,490 J, 155W) followed by chemical decellularization. Decellularization was assessed histologically with hematoxylin and eosin stain and stains for major histocompatibility complex I stains. Cell counts were performed. The ultimate tensile load of decellularized grafts (group 4) were compared with pair-matched untreated grafts (group 1).Average cell counts were 100 ± 41, 27 ± 10, 12 ± 11, and 6 ± 11 per high-power field for groups 1, 2, 3, and 4, respectively (p < 0.001). Decellularization using physical and chemical treatments (groups 3 and 4) resulted in substantial reduction of cells and major histocompatibility complex I molecules. There was no difference in ultimate tensile load between treated (group4) and untreated (group 1) samples (p > 0.5).Physicochemical decellularization of tendon-bone interface grafts using targeted ultrasonication and chemical treatment resulted in near-complete reduction in cellularity and maintenance of tensile strength. In the future, these decellularized composite scaffolds may be used for reconstruction of tendon-bone injuries.

View details for DOI 10.1097/PRS.0b013e318290f5fc

View details for PubMedID 23806913

View details for DOI 10.1016/j.jhsa.2013.02.012

View details for PubMedID 23561724

Abstract

The treatment of facial palsy is a complex and challenging area of plastic surgery. Microsurgical innovation has introduced the modern age of dynamic reconstruction for facial palsy. This review will focus on microsurgical reconstruction for smile restoration in patients with long-standing facial palsy. The most common donor muscles and nerves will be presented. The advantages and disadvantages of single-stage versus multi-stage reconstruction will be discussed. Contemporary trends will be highlighted and the authors' preferred practice outlined.

View details for DOI 10.1002/micr.22042

View details for Web of Science ID 000313812600013

View details for PubMedID 22976539

View details for DOI 10.1016/j.jvs.2011.09.055

View details for Web of Science ID 000310428200043

View details for PubMedID 23083666

Abstract

Complex traumatic injuries and degenerative conditions of the hand continue to lead to significant impairment and disability. From technical innovations to regenerative concepts, this article presents the latest advances in the dynamic field of hand surgery in which worldwide efforts are made around the globe to repair, regenerate, or restore each composite tissue forming the hand. The systematic method by which finger replantation is performed, from bony fixation to skin closure, provides a platform for discussion of the newest innovations available to reconstructive hand surgeons.

View details for DOI 10.1016/j.cps.2012.07.013

View details for Web of Science ID 000311191000010

View details for PubMedID 23036295

Abstract

In patients with chronic scapholunate (SL) dissociation or dynamic instability, ligament repair is often not possible, and surgical reconstruction is indicated. The ideal graft ligament would recreate both anatomical and biomechanical properties of the dorsal scapholunate ligament (dorsal SLIL). The finger proximal interphalangeal joint (PIP joint) collateral ligament could possibly be a substitute ligament.We harvested human PIP joint collateral ligaments and SL ligaments from 15 cadaveric limbs. We recorded ligament length, width, and thickness, and measured the biomechanical properties (ultimate load, stiffness, and displacement to failure) of native dorsal SLIL, untreated collateral ligaments, decellularized collateral ligaments, and SL repairs with bone-collateral ligament-bone composite collateral ligament grafts. As proof of concept, we then reseeded decellularized bone-collateral ligament-bone composite grafts with green fluorescent protein-labeled adipo-derived mesenchymal stem cells and evaluated them histologically.There was no difference in ultimate load, stiffness, and displacement to failure among native dorsal SLIL, untreated and decellularized collateral ligaments, and SL repairs with tissue-engineered collateral ligament grafts. With pair-matched untreated and decellularized scaffolds, there was no difference in ultimate load or stiffness. However, decellularized ligaments revealed lower displacement to failure compared with untreated ligaments. There was no difference in displacement between decellularized ligaments and native dorsal SLIL. We successfully decellularized grafts with recently described techniques, and they could be similarly reseeded.Proximal interphalangeal joint collateral ligament-based bone-collateral ligament-bone composite allografts had biomechanical properties similar to those of native dorsal SLIL. Decellularization did not adversely affect material properties.These tissue-engineered grafts may offer surgeons another option for reconstruction of chronic SL instability.

View details for DOI 10.1016/j.jhsa.2012.05.020

View details for Web of Science ID 000307260200001

Abstract

Repairs of zone II flexor tendons have benefited in recent years from modifications involving suture technique and configuration. These advances, however, present new obstacles in resident training. A focused tutorial incorporating a practical, hands-on exercise and standardization of technique may offer an effective low-risk, low-cost strategy for overcoming these challenges.Plastic surgery residents (n=14) were asked to perform their preferred zone II flexor tendon repair using a tabletop exercise before and after a focused tutorial. The tutorial reviewed primary literature and presented a standardized technique. Repairs were photographed, tested for load strength, and analyzed to determine effectiveness of this teaching approach. Participants were retested at 6 months to evaluate for persistence of findings.Posttutorial repairs required higher loads to generate a 2-mm gap (p<0.001) and ultimate breakage (p<0.001). Tendon purchase and resident confidence increased significantly. Subgroup analysis demonstrated significant improvements for both junior and senior residents. Retesting at 6 months revealed that gains were maintained over time.The authors created a practical educational model to teach zone II flexor tendon repair outside of the time- and error-sensitive confines of the operating room. Analysis of resident pretutorial repairs revealed common misconceptions in suture technique, strand count, and purchase. This may in part be attributable to the multitude of suggested repair techniques, difficulty in comparing data across multiple studies, and steep learning curve. Training programs can use this hands-on teaching exercise as part of a hand surgery simulation curriculum.

View details for DOI 10.1097/PRS.0b013e3182589d06

View details for Web of Science ID 000307019700047

View details for PubMedID 22495211

Abstract

In mutilating hand injuries, tissue engineered tendon grafts may provide a reconstructive solution. We have previously described a method to decellularize cadaveric human flexor tendons while preserving mechanical properties and biocompatibility. The purpose of this study is to evaluate the immunogenicity and strength of these grafts when implanted into an immunocompetent rat model.Cadaveric human flexor tendons were divided into two groups. Group 1 was untreated, and Group 2 was decellularized by treatment with sodium dodecyl sulfate (SDS), ethylenediaminetetraacetic acid (EDTA), and peracetic acid (PAA). Both groups were then analyzed for the presence of major histocompatibility complexes by immunohistochemistry (IHC). Pair-matched tendons from each group were then placed into the dorsal subcutaneous tissue and anchored to the spinal ligaments of Wistar rats for 2 or 4 weeks, and harvested. The infiltration of B-cells and macrophages was determined using IHC. The explants where then subjected to mechanical testing to determine the ultimate tensile stress (UTS) and elastic modulus (EM). Statistical analysis was performed using a paired Student's t-test.The decellularization protocol successfully removed cells and MHC-1 complexes. At 2 weeks after implantation, there was increased infiltration of B-cells in Group 1 (untreated) compared with Group 2 (acellular), both in the capsule and tendon substance. There was improved ultimate tensile stress (UTS, 42.7 ± 8.3 vs. 22.8 ± 7.8 MPa, p<0.05) and EM (830.2 ± 206.7 vs. 421.2 ± 171.3 MPa, p<0.05) in tendons that were decellularized. At 4 weeks, there was continued B-cell infiltration in Group 1 (untreated) compared with Group 2 (acellular). There was no appreciable difference in macrophage infiltration at both time points. At 4 weeks Group 2 (acellular) demonstrated persistently greater UTS (40.5 ± 9.1 vs. 14.6 ± 4.2 MPa, p<0.05) and EM (454.05 ± 101.5 vs. 204.6 ± 91.3 MPa, p<0.05) compared with Group 1 (untreated).Human flexor tendons that were decellularized with SDS, EDTA, and PAA resulted in removal of cellular antigens and a decreased immune response when placed into Wistar rats. These grafts showed better mechanical properties at 2 and 4 weeks when compared with control tendons. Decellularization is an important step toward the use of tissue engineered flexor tendons in upper extremity reconstruction.

View details for DOI 10.1089/ten.tea.2011.0422

View details for Web of Science ID 000302137200012

View details for PubMedID 22011137

Abstract

The Andrew J. Weiland Medal is presented each year by the American Society for Surgery of the Hand and the American Foundation for Surgery of the Hand for a body of work related to hand surgery research. This essay, awarded the Weiland Medal in 2011, focuses on the clinical need for flexor tendon reconstruction and on investigations into flexor tendon biology. Reconstruction of the upper extremity is limited by 2 major problems after injury or degeneration of the flexor tendons. First, adhesions formed after flexor tendon repair can cause decreased postoperative range of motion and hand function. Second, tendon losses can result from trauma and degenerative diseases, necessitating additional tendon graft material. Tendon adhesions are even more prevalent after tendon grafting; therefore these 2 problems are interrelated and lead to considerable disability. The total costs in terms of disability and inability to return to work are enormous. In this essay, published work from the past 12 years in our basic science laboratory is summarized and presented with the common theme of using molecular techniques to understand the cellular process of flexor tendon wound healing and to create substances and materials to improve tendon repair and regeneration. These are efforts to address 2 interrelated and clinically relevant problems that all hand surgeons face in their practice.

View details for DOI 10.1016/j.jhsa.2011.12.028

View details for Web of Science ID 000301321100024

Abstract

Tissue-engineered rabbit flexor tendons reseeded with cells are stronger in vitro after culture in a bioreactor. It is not known whether this effect persists in vivo. Tenocytes from New Zealand white rabbits were seeded onto rabbit rear paw flexor tendons that were deprived of cells and exposed to cyclic strain in a bioreactor. Reseeded constructs that were kept unloaded in a medium for 5 days were used as controls. The tendons were implanted to bridge a zone II defect in the rabbit. After explantation 4 weeks later, the ultimate tensile strength (UTS) and elastic modulus (EM) were determined. Tendon constructs that were exposed to cyclic strain had significantly improved UTS and EM. Histology showed that cellularity was increased in the bioreactor tendons.

View details for DOI 10.1177/1753193411419439

View details for PubMedID 21921065

Abstract

Tissue-engineered flexor tendon grafts may allow reconstruction of severe tendon losses. One critical factor is the optimization of cell proliferation and reseeding. Use of growth factors--basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF)-1, and platelet-derived growth factor (PDGF)-BB--may improve culture conditions for human fibroblasts, tenocytes, and adipose-derived stem cells and increase repopulation of a tendon scaffold.All cell types were plated at a density of 10,000 cells per well and cultured in F12 media supplemented with varying concentrations of bFGF, IGF-1, and PDGF-BB. After 72 hours, cell proliferation was determined using the CellTiter assay. Human flexor tendon segments were acellularized and reseeded in a cell suspension of 5 × 10(5) cells/ml. After 5 days, tendon repopulation was determined using the MTS assay and histology. Statistical significance was determined with analysis of variance and a t test.For all cell types, there was enhanced proliferation with growth factors. Among single growth factors, PDGF-BB at 50 ng/ml was the most efficient stimulator of proliferation. With multiple growth factors, the optimal concentration was determined to be 5 ng/ml bFGF, 50 ng/ml IGF-1, and 50 ng/ml PDGF-BB (increase when compared with control: fibroblasts, 2.92-fold; tenocytes, 2.3-fold; and adipose-derived stem cells, 2.4-fold; p < 0.05). Tendons reseeded with this optimal combination of growth factors showed improved reseeding compared with the control group (fibroblasts, 2.01-fold; tenocytes, 1.78-fold; and adipose-derived stem cells, 1.76-fold; p < 0.05).bFGF, IGF-1, and PDGF-BB can be used to improve cellular proliferation and repopulation of an acellularized scaffold. The use of growth factors may be an important step in the tissue engineering of human flexor tendons.

View details for DOI 10.1097/PRS.0b013e31823aeb94

View details for Web of Science ID 000300240000083

View details for PubMedID 22286428

Abstract

Proper hand function relies on a combination of strength and mobility. The intricate architecture that allows for hand mobility includes the articular surfaces of joints, periarticular ligamentous structures, tendon mechanisms, and the soft-tissue envelope. These structures are subject to injury and scarring. The net effect of a variety of etiologic factors is stiffness of the hand with diminution of hand function. This article reviews the biology of healing, pertinent anatomy of the hand, and operative and nonoperative treatment of the stiff hand.

View details for DOI 10.1016/j.cps.2011.07.006

View details for Web of Science ID 000297381500006

View details for PubMedID 22032587

Abstract

Human tendon tissue engineering attempts to address the shortage of autologous tendon material arising from mutilating injuries and diseases of the hand and forearm. It is important to maximize the tissue-engineered construct's (TEC's) biomechanical properties to ensure that the construct is in its strongest possible state before reimplantation. In this study, we sought to determine the bioreactor treatment parameters that affect these properties. Using small- and large-chamber three-dimensional-construct bioreactors (SCB and LCB, respectively), we applied cyclic axial load to TECs comprising reseeded human flexor and extensor tendons of the hand. First, small-sample pilot studies using the LCB were performed on matched-paired full-length flexor tendons to establish proof of concept. Next, large-sample studies using the SCB were performed on matched-paired extensor tendon segments to determine how reseeding, load duty cycle, load magnitude, conditioning duration, and testing delay affected ultimate tensile stress (UTS) and elastic modulus (EM). We found that compared with reseeded matched-paired controls under dynamic-loading at 1.25?N per TEC for 5 days, (1) acellular TECs had lower UTS (p=0.04) and EM (p<0.01), (2) unloaded TECs had lower UTS (p=0.01) and EM (p=0.02), (3) static-loaded TECs had lower UTS (p=0.01) and EM (p<0.01), (4) TECs conditioned for 3 days had lower UTS (p=0.03) and EM (p=0.04), and (5) TECs conditioned for 8 days had higher UTS (p=0.04) and EM (p=0.01). However, TECs conditioned at higher loads (2.5?N per TEC) and lower loads (0.625?N per TEC) possessed similar UTS (p=0.83 and p=0.89, respectively) and EM (p=0.48 and p=0.89, respectively) as controls stimulated with 1.25?N per TEC. After cycle completion, there is attrition of UTS (p=0.03) and EM (p=0.04) over a 2-day period. Our study showed that the material properties of human allograft TECs can be enhanced by reseeding and dynamic-conditioning. While conditioning duration has a significant effect on material properties, the load magnitude does not. The issue of attrition in biomechanical properties with time following cycle completion must be addressed before bioreactor preconditioning can be successfully introduced as a step in the processing of these constructs for clinical application.

View details for DOI 10.1089/ten.tea.2010.0701

View details for Web of Science ID 000295155800019

View details for PubMedID 21612572

Abstract

Acellular human tendons are a candidate scaffold for tissue engineering flexor tendons of the hand. This study compared acellularization methods and their compatibility with allogeneic human cells.Human flexor tendons were pretreated with 0.1% ethylenediaminetetracetic acid (EDTA) for 4 ?h followed by 24 ?h treatments of 1% Triton X-100, 1% tri(n-butyl)phosphate, or 0.1% or 1% sodium dodecyl sulfate (SDS) in 0.1% EDTA. Outcomes were assessed histologically by hematoxylin and eosin and SYTO green fluorescent nucleic acid stains and biochemically by a QIAGEN DNeasy kit, Sircol collagen assay, and 1,9 dimethylmethylene blue glycosaminoglycan assay. Mechanical data were collected using a Materials Testing System to pull to failure tendons acellularized with 0.1% SDS. Acellularized tendons were re-seeded in a suspension of human dermal fibroblasts. Attachment of viable cells to acellularized tendon was assessed biochemically by a cell viability assay and histologically by a live/dead stain. Data are reported as mean±standard deviation.Compared with the DNA content of fresh tendons (551±212? ng DNA/mg tendon), only SDS treatments significantly decreased DNA content (1% SDS [202.8±37.4 ?ng DNA/mg dry weight tendon]; 0.1% SDS [189±104 ?ng DNA/mg tendon]). These findings were confirmed by histology. There was no decrease in glycosaminoglycans or collagen following acellularization with SDS. There was no difference in the ultimate tensile stress (55.3±19.2 [fresh] vs. 51.5±6.9 [0.1% SDS] MPa). Re-seeded tendons demonstrated attachment of viable cells to the tendon surface using a viability assay and histology.Human flexor tendons were acellularized with 0.1% SDS in 0.1% EDTA for 24 ?h with preservation of mechanical properties. Preservation of collagen and glycoaminoglycans and re-seeding with human cells suggest that this scaffold is biocompatible. This will provide a promising scaffold for future human flexor tendon tissue engineering studies to further assess biocompatibility through cell proliferation and in vivo studies.

View details for DOI 10.1089/ten.tec.2010.0457

View details for Web of Science ID 000293278600004

View details for PubMedID 21548795

Abstract

Tissue engineering of human flexor tendons combines tendon scaffolds with recipient cells to create complete cell-tendon constructs. Allogenic acellularized human flexor tendon has been shown to be a useful natural scaffold. However, there is difficulty repopulating acellularized tendon with recipient cells, as cell penetration is restricted by a tightly woven tendon matrix. The authors evaluated peracetic acid treatment in optimizing intratendinous cell penetration.Cadaveric human flexor tendons were harvested, acellularized, and divided into experimental groups. These groups were treated with peracetic acid in varying concentrations (2%, 5%, and 10%) and for varying time periods (4 and 20 hours) to determine the optimal treatment protocol. Experimental tendons were analyzed for differences in tendon microarchitecture. Additional specimens were reseeded by incubation in a fibroblast cell suspension at 1 × 10(6) cells/ml. This group was then analyzed for reseeding efficacy. A final group underwent biomechanical studies for strength.The optimal treatment protocol comprising peracetic acid at 5% concentration for 4 hours produced increased scaffold porosity, improving cell penetration and migration. Treated scaffolds did not show reduced collagen or glycosaminoglycan content compared with controls (p = 0.37 and p = 0.65, respectively). Treated scaffolds were cytotoxic to neither attached cells nor the surrounding cell suspension. Treated scaffolds also did not show inferior ultimate tensile stress or elastic modulus compared with controls (p = 0.26 and p = 0.28, respectively).Peracetic acid treatment of acellularized tendon scaffolds increases matrix porosity, leading to greater reseeding. It may prove to be an important step in tissue engineering of human flexor tendon using natural scaffolds.

View details for DOI 10.1097/PRS.0b013e318205f298

View details for Web of Science ID 000287680200011

View details for PubMedID 21364414

Abstract

The hand, by virtue of its position in space, complex anatomical composition, and characteristic biomechanical properties, is subject to a host of disease processes and traumatic injuries. This article reviews the presentation, evaluation, treatment, and outcomes of treatment in hand infections, high-pressure injection injuries, Dupuytren disease, and arthritis.

View details for DOI 10.1097/PRS.0b013e3181f44873

View details for Web of Science ID 000284832400002

View details for PubMedID 21124099

Abstract

Tissue-engineered flexor tendons could eventually be used for reconstruction of large tendon defects. The goal of this project was to examine the effect of a tissue bioreactor on the biomechanical properties of tendon constructs seeded with adipoderived stem cells (ASCs) and fibroblasts (Fs).Rabbit rear paw flexor tendons were acellularized and seeded with ASCs or Fs. A custom bioreactor applied a cyclic mechanical load of 1.25 N at 1 cycle/minute for 5 days onto the tendon constructs. Three additional groups were used as controls: fresh tendons and tendons reseeded with either ASCs or Fs that were not exposed to the bioreactor treatment and were left in stationary incubation for 5 days. We compared the ultimate tensile stress (UTS) and elastic modulus (EM) of bioreactor-treated tendons with the unloaded control tendons and fresh tendons. Comparison across groups was assessed using one-way analysis of variance with the significance level set at p<.05. Pairwise comparison between the samples was determined by using the Tukey test.The UTS and EM values of bioreactor-treated tendons that were exposed to cyclic load were significantly higher than those of unloaded control tendons. Acellularized tendon constructs that were reseeded with ASCs and exposed to a cyclic load had a UTS of 66.76 MPa and an EM of 906.68 MPa; their unloaded equivalents had a UTS of 47.90 MPa and an EM of 715.57 MPa. Similar trends were found in the fibroblast-seeded tendon constructs that were exposed to the bioreactor treatment. The bioreactor-treated tendons approached the UTS and EM values of fresh tendons. Histologically, we found that cells reoriented themselves parallel to the direction of strain in response to cyclic strain.The application of cyclic strain on seeded tendon constructs that were treated with the bioreactor helped achieve a UTS and an EM comparable with those of fresh tendons. Bioreactor pretreatment and alternative cell lines, such as ASCs and Fs, might therefore contribute to the in vitro production of strong tendon material.

View details for DOI 10.1016/j.jhsa.2010.06.020

View details for Web of Science ID 000281526400012

Abstract

Mutilating injuries of the hand and upper extremity result in tendon losses too great to be replaced by autologous grafts. The goal of this study was to use tissue engineering techniques to produce additional tendon material. We used a custom bioreactor to apply cyclic mechanical loading onto tissue-engineered tendon constructs to study ultimate tensile stress (UTS) and elastic modulus (E). Constructs used were acellularized rabbit hindpaw flexor digitorum profundus equivalents reseeded with tenocytes or left unseeded. Tendon constructs were subjected to a stretch force of 1.25 N over a 5-day course. Seeded tendon constructs that were exposed to bioreactor loading had a significantly increased UTS (71.17 +/- 14.15 N) compared to nonloaded controls (35.69 +/- 5.62 N) (p = 0.001). Similarly, seeded constructs exposed to bioreactor loading also had a significantly higher E (1091 +/- 169 MPa) compared to nonloaded controls (632 +/- 86 MPa) (p = 0.001). This study shows that cyclic loading of tendon constructs increases the UTS and elastic modulus of seeded constructs. The use of the bioreactor may therefore accelerate the in vitro production of strong, nonimmunogenic tendon material that can potentially be used clinically to reconstruct significant tendon losses.

View details for DOI 10.1089/ten.tea.2010.0032

View details for Web of Science ID 000278164800026

View details for PubMedID 20109062

Abstract

Management of flexor tendon injuries is one of the most demanding tasks in hand surgery. Despite substantial improvements in surgical technique and postoperative rehabilitation protocols, functional outcomes may still be somewhat unreliable. In the present article, the authors present complications encountered after flexor tendon repair and provide their preferred methods of prevention and treatment.

View details for DOI 10.1016/j.hcl.2009.11.004

View details for Web of Science ID 000278887200004

View details for PubMedID 20494744

Abstract

In the United States, the Emergency Medical Treatment and Active Labor Act (EMTALA) effectively requires Level I trauma centers to accept hand trauma transfers for higher level of care if capacity exists. However, patient transfer for non-medical reasons, such as ability to pay, is still perceived as a common practice. We hypothesized that EMTALA would cause selective transfer of hand patients who were underinsured or uninsured, thus, effectively burdening a Level I trauma center. A dedicated transfer center documented the demographics and outcomes of all calls for hand trauma transfers from December 2003 to September 2005. This data registry was reviewed for age, gender, race, insurance status, and length of hospital stay. This data was compared with direct admissions to the emergency room for hand emergencies during that same time period. During the 2-year time period, a total of 151 calls for EMTALA transfer were received for hand emergencies. Our institution accepted 92 of these patients for transfer. Reasons for not accepting transfer included lack of bed availability and unavailability of the on-call surgeon due to other emergency operative cases. Compared with hand emergency patients brought directly to our emergency department during the same time period, transferred patients were younger and had a shorter length of stay. Interestingly, they were very similar in terms of sex, race, and insurance status. These data suggest that the primary motivations for EMTALA hand trauma transfers are truly complexity of patient care and specialist availability. Given the often urgent nature of hand trauma surgery and the limited resources available, expansion and development of hand and microsurgery regional centers will be vital to adequately meet demand without overburdening existing centers.

View details for DOI 10.1007/s11552-009-9214-7

View details for PubMedID 19603237

Abstract

Soft tissue defects in the hand and wrist can be challenging problems for the hand surgeon. The retrograde radial forearm fasciocutaneous flap has emerged in recent years as the workhorse flap to cover many hand and wrist defects. However, recognition of the intrinsic limitations of this flap has led to the development of other alternative flaps to provide soft tissue coverage for this region. The radial artery perforator flap has many of the benefits of the radial forearm flap but minimizes the disadvantages, such as the need to sacrifice the radial artery, color and bulk mismatch of the flap and recipient tissues, and donor site appearance. In this article, we will review the indications for using the radial artery perforator flap to cover hand and wrist soft tissue defects. We will discuss the surgical anatomy, indications, operating technique, rehabilitation protocol, potential complications, and pearls and pitfalls for use of this flap for upper-extremity defects.

View details for DOI 10.1016/j.jhsa.2009.11.015

View details for Web of Science ID 000277092700023

Abstract

Tissue-engineered tendon material may address tendon shortages in mutilating hand injuries. Tenocytes from rabbit flexor tendon can be successfully seeded onto acellularized tendons that are used as tendon constructs. These constructs in vivo exhibit a population of tenocyte-like cells; however, it is not known to what extent these cells are of donor or recipient origin. Furthermore, the temporal distribution is also not known.Tenocytes from New Zealand male rabbits were cultured and seeded onto acellularized rabbit forepaw flexor tendons (n = 48). These tendon constructs were transplanted into female recipients. Tendons were examined after 3, 6, 12, and 30 weeks using fluorescent in situ hybridization to detect the Y chromosome in the male donor cells. One unseeded, acellularized allograft in each animal was used as a control.The donor male tenocytes populate the epitenon and endotenon of the grafts at greater numbers than the recipient female tenocytes at 3 and 6 weeks. The donor and recipient tenocytes are present jointly in the grafts until 12 weeks. At 30 weeks, nearly all cells are recipient tenocyte-like cells.Donor male cells survive in decreasing numbers over time until 30 weeks. The presence of cells in tissue-engineered tendon grafts has been shown in prior studies to add to the strength of the constructs in vitro. This study shows that recipient cells can migrate into and repopulate the tendon construct. Cell seeding onto tendon material may create stronger constructs that will allow the initiation of motion earlier.

View details for DOI 10.1097/PRS.0b013e3181bcf320

View details for Web of Science ID 000272615600032

View details for PubMedID 19952658

Abstract

Tissue engineering of flexor tendons requires scaffolds with adequate strength and biocompatibility. The biomechanical properties of acellularized and reseeded flexor tendon scaffolds are unknown. Acellularized tendons and reseeded constructs were tested to determine whether the treatment process had altered their biomechanical properties.Rabbit flexor tendons were acellularized using a freeze-thaw cycle followed by trypsin and Triton-X treatment. Complete acellularization of the tendon samples was confirmed by histology and by attempting to obtain viable cells by trypsin treatment of acellularized tendon. Reseeded constructs were obtained by incubating acellularized tendons in a tenocyte suspension. Tensile testing was performed to compare the ultimate tensile stress and elastic modulus of acellularized tendons and reseeded flexor tendon constructs to control flexor tendons.The treatment protocol successfully acellularized flexor tendons. No cells were seen within the tendon on histologic assessment, and no viable cells could be obtained from acellularized tendon. Acellularized tendon was successfully reseeded with tenocytes, although cell adhesion was limited to the surface of the tendon scaffold. Tensile testing showed that acellularized tendon had the same ultimate stress and elastic modulus as normal tendons. Reseeded tendons had the same elastic modulus as normal tendons, but hind-paw tendon constructs showed a decrease in ultimate stress compared with normal tendons (50.09 MPa versus 66.01 MPa, p = 0.026).Acellularized flexor tendons are a potential high-strength scaffold for flexor tendon tissue engineering. This approach of acellularization and reseeding of flexor tendons may provide additional intrasynovial graft material for hand reconstruction.

View details for DOI 10.1097/PRS.0b013e3181a65ae7

View details for Web of Science ID 000266674600018

View details for PubMedID 19483576

Abstract

The purpose of this research was to develop a tissue-engineered intrasynovial flexor tendon construct with the use of an acellularized flexor tendon scaffold repopulated with intrasynovial tendon cells. New Zealand white rabbit intrasynovial flexor tendons were acellularized by the following methods: high concentration NaCl + SDS, Trypsin/EDTA, Trypsin/EDTA + Triton X-100, Triton X-100, Triton X-100 + SDS, and freezing at -70 degrees C followed by Trypsin/EDTA + Triton X-100. Epitenon and endotenon cells were also isolated from rabbit intrasynovial tendons and expanded in culture. Acellularized tendon scaffolds were then reseeded with these cells. A subset of epitenon and endotenon cells was labeled with green and red fluorescent markers, respectively, to further characterize the preferred location of their attachment. Optimal acellularization was achieved by freezing at -70 degrees C followed by Trypsin/EDTA + Triton X-100. After reseeding, light microscopy of tendon constructs showed attachment of both epitenon and endotenon to the tendon scaffolds, with endotenon cells more likely to be found in the core of the scaffold. An intrasynovial tendon construct was developed with the use of acellularized intrasynovial tendons repopulated with intrasynovial tenocytes. These constructs grossly resemble normal intrasynovial tendons, and cells were found both on the surface and the core of the construct histologically. This new construct represents an important first step in developing a viable tissue-engineered flexor tendon.

View details for DOI 10.1682/JRRD.2008.07.0086

View details for Web of Science ID 000270475800006

View details for PubMedID 19882484

Abstract

Dupuytren's disease is characterised by nodular fibroblastic proliferation of the palmar fascia leading to contracture of the hand. Transforming growth factor beta (TGF-beta) is thought to play a role in its pathogenesis. We performed a cDNA microarray analysis of Dupuytren's diseased cord tissue with an emphasis on TGF-beta isoforms. Normal-appearing transverse ligament of the palmar fascia from adjacent to the diseased cord and palmar fascia from patients undergoing carpal tunnel release were used as controls. TGF-beta gene expression was confirmed by quantitative real-time polymerase chain reaction. Over 20 unique genes were found to be significantly up-regulated, including several previously reported genes. A dominant increase in TGF-beta2 expression was seen in the cord tissue, whereas TGF-beta1 and TGF-beta3 were found not to be significantly up-regulated. Quantitative real-time polymerase chain reaction confirmed these findings. This gene expression profile allows for further experiments that may eventually lead to gene therapy to block the development and progression of Dupuytren's disease clinically.

View details for DOI 10.1177/1753193408091352

View details for PubMedID 18694919

Abstract

Pluripotential embryonic cells may be seeded onto sutures intended for tendon repair. These cells may be influenced to adhere to suture material using adhesion substrates, and furthermore, these cells may remain in culture attached to those sutures. These cell-impregnated sutures may be useful for promoting healing of tendon repairs.Ten-centimeter segments of 4-0 sutures (FiberWire) were coated overnight with 10 microg/mL fibronectin, 10 microg/mL poly-l-lysine, or phosphate-buffered saline. The sutures were placed in dishes and covered with a suspension of C3H10T1/2 cells at concentrations of 1 x 10(6), 2 x 10(6), or 4 x 10(6) cells for 24 hours. The sutures were then placed into low adhesion polypropylene tubes with Dulbecco's modified Eagle's medium and 10% fetal bovine serum for 7 days. The presence of viable cells on these sutures was assessed by the colorimetric Alamar blue cell proliferation assay. Spectrophotometry was used to quantify the relative amount of cell proliferation across the experimental groups. The sutures were also visually inspected using phase-contrast light microscopy.Our results show that at all seeding densities (1 x 10(6), 2 x 10(6), and 4 x 10(6) cells), the suture segments coated with poly-l-lysine and fibronectin showed a significant increase in C3H10T1/2 cell adhesion. Coating the suture with poly-l-lysine increased the adherent cell number to 17% of the initial seeding concentration compared with 2% for the control. Fibronectin coating increased the number of adherent viable cells present to 6.6%.Pluripotential embryonic cells may be seeded onto sutures, adhere, and survive in culture. Coating sutures with poly-l-lysine and fibronectin offers significant improvement in retention of viable cells. This technique may be a useful adjunct for future tendon healing studies.

View details for DOI 10.1016/j.jhsa.2008.06.010

View details for Web of Science ID 000260725900015

Abstract

Mechanical manipulation of cultured tendon cells can enhance cell proliferation and matrix production. This study aims to determine the bioreactor strain patterns (amplitude, frequency, and on/off ratio) that favor cellular proliferation, promote collagen production, and maintain morphology in candidate cell lines cultured for flexor tendon tissue engineering, including multipotent stromal cells.We studied epitenon tenocytes (Es), sheath fibroblasts (Ss), bone marrow-derived mesenchymal stem cells (BMSCs), and adipoderived stem cells (ASCs). We examined the effects of 3 patterns of cyclic uniaxial strain on cell proliferation, collagen I production, and cell morphology.Adipoderived stem cells (33% adhesion) and Ss (29%) adhered more strongly to bioreactor membranes than did Es (15%) and BMSCs (7%), p=.04. Continuous cyclic strain (CCS, 8%, 1 Hz) inhibited cell proliferation (p=.01) and increased per-cell collagen production (p=.04) in all cell types. Intermittent cyclic strain (4%, 0.1 Hz, 1 hour on/5 hours off) increased proliferation in ASCs (p=.06) and Ss (p=.04). Intermittent cyclic strain (4%, 0.1 Hz, 1 hour on/2 hours off) increased total collagen production by 25% in ASCs (p=.004) and 20% in Ss (p=.05). Cyclic strain resulted in cell alignment perpendicular to the strain axis, cytoskeletal alignment, and nuclear elongation. These morphological characteristics are similar to those of tenocytes.These results demonstrate that intermittent cyclic strain can increase cell proliferation, promote collagen I production, and maintain tenocyte morphology in vitro. Use of a cell bioreactor might accelerate the in vitro stage of tendon tissue engineering.

View details for DOI 10.1016/j.jhsa.2008.04.019

View details for Web of Science ID 000260049100021

View details for PubMedID 18929207

Abstract

Computed tomographic angiography (CTA) is a noninvasive modality for evaluating the vascular system and planning treatment strategies. The goal of this study was to validate the clinical utility of CTA in assessment of suspected pediatric extremity traumatic vascular injury, prior to emergent and delayed reconstructive surgery. A retrospective review was performed of all operative patients under 18 years of age who underwent multidetector-row CTA for evaluation of suspected extremity vascular injury. Parameters investigated included age, type of injury, referral source, temporal relationship between the injury and the CTA, CTA findings, operations performed, intraoperative findings, and clinical outcome. Between January 2002 and September 2005, 10 pediatric patients (6 males/4 females; mean age 8 years old, range 3-17) sustained either blunt (N = 8) or penetrating (N = 2) trauma and underwent CTA of the upper (N = 5) or lower extremities (N = 5). A total of 30% (3/10) of patients were referred from the emergency department acutely, 50% (5/10) were referred from the inpatient wards subacutely, and 20% (2/10) were referred from the outpatient clinics electively. Half (N = 5) underwent CTA to evaluate need for vascular repair, whereas half (N = 5) underwent CTA to evaluate local vasculature for flap reconstruction. Overall, 40% (4/10) of CTA findings were normal, whereas 60% (6/10) revealed traumatic vascular injuries. Pertinent nonvascular findings included soft tissue defects (60%, 6/10), fractures (40%, 4/10), and contracture deformities (20%, 2/10). In all cases, procedures were completed without complications, and intraoperative findings confirmed those from CTA. At a mean follow-up of 28 months, all injuries have healed without complications. CTA is a reliable noninvasive modality to evaluate pediatric patients with suspected traumatic extremity vascular injury and to plan treatment strategies for both vascular repair and extremity reconstruction.

View details for DOI 10.1007/s11552-007-9081-z

View details for PubMedID 18780090

Abstract

The timing of post traumatic microsurgical lower extremity reconstruction was defined by Godina in 1986, with recommendations for flap coverage of Gustillo grade IIIb/c fractures within 72 hours of injury. Godina's study showed the highest risk of infection and flap loss in the delayed period (72 hours-90 days). Subsequent authors have also cited lower rates of flap loss and infection when repair was performed "early". However, the definition of "early" remains ambiguous. We hypothesized that definitive debridement with optimal dressing care, meticulous microsurgical treatment planning, and vessel anastomoses outside of the zone of injury would allow for delayed reconstruction with high success rates. A retrospective review of 14 lower extremity reconstructions with free flaps was undertaken over a 4-year period. All patients underwent reconstruction in the delayed (>72 hours) period. There were no flap losses and one case of late osteomyelitis. We conclude that lower extremity reconstruction can be performed safely and effectively in the "delayed" period to allow for wound debridement, stabilization of other injuries, and transfer to a microsurgical facility.

View details for DOI 10.1002/micr.20551

View details for Web of Science ID 000261229400011

View details for PubMedID 18846574

Abstract

Biophotonics and real-time imaging are novel technologies that can greatly enhance the study of complex biological processes. We applied this technology in a transgenic mouse with a luciferase reporter gene fused to a transforming growth factor-beta (TGF-beta) responsive Smad2/3-binding element to study bioluminescence after skin wounding. Two dorsal midline excisional skin wounds were made using a biopsy punch. One wound was randomized to suture closure and the other allowed to heal by secondary intention (n=8 each wound). Bioluminescence was measured at fixed time points following surgery. Phospho-Smad2/3 immunohistochemistry was performed to localize expression in skin wound samples. In vivo bioluminescence increased following skin wounding. Peak activity occurred on day 17 and was fourfold that of baseline (p<0.05). Subgroup analysis of primary and secondary healing showed that primarily sutured wounds had peak activities earlier than those with secondary healing, although this did not reach statistical significance. Intense phospho-Smad2/3 staining was found in the hair follicles. In vivo bioluminescence tracks Smad2/3-dependent TGF-beta signaling in the in vivo wound healing process. Our findings suggest that signaling increases after wound healing, which contrasts with other studies that show raised TGF-beta signaling in the initial days following wounding.

View details for DOI 10.1111/j.1524-475X.2007.00299.x

View details for Web of Science ID 000249846800019

View details for PubMedID 17971023

Abstract

After studying this article, the participant should be able to: 1. Describe the clinical features of the disease. 2. Describe the pathoanatomical structures in Dupuytren's disease. 3. Outline the various factors associated with Dupuytren's disease. 4. Describe the modalities for surgical and nonsurgical treatment of the condition. 5. Outline recent biomolecular knowledge about the basis of Dupuytren's disease.Dupuytren's disease is characterized by nodule formation and contracture of the palmar fascia, resulting in flexion deformity of the fingers and loss of hand function. The authors review the historical background, clinical features, and current therapy of Dupuytren's disease; preview treatment innovations; and present molecular data related to Dupuytren's disease. These new findings may improve screening for Dupuytren's disease and provide a better understanding of the disease's pathogenesis.

View details for DOI 10.1097/01.prs.0000278455.63546.03

View details for Web of Science ID 000207677600001

View details for PubMedID 17700106

Abstract

The purpose of this study was to compare the histological characteristics of an autogenous fascia lata graft alone and a fascia lata graft combined with a deltoid flap in the reconstruction of rotator cuff tears. Ten New Zealand white rabbits were divided into two groups. Infraspinatus tendon defects (1 x 1 cm) were created in each animal. Reconstruction consisted of either a fascia lata graft alone or a fascia lata graft combined with a distally based deltoid flap. At 3 months, tissue harvest and histological analysis was performed. Compared to the fascia lata graft alone, there was significantly increased remodeling activity and neovascularization in the group that included a deltoid flap. Also, there was pronounced interdigitation at the graft/flap interface in the latter group. A mutually beneficial relationship may exist when an autogenous fascial graft is combined with a functional deltoid flap for reconstructing large rotator cuff defects.

View details for DOI 10.1007/s00167-006-0281-9

View details for Web of Science ID 000249212700015

View details for PubMedID 17279424

Abstract

Transforming growth factor beta1 (TGF-beta1) expression correlates with scarring. A novel transgenic mouse model with a Smad2/3-responsive luciferase reporter construct (SBE-luc) has been developed. We hypothesized that bioluminescence in SBE-luc dermal fibroblasts could be measured to assess TGF-beta1 inhibition.Cultured dermal fibroblasts from SBE-luc mice were treated simultaneously with TGF-beta1 and increasing doses of either neutralizing antibody to TGF-beta (NA-TGFbeta) or SB-431542, a novel TGF-beta receptor kinase inhibitor. Fibroblasts were measured for luciferase activity. SBE-luc fibroblasts underwent Western blot analysis for collagen type I production.TGF-beta1 produced maximal luciferase activity in SBE-luc fibroblasts at 0.1 ng/mL (P < 0.05). NA-TGFbeta and SB-431542 inhibited luciferase activity in a dose-dependent fashion, with complete inhibition achieved by 0.1 microg/mL and 1 microM, respectively (P < 0.05). NA-TGFbeta and SB-431542 inhibited collagen type I production.Our in vitro results provide validation for further in vivo real-time imaging studies using the SBE-luc mouse as a novel wound-healing model.

View details for DOI 10.1097/01.sap.0000252732.25168.34

View details for Web of Science ID 000248363400017

View details for PubMedID 17667417

Abstract

Tissue-engineered tendon grafts will meet an important clinical need. To engineer tendons, we used acellularized allogeneic tendon as scaffold material. To determine the ideal cell type to seed the scaffolds, we studied in vitro characteristics of epitenon tenocytes, tendon sheath fibroblasts, bone marrow-derived mesenchymal stem cells (BMSCs), and adipoderived mesenchymal stem cells (ASCs). Subsequently, we implanted reseeded acellularized tendons in vivo as flexor tendon grafts.Tenocytes, sheath fibroblasts, BMSCs, and ASCs were obtained from adult rabbits. For all cell lines, collagen 1, 2, and 3 immunocytochemistry was performed, and proliferation was assessed by hemacytometry and senescence by beta-galactosidase staining. Flexor tendons were acellularized after harvest. Tendons were assessed by histology after in vitro reseeding with each of the cell types after 1, 4, and 8 weeks. Finally, reseeded tendons and controls were implanted in a flexor profundus tendon defect. After 6 weeks, the reseeded tendons were harvested and assessed by histology. Statistical analysis for cell proliferation was performed using analysis of variance and t-tests with Bonferroni correction.All cell types had similar collagen expression. Cell proliferation was higher in ASCs in late passage compared with early passage and in ASCs compared with epitenon tenocytes at late passage. The other cell types were similar in growth characteristics. No senescence was detected. In vitro assessment of reseeded constructs showed the presence of cells on the construct surface. In vivo assessment after implantation showed viable cells seen within the tendon architecture in all cell types.This study suggests that the four cell types may be successfully used to engineer tendons. Adipoderived mesenchymal stem cells proliferate faster in cell culture, but the cell types were similar in other respects. All could be used to successfully repopulate acellularized tendon in vivo as flexor tendon grafts.

View details for DOI 10.1016/j.jhsa.2007.02.018

View details for Web of Science ID 000246490800002

Abstract

The Emergency Medical Treatment and Active Labor Act (EMTALA) effectively requires Level I trauma centers (TC) to accept all transfers for a higher level of care if capacity exists. We hypothesized that EMTALA would burden a Level I TC by a selective referral of a poor payer mix of primarily nonoperative patients.All transfer calls (December 2003 and September 2005) to our Level I TC are handled by a dedicated transfer center. Calls were reviewed for age, surgical service requested, and outcome of request. The trauma registry was queried to compare Injury Severity Scale (ISS) score, hospital stay (LOS), operations, mortality, and payer status for transfer and primary catchment patients.In all, 821 calls were received; 77 calls were cancelled by the referring hospital and 52 were for consultation only. Of the 692 transfer requests, 534 (77%) were accepted, 134 (19%) were denied for no capacity, and only 24 (4%) were declined by TC as not clinically indicated. Transferred patients were younger (32.0 +/- 1.49 versus 38.9 +/- 0.51, p < 0.05), had similar ISS scores (13.6 +/- 0.62 versus 13.7 +/- 0.26) and LOS (7.0 +/- 0.70 versus 7.4 +/- 0.25), but were somewhat more likely to require an operation than direct admissions (58% versus 51%, p < 0.05). Although trauma (24%) and neurosurgery (24%) were the most commonly requested services, followed by orthopedics (20%), orthopedics accounted for 60% of operations on transferred patients compared with 10% to 13% for trauma and neurosurgery (mostly spine). There was no difference in the payer status of transfer and direct admit patients.Contrary to our assumptions, EMTALA patients had an identical payer mix and similar operative need compared with our primary catchment patients. They do represent a large additional patient load (20% of admissions) and differentially impact specialists, mostly operative for orthopedics and complex nonoperative care for trauma and neurosurgery. These data suggest that the primary motivations for transfer are specialist availability and complexity of care rather than financial concerns. As TCs provide backup specialty call coverage for a wide geographic area, this further supports the need for trauma systems development.

View details for DOI 10.1097/TA.0b013e31802d9716

View details for Web of Science ID 000243490100012

View details for PubMedID 17215734

Abstract

The latissimus dorsi free flap is a workhorse for extremity reconstruction. One of its benefits is a long vascular pedicle that spans the zone of injury. However, it may be difficult to adequately cover this pedicle. Direct closure may be too tight, and skin grafting over the pedicle risks exposure if graft take is poor. We report a technique in which the serratus branch of the thoracodorsal artery and its overlying fascia are harvested en bloc with the thoracodorsal artery and latissimus muscle. This provides 2 flaps on a common pedicle that can easily be rotated to allow positioning and insetting. We successfully used this technique in the reconstruction of both upper and lower extremities. The serratus fascia provides excellent padded covering and is a good bed for skin grafting. The versatility of this hybrid flap will allow its use in a range of complex reconstructive procedures.

View details for DOI 10.1097/01.sap.0000226935.52280.19

View details for Web of Science ID 000243141000021

View details for PubMedID 17197954

Abstract

Adhesion formation between the flexor tendon and its surrounding fibro-osseous sheath results in a decreased postoperative range of motion in the hand. Transforming growth factor-beta (TGF-beta) is a key cytokine in the pathogenesis of tissue fibrosis. In this study, the effects of two natural inhibitors of TGF-beta, decorin and mannose-6-phosphate, were investigated in vitro and in vivo.In the in vitro investigation, primary cell cultures from rabbit flexor tendon sheath, epitenon, and endotenon were established and each was supplemented with TGF-beta along with increasing doses of decorin or mannose-6-phosphate. Collagen-I production was measured with enzyme-linked immunosorbent assay (ELISA). For the in vivo study, rabbit zone-II flexor tendons were transected and then immediately repaired. Single intraoperative graded doses of decorin, mannose-6-phosphate, or phosphate-buffered saline solution (control) were added to the repair sites, and the forepaws were tested for the range of motion and repair strength at eight weeks postoperatively.Decorin and mannose-6-phosphate both reduced TGF-beta upregulated collagen production. Intraoperative application of low-dose mannose-6-phosphate significantly improved the range of motion of the operatively treated digits. The effect on breaking strength of the tendon repair was inconclusive.Mannose-6-phosphate is effective in reducing TGF-beta upregulated collagen production in an in vitro model. This finding correlated with our in vivo finding that a single intraoperative dose of mannose-6-phosphate improved the postoperative range of motion.

View details for DOI 10.2106/JBJS.E.00143

View details for Web of Science ID 000241769800020

Abstract

A significant problem in flexor tendon repair is the lack of suitable graft material for reconstruction. The ex vivo production of flexor tendon graft constructs requires the expansion of primary cells. Growth factors, such as platelet-derived growth factor-BB (PDGF-BB), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (bFGF), are known to promote tendon healing and tendon cell proliferation. The purpose of these experiments was to optimize tenocyte proliferation in 3 tendon cell populations using growth factor supplementation. Cells of the synovial sheath, epitenon, and endotenon were isolated from rabbit flexor digitorum profundus tendons and maintained in culture. Cell cultures were supplemented with IGF-1, PDGF-BB, and bFGF alone and in combination. The conditions used for individual growth factor supplementation were IGF-1 (10, 50, and 100 ng/mL), PDGF-BB (1, 10, and 50 ng/mL), and bFGF (0.5, 1, and 5 ng/mL). The conditions used for combinations of growth factors were IGF-1 + PDGF-BB (50 + 10 and 100 + 50 ng/mL, respectively) and IGF-1 + PDGF-BB+ bFGF (50 + 10 + 1; 50 + 10 + 5; 100 + 50 + 1; and 100 + 50 + 5 ng/mL, respectively). For all 3 tendon cell populations, proliferation at 72 h was greater in the presence of individual growth factors as compared to controls. With PDGF-BB (50 ng/mL) supplementation, mean absorbance values increased 97% (0.57 to 1.13) in S cells, 37% (0.51 to 0.70) in E cells, and 33% (0.33 to 0.44) in T cells ( p < 0.001). In addition, a synergistic effect was observed. The combination of growth factors resulted in greater proliferation as compared to maximal doses of individual growth factors. In cultures supplemented with IGF-1 (100 ng/mL) +PDGF-BB (50 ng/mL), mean absorbance increased 114% (0.57 to 1.22) in S cells, 63% (0.51 to 0.831) in E cells, and 47% (0.33 to 0.48) in T cells ( p < 0.001). IGF-1 (100 ng/mL) + PDGF-BB (50 ng/mL) + bFGF (5 ng/mL) resulted in the greatest amount of cell proliferation for all 3 tendon cell populations. The mean absorbances increased 251% in S cells, 98% in E cells, and 106% in T cells ( p < 0.001). In summary, IGF-1, PDGF-BB, and bFGF can be used in combination to maximize tenocyte proliferation. Synergism among growth factors may provide a means to facilitate tendon engineering.

View details for Web of Science ID 000239571800021

View details for PubMedID 16889523

Abstract

Soft-tissue defects of the hand and wrist are not an uncommon problem confronting the hand surgeon. Over the past 20 years the retrograde radial forearm fasciocutaneous flap has gained widespread acceptance in reconstruction of these defects. Appreciation of the inherent limitations of this workhorse flap and increased understanding of the blood supply of the upper extremity have prompted the development of several alternative pedicled forearm flaps. Aspects of surgical technique, specific limitations, and indications for the radial forearm fascial flap, the posterior interosseous artery flap, the retrograde radial artery perforator flap, and the dorsal ulnar artery flap are discussed and a reconstructive algorithm for flap selection is presented.

View details for DOI 10.1016/j.jhsa.2006.02.024

View details for Web of Science ID 000237881700026

Abstract

Hand surgeons may be faced with tissue shortages for reconstruction after trauma, tumor resection, or congenital deficiency. Tissue engineering is a developing scientific field that combines the principles of life sciences and engineering in developing biologic substitutes that will restore, maintain, or improve tissue function. This article reviews the general principles of tissue engineering as applied to musculoskeletal tissues including nerve, bone, tendon, skin, vessels, and cartilage and focuses on the application of tissue engineering that is relevant to clinical hand surgery.

View details for PubMedID 16516727

Abstract

Dupuytren's disease (DD) is characterized by fibroblastic proliferation of the palmar fascia, often leading to flexion contracture in the hand. Although there is a strong genetic component the genome-wide expression of novel genes is not known. The purpose of this study was to use DNA microarray technology to identify upregulated genes in DD.Human tissue samples were harvested from 3 patient sources: DD cord tissue (n = 20), normal-appearing adjacent control fascia (n = 15), and palmar fascia from patients having carpal tunnel release (n = 15). DNA microarray analysis was performed on amplified sample RNA. Novel genes were compared with known gene functions. A candidate gene of interest was studied further by using immunohistochemistry on DD tissue samples and controls.Several novel genes not described previously in the study of DD were upregulated significantly, including MafB, collagen type V, alpha-2 (COL5A2), collagen type VIII, alpha-1 (COL8A1), contactin I (CNTN1), and leucine-rich repeat containing 17 (LRRC17). These upregulated genes were compared with their known gene-expression profiles in other tissues and their purported functions. MafB was found to be of particular interest because of its prominent role in tissue development and cellular differentiation. MafB immunohistochemistry showed positive staining in 50% of the DD specimens but complete absence of MafB in all control tissues (adjacent control fascia, carpal tunnel fascia). Co-localization experiments with MafB and alpha-smooth muscle actin showed staining properties in similar regions but these 2 proteins were not confined solely to the same cells.Microarray analysis of DD tissue has identified significant upregulated gene expression of MafB. MafB protein also is found in Dupuytren's cords but not in control fascia. Co-localization data suggest that the association of MafB with DD is not related exclusively to myofibroblast proliferation. Because of its role in fibroblastic transformation in other models MafB and its relationship to the pathogenesis of DD deserves further study.

View details for DOI 10.1016/j.jhsa.2005.09.007

View details for Web of Science ID 000235558900007

View details for PubMedID 16473681

Abstract

Adhesion formation after flexor tendon repair remains a clinical problem. Early postoperative motion after tendon repair has been demonstrated to reduce adhesion formation while increasing tendon strength. The authors hypothesized that during mobilization, tendon cells experience mechanical shear forces that alter their biology in a fashion that reduces scar formation but also activates key genes involved in tendon healing.To test this hypothesis, primary intrinsic tenocyte cultures were established from flexor tendons of 20 Sprague-Dawley rats and sheared at 50 rpm (0.41 Pa) using a cone viscometer for 6 and 12 hours. Total RNA was harvested and compared with time-matched unsheared controls using cDNA microarrays and Northern blot analysis.Microarray analysis demonstrated that mechanical shear stress induced an overall "antifibrotic" expression pattern with decreased transcription of collagen type I and collagen type III. Shear stress down-regulated profibrotic molecules in the platelet-derived growth factor, insulin-like growth factor, and fibroblast growth factor signaling pathways. In addition, shear stress induced an overall decrease in transforming growth factor (TGF)-beta signaling pathway molecules with down-regulation of TGF-beta2, TGF-beta3, TGF-RI, and TGF-RII expression. Moreover, sheared tendon cells increased expression of matrix metalloproteinases and decreased expression of tissue inhibitors of metalloproteinase, an expression pattern consistent with an antifibrotic increase in extracellular matrix degradation. However, the authors also found up-regulation of genes implicated in tendon healing, specifically, vascular endothelial growth factor-A and several bone morphogenetic proteins. Interestingly, the known mechanoresponsive gene, TGF-beta1, also implicated in tendon healing, was differentially up-regulated by shear stress. Northern blot validation of our results for TGF-beta1, TGF-beta2, TGF-beta3, and collagen type I demonstrated direct correlation with the authors' microarray data.The authors demonstrate an overall antifibrotic expression pattern in response to shear stress in tendon cells that may provide insight into the mechanisms by which early mobilization decreases adhesion formation without impaired tendon healing.

View details for DOI 10.1097/01.prs.0000182345.86453.4f

View details for Web of Science ID 000232421100029

View details for PubMedID 16217485

Abstract

To retrospectively evaluate multi-detector row computed tomographic (CT) angiography in determining donor- and recipient-site arterial suitability for successful vascularized free-flap transplantation.The institutional review board granted approval; informed consent was waived, and the study was HIPAA compliant. Lower extremities of 20 (12 male, eight female; mean age, 51 years; range, 10-84 years) patients undergoing vascularized free-flap procedures were examined at multi-detector row CT angiography. In five patients, legs were assessed as potential fibular free-flap donors for mandibular, maxillary, or radial reconstruction. In 15 patients, legs were assessed as recipient sites for free flaps. Vascular maps obtained with volume rendering, maximum intensity projections, and curved planar reformations were generated, and assessment was made in the depiction of calf vessels and presence of stenosis, occlusion, and anatomic anomaly. Findings of CT angiography, physical examination, and surgery were compared, where applicable, and successful CT-based prediction of the surgical intervention was assessed. Immediate and long-term (>70 days) viability of the graft was assessed in all patients.CT angiography depicted the entirety of all four major calf arteries in 29 of 32 legs scanned. In three legs, external-fixation hardware obscured some segments. There were no discrepancies between CT findings and those identified at the time of surgery. Arterial abnormalities, including stenosis, occlusion, and variant anatomy, were seen in 12 lower extremities in 10 patients. Only two were suspected on the basis of physical examination findings. In five of 20 patients, CT findings resulted in changes to the surgical plan. There was a 100% immediate viability of all grafts, which remained well vascularized between 70 days and 37 months after the procedure.Multi-detector row CT angiography provides a noninvasive means of preoperatively assessing lower extremity arteries for abnormalities, which could jeopardize graft viability or pedal arterial supply after free-flap procedures.

View details for DOI 10.1148/radiol.2371040675

View details for Web of Science ID 000231968000050

View details for PubMedID 16100083

Abstract

Computed tomography angiography is a new technique that provides high-resolution, three-dimensional vascular imaging as well as excellent bone and soft tissue spatial relationships. The purpose of this study was to examine the use of computed tomography angiography in planning upper extremity reconstruction. Seventeen computed tomography angiograms were obtained in 14 patients over a 20-month period. All studies were obtained on an outpatient basis with contrast administered through a peripheral vein. All the studies demonstrated the pertinent anatomy and the intraoperative findings were as demonstrated in all cases. Information from two studies significantly altered pre-operative planning. The average charge for computed tomography angiography was 1,140 dollars, compared to 3,900 dollars for traditional angiography.

View details for DOI 10.1016/j.jhsb.2004.04.006

View details for Web of Science ID 000224045800011

Abstract

Trauma can result in either complete amputation of fingers or devascularization of parts. Microsurgical techniques have made the salvage of devascularized digits possible. Although algorithms for digital replantation and revascularization exist, these procedures remain technically difficult and tedious. In multiple digit injuries, the complexity of replantation and revascularization is significantly increased. From our combined experience, we have found many "tricks" that have optimized digital replantation. In this paper, the current indications and contraindications for digital replantation and the technique of replantation are presented with specific reference to 12 simple maneuvers designed to maximize simplicity and efficiency.

View details for PubMedID 16518109

Abstract

Sternal osteomyelitis following cardiac surgery often requires debridement and flap coverage. The VAC (vacuum-assisted closure) device has been useful in complex wound coverage. A retrospective review of a single surgeon's experience with sternal reconstruction using the VAC device as an adjunct to debridement and muscle flap reconstruction was performed.Thirteen consecutive patients over a 34-month period underwent debridement and reconstruction of sternal wounds. Eleven patients (85%) were males, and two (15%) were females. Mean age was 61 years (range: 43-73 years). Acute purulent sternal infections occurred in seven patients, while chronic sternal osteomyelitis was seen in six patients. Use of the VAC device during the perioperative period was evaluated.Of the 13 patients, the VAC device was used prior to flap closure in six patients, and after flap closure in two patients. Sternal debridement with bilateral pectoralis muscle flaps was used to reconstruct 12 patients, and one patient underwent debridement only with VAC placement. All 13 patients (100%) had complete closure of their complex wounds at an average of follow-up of 14 months.The VAC device is useful in the treatment of sternal osteomyelitis in three contexts: (1) as a temporary wound care technique preoperatively that minimizes dressing changes and prevents shear stresses of an open sternum, (2) as the sole method of wound closure in specific cases, and (3) as a technique to facilitate healing in postoperative flap reconstruction cases complicated by reinfection.

View details for Web of Science ID 000224192400016

View details for PubMedID 15383060

Abstract

Postoperative adhesions frequently compromise the success of flexor tendon repair. Manipulation of growth factors responsible for scar formation may be a method of decreasing adhesion formation. Transforming growth factor beta (TGF-beta) is a key cytokine in the pathogenesis of tissue fibrosis. The purpose of this study was to examine the effectiveness of TGF-beta neutralizing antibody in blocking TGF-beta-induced collagen I production in rabbit flexor tendons in vitro.Sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes were obtained from rabbit flexor tendons. Each cell culture was supplemented with 1 ng/mL of TGF-beta along with increasing doses of TGF-beta neutralizing antibody (0.1-2.0 microg/mL). Collagen I production was measured by enzyme-linked immunoabsorbent assay and TGF-beta bioactivity was measured by the luciferase assay. Results were compared with TGF-beta alone and unsupplemented controls.The addition of neutralizing antibody significantly reduced TGF-beta-induced collagen I production in a dose-dependent manner in all 3 cell cultures. TGF-beta bioactivity was also reduced by its neutralizing antibody.This study shows that TGF-beta inhibition through its neutralizing antibody was effective in cultured flexor tendon cells. The results encourage further experiments that use such agents to modulate flexor tendon wound healing in in vivo models in the hope of eventually blocking the effect of TGF-beta on flexor tendons clinically.

View details for PubMedID 15043894

Abstract

Flexor tendon wound healing in zone II is complicated by adhesions to the surrounding fibro-osseous sheath. These adhesions can significantly alter tendon gliding and ultimately hand function. Lactate and transforming growth factor-beta (TGF-beta) are two important mediators of wound healing that have been demonstrated to independently increase collagen production by cells of the tendon sheath, epitenon, and endotenon. This study examined the effects of lactate on TGF-beta peptide and receptor production by flexor tendon cells. Tendon sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes were isolated from rabbit flexor tendons and cultured separately. Cell cultures were supplemented with 50 mM lactate, and the expression of three TGF-beta peptide isoforms (beta1, beta2, and beta3) and three receptor isoforms (R1, R2, and R3) was quantified with enzyme-linked immunosorbent assays. TGF-beta functional activity was also assessed with the addition of tendon cell conditioned media to mink lung epithelial cells transfected with a luciferase reporter gene expression construct responsive to TGF-beta. Supplementation of the cell culture medium with lactate significantly (p < 0.05) increased the expression of all TGF-beta peptide and receptor isoforms in all three cell lines. Tendon sheath fibroblasts exhibited the greatest increases in beta1 and beta2 peptide isoform expression (30 and 23 percent, respectively), whereas endotenon tenocytes demonstrated the greatest increase in beta3 peptide expression (32 percent). Epitenon tenocytes exhibited the greatest increases in receptor isoform R1 and R2 expression (17 and 19 percent, respectively). All three tendon cell types demonstrated significant (p < 0.05) increases in TGF-beta functional activity when exposed to lactate. Epitenon tenocytes demonstrated the greatest increase in activity (>4 times control values), whereas tendon sheath fibroblasts demonstrated the highest overall levels of total TGF-beta functional activity. Lactate significantly increased TGF-beta peptide (beta1, beta2, and beta3) expression, receptor (R1, R2, and R3) expression, and functional activity, suggesting a common pathway regulating tendon cell collagen production. Modulation of lactate and TGF-beta levels may provide a means of modulating the effects of TGF-beta on adhesion formation in flexor tendon wound healing.

View details for DOI 10.1097/01.PRS.0000101529.47062.34

View details for Web of Science ID 000220063300023

View details for PubMedID 14758225

Abstract

The role of preoperative imaging prior to free fibula flap harvest remains controversial. The standard method of preoperative imaging has been arteriography. However, arteriography is associated with known risks and potential complications to the patient. Alternatives to traditional angiography have been sought to attempt to reduce these risks. CT angiography is a noninvasive imaging modality that can accurately assess the arterial and venous circulation, while providing images equal to those of traditional angiography. CT angiography was used in 7 patients prior to free fibula flap harvest. There were no complications from the CT angiogram or the fibula harvest. We describe our use of CT angiography for vascular imaging of the lower extremity prior to free fibula harvest.

View details for Web of Science ID 000220770000007

View details for PubMedID 15038017

Abstract

After studying this article, the participant should be able to: 1. Understand the anatomy and pathophysiology of scaphoid fractures. 2. Understand the risk factors for scaphoid nonunion. 3. Identify treatment options for scaphoid nonunion and their respective advantages and disadvantages. 4. Identify salvage procedures for scaphoid nonunion advanced collapse of the wrist. Scaphoid nonunion is a common but difficult problem for hand surgeons. The diagnosis of scaphoid nonunion is often delayed, and therefore, treatment must be tailored to the type of fracture, the duration of nonunion, and the presence or absence of resulting arthritis. This article reviews the diagnosis and work-up of scaphoid nonunion, classification schemes for scaphoid nonunion, and various treatment options, including internal fixation, nonvascularized and vascularized bone grafting, and salvage procedures.

View details for Web of Science ID 000220062900026

View details for PubMedID 14578801

Abstract

Hyaluronic acid (HA) has been found to play important roles in tissue regeneration and wound-healing processes. Fetal tissue with a high concentration of HA heals rapidly without scarring. The present study employed HA formed into three-dimensional strands with or without keratinocytes to treat full-thickness skin incision wounds in rats. Wound closure rates of HA strand grafts both with and without keratinocytes were substantially enhanced. The closure times of both HA grafts were less than 1 day (average 16 h), about 1/7 that of the contralateral control incisions (114 h, p <.01). Average wound areas after 10 days were HA-only graft: 0.151 mm2 +/- 0.035; HA + cell grafts: 0.143 mm2 +/- 0.036 and controls: 14.434 mm2 +/- 1.175, experimental areas were 1% of the controls (p < 0.01). Transforming growth factor (TGF) beta1 measured by immunostaining was remarkably reduced in HA-treated wounds compared to the controls. In conclusion, HA grafts appeared to produce a fetal-like environment with reduced TGF-beta1, which is known to be elevated in incipient scars. The HA strands with or without cultured cells may potentially improve clinical wound healing as well as reduce scar formation.

View details for PubMedID 14528455

Abstract

Despite technical advances in suture methods and rehabilitation protocols, challenges remain in the field of flexor tendon repair. This article reviews the state-of-the-art research in the tissue engineering of flexor tendons. These early published data will hopefully lay the foundation for molecular methods and materials that can be used to reconstruct tendons to restore normal form and function in the hand.

View details for DOI 10.1016/S0094-1298(03)00074-9

View details for Web of Science ID 000186313400009

View details for PubMedID 14621304

Abstract

Preoperative angiography is frequently used in the planning of microsurgical reconstruction. However, several potentially devastating complications can result from angiography, including arterial occlusion and pseudoaneurysm. Computed tomographic angiography is a relatively new technique that can provide detailed information about vascular anatomy as well as soft and bony tissue without the risks of traditional angiography. In addition, three-dimensional image reconstruction uniquely demonstrates anatomical relationships among blood vessels, bones, and soft tissue. Fourteen computed tomographic angiograms were obtained in 10 patients undergoing microsurgical reconstruction of the head and neck, lower extremity, or upper extremity. The average patient age was 46.9 years (range, 22 to 67 years). Charges related to the computed tomographic procedure were compared with those of conventional preoperative imaging for microsurgical repair. At our institution, the average computed tomographic angiogram charge was 1140 US dollars, whereas the average charge for traditional arteriography was 3900 US dollars. When compared with intraoperative evaluation, computed tomographic angiograms demonstrated clinically relevant surgical anatomy. No complications were noted for the radiographic procedure or after free flap reconstruction. Computed tomographic angiography provides high-resolution, three-dimensional arterial, venous, and soft-tissue imaging without the risks of traditional angiogram and at a lower cost.

View details for DOI 10.1097/01.PRS.0000070990.97274.FA

View details for Web of Science ID 000184532700016

View details for PubMedID 12900607

Abstract

Reperfusion of ischemic tissues can be associated with structural and functional injury, which is referred to as ischemia-reperfusion injury. Superoxide dismutase is an endogenous free radical scavenger that converts toxic oxygen derived free radicals to hydrogen peroxide. With the development of gene cloning technology, the potential of manipulating cells to overexpress endogenous proteins has been realized. Transgenic mice capable of overexpressing superoxide dismutase, and knockout mice in which the gene responsible for its production has been deleted, were used as a model to examine the protective effects of superoxide dismutase against ischemia-reperfusion injury. Epigastric island flaps were elevated in wild-type (control), transgenic superoxide dismutase 1, and knockout superoxide dismutase 1 mice and subjected to ischemic intervals of 0, 3, 6, 9, or 12 hours. Five animals were studied at each time point in each study group. Flap viability was assessed on postoperative day 7. Baseline wild-type flap survival was 100 percent after 3 hours of ischemia and subsequent reperfusion; survival decreased to 21 percent after 9 hours of ischemia. Transgenic mice had significantly higher flap survival than wild-type animals after 6 hours of ischemia and subsequent reperfusion (97.0 versus 85.2 percent) and after 9 hours of ischemia (82 versus 21 percent, p < 0.01). In knockout mice, there was complete flap necrosis after as little as 3 hours of ischemia. This study confirms the protective effects of superoxide dismutase against ischemia-reperfusion injury. In addition, its deficiency results in a dramatic susceptibility to ischemic injury.

View details for DOI 10.1097/01.PRS.0000034938.58120.12

View details for Web of Science ID 000180191700042

View details for PubMedID 12496586

View details for PubMedID 12239259

Abstract

Early gestation mammalian fetuses possess the remarkable ability to heal cutaneous wounds in a scarless fashion. Over the past 20 years, scientists have been working to decipher the mechanisms underlying this phenomenon. Much of the research to date has focused on fetal correlates of adult wound healing that promote fibrosis and granulation tissue formation. It is important to remember, however, that wound repair consists of a balance between tissue synthesis, deposition, and degradation. Relatively little attention has been paid to this latter component of the fetal wound healing process. In this study, we examined the ontogeny of ten matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in nonwounded fetal rat skin and fibroblasts as a function of gestational age. We used a semiquantitative polymerase chain reaction protocol to analyze these important enzymes at time points that represent both the scarless and scar-forming periods of rat gestation. The enzymes evaluated were collagenase-1 (MMP-1), stromelysin-1 (MMP-3), gelatinase A (MMP-2), gelatinase B (MMP-9), membrane-type matrix metalloproteinases (MT-MMPs) 1, 2, and 3, and TIMPs 1, 2, and 3. Results demonstrated marked increases in gene expression for MMP-1, MMP-3 and MMP-9 that correlated with the onset of scar formation in nonwounded fetal skin. Similar results were noted in terms of MMP-9 gene expression in fetal fibroblasts. These results suggest that differences in the expression of these matrix metalloproteinases may have a role in the scarless wound healing phenotype observed early in fetal rat gestation. Furthermore, our data suggest that the differential expression of gelatinase B (MMP-9) may be mediated by the fetal fibroblasts themselves.

View details for DOI 10.1097/01.PRS.0000019915.20203.EC

View details for Web of Science ID 000177332700013

View details for PubMedID 12172142

Abstract

Flexor tendon healing is complicated by adhesions to the surrounding sheath. Transforming growth factor beta (TGF-beta) is a cytokine with numerous activities related to wound healing. We examined the effects of TGF-beta-1, -2 and -3 on tendon cell proliferation and collagen production. Three separate cell lines--sheath fibroblasts, epitenon and endotenon tenocytes--were isolated from rabbit flexor tendons and cultured separately. Cell culture media was supplemented with 1 or 5 ng/mL of TGF-beta-1, -2, or -3. Cell number and collagen I and III production were measured and compared with unsupplemented control cultures. The addition of TGF-beta to cell culture media resulted in a decrease in cell number in all 3 lines that did not reach statistical significance. There was a significant increase (p <.05) in collagen I and III production with the addition of all 3 TGF-beta isoforms. Modulation of TGF-beta production may provide a mechanism to modulate adhesion formation clinically.

View details for PubMedID 12132085

Abstract

Children born with Apert acrocephalosyndactyly pose great challenges to the pediatric hand surgeon. Reconstructive dilemmas consist of shortened, deviated phalanges and extensive skin deficits following syndactyly release. We present a 10-year review of patients with Apert acrocephalosyndactyly who were treated with a simplified surgical approach. Between 1986 and 1996, 10 patients with Apert syndrome underwent reconstructive surgery of their hands. The overall strategy involved early bilateral separation of syndactylous border digits at 1 year of age, followed by sequential unilateral middle syndactyly mass separation with thumb osteotomy and bone grafting as needed. In these 10 patients, a total of 53 web spaces were released, 49 of which involved osteotomies for complex syndactyly. Only local flaps and full-thickness skin grafts from the groin were used in all cases to achieve soft-tissue coverage. To date, seven of the 53 web spaces have needed revision (revision rate, 13 percent). Eleven thumb osteotomies (nine opening wedge and two closing wedge) were performed. Bone grafts from the proximal ulna or from other digits were used in all cases. To date, none of these thumb osteotomies have needed revision. This early, simplified approach to the complex hand anomalies of Apert acrocephalosyndactyly has been successful in achieving low revision rates and excellent functional outcomes as measured by gross grasp and pinch and by patient and parent satisfaction.

View details for Web of Science ID 000173678000008

View details for PubMedID 11818821

View details for PubMedID 17585454