Bio

Bio


Dr. James Chang is currently Professor and Chief of the Division of Plastic and Reconstructive Surgery at Stanford University. Dr. Chang graduated from Stanford University with a Bachelor of Arts and Sciences with joint degrees in Biology and Economics. He spent a year as a lecturer in English at the Beijing University of Science and Technology in Beijing, People’s Republic of China. Following this, he graduated from Yale Medical School with Alpha Omega Alpha and Cum Laude honors. From 1991 to 1993, he was a Sarnoff Laboratory Research Fellow at the University of California, San Francisco Medical Center. He then completed a residency in Plastic and Reconstructive Surgery at Stanford University Medical Center. Dr. Chang was a Clinical Instructor in Orthopedic Surgery and the Hand & Microsurgery Fellow at U.C.L.A. Medical Center from 1999-2000. He is currently Professor of Plastic Surgery and Orthopedic Surgery at Stanford University Medical Center. He is also an Attending Surgeon at Lucile Salter Packard Children's Hospital and the VA Palo Alto Health Care System, where he serves as Director of the Plastic and Hand Surgery Laboratory.

His basic science research interests include modulation of Transforming Growth Factor-Beta in scarless flexor tendon wound healing and tissue engineered flexor tendon grafts for hand reconstruction. He has expertise in molecular biology and tissue engineering techniques and their applications to plastic and hand surgery research. Dr. Chang is the recipient of numerous grants including two recent multi-year Federal Merit Review Awards on “Tissue Engineered Flexor Tendon Grafts for Extremity Reconstruction” and “Optimization of Bioengineered Tendons Using Bioreactors and Stem Cells”.

Dr. Chang is the past Editor-in-Chief of the Yearbook of Hand Surgery and an Associate Editor for the journals, Journal of Hand Surgery, Annals of Plastic Surgery, Hand, and Microsurgery. He was the Royal College of Surgeons Foundation traveling fellow and was awarded the 2006 Sterling Bunnell Traveling Fellowship by the American Society for Surgery of the Hand. He was Research Director for the American Society for Surgery of the Hand (ASSH) and managed the grant portfolio and programs of this national organization. He is currently Treasurer for the ASSH. Dr. Chang is a member of the Plastic Surgery Residency Review Committee of the ACGME and the American Board of Plastic Surgery. He was elected to the American Surgical Association in 2010.

Dr. Chang's main surgical interests are in reconstructive surgery of the hand and extremities including microsurgical reconstruction. He also has interest in pediatric hand and microsurgery, post-oncologic head and neck reconstruction, and lower extremity reconstruction.

Clinical Focus


  • Hand and Upper Extremity Surgery
  • Carpal Tunnel Syndrome
  • Hand Scleroderma
  • Microvascular Hand Surgery
  • Dupuytrens Disease
  • Peripheral Nerve Injuries
  • Facial Nerve Injuries
  • Tendon Transfer
  • Pediatric Hand Problems
  • Thumb Reconstruction
  • Free Flap Reconstruction
  • Hand Deformities
  • Microsurgery
  • Facial Paralysis
  • Hand Tumors
  • Hand Arthritis
  • Complex Reconstruction
  • Hand Fractures
  • Plastic and Reconstructive Surgery
  • Lower Extremity Reconstruction
  • Plastic Surgery

Academic Appointments


Administrative Appointments


  • Chief, Division of Plastic & Reconstructive Surgery (2006 - Present)
  • Undergraduate Advisor, Stanford University (2004 - Present)
  • Treasurer, American Society for Surgery of the Hand (2011 - 2014)
  • Board Member, American Board of Plastic Surgery (2010 - Present)
  • Plastic Surgery Residency Review Committee Member, Accreditation Council on Graduate Medical Education (2010 - Present)
  • Program Director, Plastic Surgery, Stanford University Medical Center (1999 - 2008)
  • Research Director, American Society for Surgery of the Hand (2007 - 2010)
  • Board of Directors, American Association for Hand Surgery (2007 - 2009)
  • Editor, Yearbook of Hand Surgery (2005 - 2009)
  • Associate Editor, Journal of Hand Surgery (2003 - Present)
  • Associate Editor, Annals of Plastic Surgery (2007 - Present)
  • Associate Editor, Microsurgery (2002 - 2010)
  • Associate Editor, Hand (2006 - Present)

Honors & Awards


  • Andrew J. Weiland Medal for Research Achievement, American Society for Surgery of the Hand (2011)
  • Stanford University Asian-American Faculty Award, Stanford University (2011)
  • Sterling Bunnell Traveling Fellow, American Society for Surgery of the Hand (2006-07)
  • Royal College of Surgeons Foundation Traveling Lectureship, Royal College of Surgeons (2003)
  • Leslie M. Hovey Teacher of the Year Award, Stanford Plastic Surgery (2003)
  • Scholarship Essay Award – First Place, Plastic Surgery Educational Foundation (1999)

Professional Education


  • Medical Education:Yale University School of Medicine (1993) CT
  • Residency:Stanford University School of Medicine (1998) CA
  • Internship:Stanford University School of Medicine (1994) CA
  • Fellowship:UCLA Medical Center (2000) CA
  • Board Certification: Plastic Surgery, American Board of Plastic Surgery (1999)
  • Board Certification: Surgery of the Hand, American Board of Plastic Surgery (2002)
  • MD, Yale Medical School, Medicine (1993)
  • BAS, Stanford University, Biology & Economics (1987)

Community and International Work


  • Resurge International

    Topic

    Reconstructive Surgery Abroad

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Stanford-Cambodia Hand Surgery

    Topic

    Hand Surgery

    Partnering Organization(s)

    Takeo Hospital

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


My role in research is to apply novel advances in tissue engineering and microsurgery to the clinical problems of hand trauma, peripheral nerve injuries, and congenital hand problems. I am interested in developing new tissues and techniques that will allow optimal reconstruction of form and function to those patients requiring reconstructive surgery.

Teaching

2013-14 Courses


Postdoctoral Advisees


Publications

Journal Articles


  • Physicochemical decellularization of composite flexor tendon-bone interface grafts. Plastic and reconstructive surgery Bronstein, J. A., Woon, C. Y., Farnebo, S., Behn, A. W., Schmitt, T., Pham, H., Castillo, A. B., Chang, J. 2013; 132 (1): 94-102

    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

  • Management of the hand in systemic sclerosis. journal of hand surgery Fox, P., Chung, L., Chang, J. 2013; 38 (5): 1012-1016

    View details for DOI 10.1016/j.jhsa.2013.02.012

    View details for PubMedID 23561724

  • Microsurgical reconstruction of the smilecontemporary trends MICROSURGERY Momeni, A., Chang, J., Khosla, R. K. 2013; 33 (1): 69-76

    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

  • Idiopathic true brachial artery aneurysm in an 18-month-old girl JOURNAL OF VASCULAR SURGERY Greenberg, J. I., Salamone, L., Chang, J., Harris, E. J. 2012; 56 (5): 1426-1426

    View details for DOI 10.1016/j.jvs.2011.09.055

    View details for Web of Science ID 000310428200043

    View details for PubMedID 23083666

  • New Concepts and Technologies in Reconstructive Hand Surgery CLINICS IN PLASTIC SURGERY Schmitt, T., Talley, J., Chang, J. 2012; 39 (4): 445-?

    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

  • Tissue-engineered Collateral Ligament Composite Allografts for Scapholunate Ligament Reconstruction: An Experimental Study JOURNAL OF HAND SURGERY-AMERICAN VOLUME Endress, R., Woon, C. Y., Farnebo, S. J., Behn, A., Bronstein, J., Pham, H., Yan, X., Gambhir, S. S., Chang, J. 2012; 37A (8): 1529-1537

    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

  • Overcoming the Learning Curve: A Curriculum-Based Model for Teaching Zone II Flexor Tendon Repairs PLASTIC AND RECONSTRUCTIVE SURGERY Bari, A. S., Woon, C. Y., Pridgen, B., Chang, J. 2012; 130 (2): 381-388

    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

  • Human Flexor Tendon Tissue Engineering: Decellularization of Human Flexor Tendons Reduces Immunogenicity In Vivo TISSUE ENGINEERING PART A Raghavan, S. S., Woon, C. Y., Kraus, A., Megerle, K., Choi, M. S., Pridgen, B. C., Pham, H., Chang, J. 2012; 18 (7-8): 796-805

    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

  • Studies in Flexor Tendon Reconstruction: Biomolecular Modulation of Tendon Repair and Tissue Engineering JOURNAL OF HAND SURGERY-AMERICAN VOLUME Chang, J. 2012; 37A (3): 552-561

    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

  • Bioreactor optimization of tissue engineered rabbit flexor tendons in vivo. The Journal of hand surgery, European volume Thorfinn, J., Angelidis, I. K., Gigliello, L., Pham, H. M., Lindsey, D., Chang, J. 2012; 37 (2): 109-114

    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

  • Optimization of Human Tendon Tissue Engineering: Synergistic Effects of Growth Factors for Use in Tendon Scaffold Repopulation PLASTIC AND RECONSTRUCTIVE SURGERY Raghavan, S. S., Woon, C. Y., Kraus, A., Megerle, K., Hung Pham, H., Chang, J. 2012; 129 (2): 479-489

    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

  • Functional Reconstruction of the Hand: The Stiff Joint CLINICS IN PLASTIC SURGERY Watt, A. J., Chang, J. 2011; 38 (4): 577-?

    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

  • Three-Dimensional-Construct Bioreactor Conditioning in Human Tendon Tissue Engineering TISSUE ENGINEERING PART A Woon, C. Y., Kraus, A., Raghavan, S. S., Pridgen, B. C., Megerle, K., Pham, H., Chang, J. 2011; 17 (19-20): 2561-2572

    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

  • Flexor Tendon Tissue Engineering: Acellularization of Human Flexor Tendons with Preservation of Biomechanical Properties and Biocompatibility TISSUE ENGINEERING PART C-METHODS Pridgen, B. C., Woon, C. Y., Kim, M., Thorfinn, J., Lindsey, D., Hung Pham, H., Chang, J. 2011; 17 (8): 819-828

    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

  • Optimization of Human Tendon Tissue Engineering: Peracetic Acid Oxidation for Enhanced Reseeding of Acellularized Intrasynovial Tendon PLASTIC AND RECONSTRUCTIVE SURGERY Woon, C. Y., Pridgen, B. C., Kraus, A., Bari, S., Pham, H., Chang, J. 2011; 127 (3): 1107-1117

    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

  • Joint Arthritis and Soft-Tissue Problems of the Hand PLASTIC AND RECONSTRUCTIVE SURGERY Watt, A. J., Shin, A. Y., Vedder, N. B., Chang, J. 2010; 126 (6): 288E-300E

    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

  • Tissue Engineering of Flexor Tendons: The Effect of a Tissue Bioreactor on Adipoderived Stem Cell-Seeded and Fibroblast-Seeded Tendon Constructs JOURNAL OF HAND SURGERY-AMERICAN VOLUME Angelidis, I. K., Thorfinn, J., Connolly, I. D., Lindsey, D., Pham, H. M., Chang, J. 2010; 35A (9): 1466-1472

    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

  • Flexor Tendon Tissue Engineering: Bioreactor Cyclic Strain Increases Construct Strength TISSUE ENGINEERING PART A Saber, S., Zhang, A. Y., Ki, S. H., Lindsey, D. P., Smith, R. L., Riboh, J., Pham, H., Chang, J. 2010; 16 (6): 2085-2090

    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

  • Complications After Flexor Tendon Injuries HAND CLINICS Momeni, A., Grauel, E., Chang, J. 2010; 26 (2): 179-?

    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

  • Demographic and Financial Analysis of EMTALA Hand Patient Transfers. Hand (New York, N.Y.) Melkun, E. T., Ford, C., Brundage, S. I., Spain, D. A., Chang, J. 2010; 5 (1): 72-76

    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

  • Radial Artery Perforator Flap JOURNAL OF HAND SURGERY-AMERICAN VOLUME Ho, A. M., Chang, J. 2010; 35A (2): 308-311

    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

  • Flexor Tendon Tissue Engineering: Temporal Distribution of Donor Tenocytes versus Recipient Cells PLASTIC AND RECONSTRUCTIVE SURGERY Thorfinn, J., Saber, S., Angelidis, I. K., Ki, S. H., Zhang, A. Y., Chong, A. K., Pham, H. M., Lee, G. K., Chang, J. 2009; 124 (6): 2019-2026

    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

  • Flexor Tendon Tissue Engineering: Acellularized and Reseeded Tendon Constructs PLASTIC AND RECONSTRUCTIVE SURGERY Chong, A. K., Riboh, J., Smith, R. L., Lindsey, D. P., Pham, H. M., Chang, J. 2009; 123 (6): 1759-1766

    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

  • Tissue-engineered intrasynovial tendons: Optimization of acellularization and seeding JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT Zhang, A. Y., Bates, S. J., Morrow, E., Pham, H., Pham, B., Chang, J. 2009; 46 (4): 489-497

    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

  • Gene expression analysis of Dupuytren's disease: the role of TGF-beta2. The Journal of hand surgery, European volume Zhang, A. Y., Fong, K. D., Pham, H., Nacamuli, R. P., Longaker, M. T., Chang, J. 2008; 33 (6): 783-790

    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

  • Bioactive Sutures for Tendon Repair: Assessment of a Method of Delivering Pluripotential Embryonic Cells JOURNAL OF HAND SURGERY-AMERICAN VOLUME Yao, J., Korotkova, T., Riboh, J., Chong, A., Chang, J., Smith, R. L. 2008; 33A (9): 1558-1564

    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

  • Optimization of Flexor Tendon Tissue Engineering With a Cyclic Strain Bioreactor JOURNAL OF HAND SURGERY-AMERICAN VOLUME Riboh, J., Chong, A. K., Pham, H., Longaker, M., Jacobs, C., Chang, J. 2008; 33A (8): 1388-1396

    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

  • CT angiography in pediatric extremity trauma: preoperative evaluation prior to reconstructive surgery. Hand (New York, N.Y.) Hsu, C. S., Hellinger, J. C., Rubin, G. D., Chang, J. 2008; 3 (2): 139-145

    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

  • THE TIMING OF MICROSURGICAL RECONSTRUCTION IN LOWER EXTREMITY TRAUMA MICROSURGERY Karanas, Y. L., Nigriny, J., Chang, J. 2008; 28 (8): 632-634

    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

  • Live imaging of Smad2/3 signaling in mouse skin wound healing WOUND REPAIR AND REGENERATION Chong, A. K., Satterwhite, T., Pham, H. M., Costa, M. A., Luo, J., Longaker, M. T., Wyss-Coray, T., Chang, J. 2007; 15 (5): 762-766

    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

  • Dupuytren's Disease: History, Diagnosis, and Treatment PLASTIC AND RECONSTRUCTIVE SURGERY Shaw, R. B., Chong, A. K., Zhang, A., Hentz, V. R., Chang, J. 2007; 120 (3): 44E-54E

    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

  • Deltoid flap combined with fascia lata autograft for rotator cuff defects: a histologic study KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY McAdams, T. R., Knudsen, K. R., Yalamanchi, N., Chang, J., Goodman, S. B. 2007; 15 (9): 1144-1149

    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

  • In vitro analysis of transforming growth factor-beta 1 inhibition in novel Transgenic SBE-luciferase mice ANNALS OF PLASTIC SURGERY Satterwhite, T. S., Chong, A. K., Luo, J., Pham, H., Costa, M., Longaker, M. T., Wyss-Coray, T., Chang, J. 2007; 59 (2): 207-213

    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

  • A comparison of tenocytes and mesenchymal stem cells for use in flexor tendon tissue engineering JOURNAL OF HAND SURGERY-AMERICAN VOLUME Kryger, G. S., Chong, A. K., Costa, M., Pham, H., Bates, S. J., Chang, J. 2007; 32A (5): 597-605

    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

  • Requests for 692 transfers to an academic Level I trauma center: Implications of the Emergency Medical Treatment and Active Labor Act JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE Spain, D. A., Bellino, M., Kopelman, A., Chang, J., Park, J., Gregg, D. L., Brundage, S. I. 2007; 62 (1): 63-67

    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

  • Optimization of microsurgery - Improved coverage of the Latissimus dorsi vascular pedicle with vascularized serratus fascia ANNALS OF PLASTIC SURGERY Riboh, J., Nigriny, J., Chong, A., Page, R., Chang, J. 2007; 58 (1): 109-111

    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

  • Mannose-6-phosphate, an inhibitor of transforming growth factor-beta, improves range of motion after flexor tendon repair. journal of bone and joint surgery. American volume Bates, S. J., Morrow, E., Zhang, A. Y., Pham, H., Longaker, M. T., Chang, J. 2006; 88 (11): 2465-2472

    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 PubMedID 17079405

  • Tissue engineering of flexor tendons: Optimization of tenocyte proliferation using growth factor supplementation TISSUE ENGINEERING Costa, M. A., Wu, C., Pham, B. V., Chong, A. K., Pham, H. M., Chang, J. 2006; 12 (7): 1937-1943

    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

  • Reconstruction of hand soft-tissue defects: Alternatives to the radial forearm fasciocutaneous flap JOURNAL OF HAND SURGERY-AMERICAN VOLUME Page, R., Chang, J. 2006; 31A (5): 847-856

    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

  • Tissue engineering for the hand surgeon: a clinical perspective. journal of hand surgery Chong, A. K., Chang, J. 2006; 31 (3): 349-358

    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

  • Expression of a novel gene, MafB, in Dupuytren's disease JOURNAL OF HAND SURGERY-AMERICAN VOLUME Lee, L. C., Zhang, A. Y., Chong, A. K., Pham, H., Longaker, M. T., Chang, J. 2006; 31A (2): 211-218

    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

  • Microarray analysis of mechanical shear effects on flexor tendon cells PLASTIC AND RECONSTRUCTIVE SURGERY Fong, K. D., Trindade, M. C., Wang, Z., Nacamuli, R. P., Pham, H., Fang, T. D., Song, H. J., Smith, L., Longaker, M. T., Chang, J. 2005; 116 (5): 1393-1404

    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

  • Vascular mapping of the leg with multi-detector row CT angiography prior to free-flap transplantation RADIOLOGY Chow, L. C., Napoli, A., Klein, M. B., Chang, J., Rubin, G. D. 2005; 237 (1): 353-360

    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

  • CT angiography in complex upper extremity reconstruction. Journal of hand surgery (Edinburgh, Scotland) Bogdan, M. A., Klein, M. B., Rubin, G. D., McAdams, T. R., Chang, J. 2004; 29 (5): 465-469

    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 PubMedID 15336751

  • Twelve simple maneuvers to optimize digital replantation and revascularization. Techniques in hand & upper extremity surgery Chang, J., Jones, N. 2004; 8 (3): 161-166

    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

  • Sternal osteomyelitis: Use of vacuum-assisted closure device as an adjunct to definitive closure with sternectomy and muscle flap reconstruction JOURNAL OF CARDIAC SURGERY Scholl, L., Chang, E., Reitz, B., Chang, J. 2004; 19 (5): 453-461

    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

  • Inhibition of TGF-beta-induced collagen production in rabbit flexor tendons. journal of hand surgery Zhang, A. Y., Pham, H., Ho, F., Teng, K., Longaker, M. T., Chang, J. 2004; 29 (2): 230-235

    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

  • Flexor tendon wound healing in vitro: Lactate up-regulation of TGF-beta expression and functional activity PLASTIC AND RECONSTRUCTIVE SURGERY Yalamanchi, N., Klein, M. B., Pham, H. M., Longaker, M. T., Chang, J. 2004; 113 (2): 625-632

    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

  • Preoperative CT angiography for free fibula transfer MICROSURGERY Karanas, Y. L., Antony, A., Rubin, G., Chang, J. 2004; 24 (2): 125-127

    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

  • Scaphoid nonunion: Diagnosis and treatment PLASTIC AND RECONSTRUCTIVE SURGERY Pao, V. S., Chang, J. 2003; 112 (6): 1666-1676

    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

  • Three-dimensional hyaluronic acid grafts promote healing and reduce scar formation in skin incision wounds. Journal of biomedical materials research. Part B, Applied biomaterials Hu, M., Sabelman, E. E., Cao, Y., Chang, J., Hentz, V. R. 2003; 67 (1): 586-592

    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

  • Tissue engineering of flexor tendons CLINICS IN PLASTIC SURGERY Zhang, A. Y., Chang, J. 2003; 30 (4): 565-?

    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

  • Early experience with computed tomographic angiography in microsurgical reconstruction PLASTIC AND RECONSTRUCTIVE SURGERY Klein, M. B., Karanas, Y. L., Chow, L. C., Rubin, G. D., Chang, J. 2003; 112 (2): 498-503

    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

  • Protective effects of superoxide dismutase against ischemia-reperfusion injury: Development and application of a transgenic animal model PLASTIC AND RECONSTRUCTIVE SURGERY Klein, M. B., Chan, P. H., Chang, J. 2003; 111 (1): 251-255

    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

  • Images in clinical medicine. Ulnar-nerve schwannoma. New England journal of medicine Chang, J., Klein, M. B. 2002; 347 (12): 903-?

    View details for PubMedID 12239259

  • Matrix metalloproteinases and the ontogeny of scarless repair: The other side of the wound healing balance PLASTIC AND RECONSTRUCTIVE SURGERY Peled, Z. M., Phelps, E. D., Updike, D. L., Chang, J., Krummel, T. M., Howard, E. W., Longaker, M. T. 2002; 110 (3): 801-811

    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

  • Flexor tendon healing in vitro: effects of TGF-beta on tendon cell collagen production. journal of hand surgery Klein, M. B., Yalamanchi, N., Pham, H., Longaker, M. T., Chang, J. 2002; 27 (4): 615-620

    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

  • Reconstruction of the hand in Apert syndrome: A simplified approach PLASTIC AND RECONSTRUCTIVE SURGERY Chang, J., Danton, T. K., Ladd, A. L., Hentz, V. R. 2002; 109 (2): 465-470

    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

  • Overhealing, underhealing, and skin regeneration: a new perspective on wound healing. Asian journal of surgery Peled, Z. M., Galiano, R., Chin, G. S., Chang, J., Krummel, T. M., Longaker, M. T. 2002; 25 (1): 102-110

    View details for PubMedID 17585454

  • Acute nerve grafting in traumatic injuries: Two case studies ANNALS OF PLASTIC SURGERY Sud, V., Chang, J., Lineaweaver, W. 2001; 47 (5): 555-559

    Abstract

    Primary nerve grafting in traumatic injuries is rarely performed because of the uncertainty of the extent of injury, the limited availability of nerve grafts, and the damage to adjacent soft tissue. In this report the authors present two cases of acute nerve grafting after trauma-the first of the common peroneal nerve and the second of the ulnar nerve above the elbow-with sensory and motor recovery. Although compelling general arguments against primary posttraumatic nerve grafting exist, these cases illustrate that, in certain favorable and critical clinical situations, acute nerve grafting may be successful.

    View details for Web of Science ID 000172105100015

    View details for PubMedID 11716270

  • Fetal wound healing: Progress report and future directions SURGERY Longaker, N. T., Peled, Z. M., Chang, J., Krummel, T. M. 2001; 130 (5): 785-787

    View details for Web of Science ID 000172026000002

    View details for PubMedID 11685186

  • Gene expression of transforming growth factor beta isoforms in interposition nerve grafting JOURNAL OF HAND SURGERY-AMERICAN VOLUME Karanas, Y. L., Bogdan, M. A., Lineaweaver, W. C., Hentz, V. R., Longaker, M. T., Chang, J. 2001; 26A (6): 1082-1087

    Abstract

    Scar production and neuroma formation at nerve graft coaptation sites may limit axonal regeneration and impair functional outcome. Transforming growth factor beta (TGF-beta) is a family of growth factors that is involved in scar formation, wound healing, and nerve regeneration. Fifteen adult Sprague-Dawley rats underwent autogenous nerve grafting. The nerve grafts were analyzed by in situ hybridization to determine the temporal and spatial expression of TGF-beta1 and TGF-beta3 messenger RNA (mRNA). The grafted nerves showed increased expression of TGF-beta1 and TGF-beta3 mRNA in the nerve and the surrounding connective tissue during the first postoperative week. These data suggest that modulation of TGF-beta levels in the first postoperative week may be effective in helping to control scar formation and improve nerve regeneration.

    View details for Web of Science ID 000172412500014

  • The ontogeny of scarless healing II: EGF and PDGF-B gene expression in fetal rat skin and fibroblasts as a function of gestational age ANNALS OF PLASTIC SURGERY Peled, Z. M., Rhee, S. J., HSU, M., Chang, J., Krummel, T. M., Longaker, M. T. 2001; 47 (4): 417-424

    Abstract

    Twenty years ago, surgeons noted the ability of early-gestation fetal skin to heal in a scarless manner. Since that time, numerous investigators have attempted to elucidate the mechanisms behind this phenomenon. As a result of this effort, it is now well established that many animals undergo a transition late in development from scarless cutaneous healing to a scar-forming, adultlike phenotype. The authors have been interested in the role played by cytokines known to be involved in the adult wound-healing process and how they relate to scarless repair. They therefore asked the following question: Are genes for epidermal growth factor (EGF) and platelet-derived growth factor-B (PDGF-B) expressed differentially as a function of gestational age in fetal rat skin and dermal fibroblasts? To answer this question, skin from fetal Sprague-Dawley rats (N = 56) at time points that represented both the scarless and scar-forming periods of rat gestation was harvested. In addition, fibroblasts derived from fetal rat skin were cultured in vitro at similar times. These cells were expanded in culture and, when confluent, total ribonucleic acid from both fibroblasts and whole skin was extracted and subjected to Northern blot analysis with probes for EGF and PDGF-B. Results demonstrated that neither EGF nor PDGF-B gene expression changed markedly as a function of gestational age in fetal fibroblasts alone. In whole skin, however, both EGF and PDGF-B demonstrated a marked decrease in gene expression with increasing gestational age. Furthermore, the most striking decrease in gene expression for both cytokines came between 16 and 18 days of gestation-the transition point between scarless and scar-forming repair in the fetal rat. These data suggest that EGF and PDGF may play a role in the mechanism of scarless cutaneous repair. Moreover, it appears that fetal fibroblasts are not the cell type responsible for this differential gene expression. These results raise questions about the unique cytokine milieu likely to be present during the time of scarless healing and the cells that ultimately guide the mechanisms leading to skin regeneration.

    View details for Web of Science ID 000171407400010

    View details for PubMedID 11601578

  • Flexor tendon wound healing in vitro: the effect of lactate on tendon cell proliferation and collagen production. journal of hand surgery Klein, M. B., Pham, H., Yalamanchi, N., Chang, J. 2001; 26 (5): 847-854

    Abstract

    Flexor tendon repair in zone II is complicated by adhesions to the surrounding fibro-osseous sheath. Lactate is an early mediator of wound healing known to play an important role in stimulation of collagen production after cellular injury. Little attention has been paid to the role of lactate in flexor tendon wound healing. In this study tendon and tendon sheath were excised from rabbit forepaws. We examined proliferation of tendon sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes; collagen production by each of these 3 cell types; and effects of lactate on cell proliferation and collagen production. Three cell lines, tendon sheath, epitenon, and endotenon, were isolated and cultured. Tendon sheath fibroblasts showed the greatest proliferation. All 3 cell lines produced collagen I, II, and III. Lactate significantly increased collagen production by all 3 cell lines. We show that cells of the tendon sheath, epitenon, and endotenon produce collagen in vitro. Modulation of lactate levels may provide a means to modulate collagen production.

    View details for PubMedID 11561237

  • Acute nerve grafting in traumatic injuries PROCEEDINGS OF THE INAUGURAL CONGRESS OF THE WORLD SOCIETY FOR RECONSTRUCTIVE MICROSURGERY Sud, V., Chang, J., Lineaweaver, W. C. 2001: 523-525
  • Free flap closure in complex congenital and acquired defects of the palate ANNALS OF PLASTIC SURGERY Turk, A. E., Chang, J., Soroudi, A. E., Hui, K., Lineaweaver, W. C. 2000; 45 (3): 274-279

    Abstract

    Extensive palatal defects cause substantial morbidity, including nasal regurgitation, poor oral hygiene, loose-fitting obturators, and difficulty with speech. Microvascular techniques allow the surgeon to repair these complex defects with a one-stage reconstruction, in contrast to possible multistage local or regional flap reconstruction. In this retrospective review, the authors present their 5-year experience with free flap coverage of extensive palatal defects. From 1993 to 1998, 6 patients underwent free flap coverage of large palatal defects. The etiology of the large palatal defects included trauma (N = 1), neoplasm (N = 4), and a recurrent congenital cleft palatal fistula (N = 1). Three patients underwent osteocutaneous radial forearm flaps and 1 patient underwent a fasciocutaneous radial forearm flap. The remaining 2 patients underwent rectus abdominis muscle flaps. The ipsilateral facial artery and vein were used as the recipient vessels in all patients. There were no intraoperative complications (surgical or anesthetic). Postoperatively, 2 patients had surgical evacuation of small flap hematomas. One patient underwent revision of the fasciocutaneous flap. All flaps survived. In our experience, the benefits of free flap reconstruction of complex palatal fistulas seem to outweigh the risks of the operation, with reliable long-term results.

    View details for Web of Science ID 000089178200009

    View details for PubMedID 10987529

  • Management of hand and upper-extremity infections in heart transplant recipients PLASTIC AND RECONSTRUCTIVE SURGERY Klein, M. B., Chang, J. 2000; 106 (3): 598-601

    Abstract

    Hand and upper-extremity infections are routinely managed by antibiotics, immobilization, and limited incision and drainage. However, in immunocompromised patients, these infections may be more aggressive and they may require more emergent treatment. The authors performed a retrospective review of the Stanford University Medical Center experience with hand and upper-extremity infections in 911 cardiac transplant recipients over the past 30 years. Thirteen heart transplant recipients were treated for infections of the hand and upper extremity on an inpatient basis. Ten patients (77 percent) required operative debridement, and three (23 percent) required more than one operative procedure. Nine patients (69 percent) had bacterial infections, six (46 percent) had fungal infections [four of these patients (31 percent) had both bacterial and fungal infections], one (7.7 percent) had a mycobacterial infection, and one (7.7 percent) was not cultured. Hand and upper-extremity infections in transplant recipients frequently resulted in deep-space infections, tenosynovitis, and osteomyelitis. The authors believe such infections represent a surgical emergency, requiring immediate evaluation by hand surgeons and early, aggressive treatment.

    View details for Web of Science ID 000088925700011

    View details for PubMedID 10987466

  • Community acquired methicillin-resistant Staphylococcus aureus hand infections: case reports and clinical implications. journal of hand surgery Karanas, Y. L., Bogdan, M. A., Chang, J. 2000; 25 (4): 760-763

    Abstract

    We report a series of 4 cases of community acquired methicillin-resistant Staphylococcus aureus hand infections in patients without risk factors. Methicillin-resistant S aureus infections commonly involve the skin and soft tissue; therefore, hand infections may become more common as the prevalence of this pathogen increases. Hand surgeons must be aware of this emerging pathogen and obtain appropriate tissue cultures to diagnose and effectively treat this infection.

    View details for PubMedID 10913220

  • Proliferative hemangiomas: Analysis of cytokine gene expression and angiogenesis PLASTIC AND RECONSTRUCTIVE SURGERY Chang, J., Most, D., Bresnick, S., Mehrara, B., Steinbrech, D. S., Reinisch, J., Longaker, M. T., Turk, A. E. 1999; 103 (1): 1-9

    Abstract

    Hemangiomas are benign vascular tumors of childhood that can lead to disfigurement and/or life-threatening consequences. The pathogenesis of hemangioma formation is likely to involve increased angiogenesis. Basic fibroblast growth factor and vascular endothelial growth factor are cytokines that stimulate angiogenesis in multiple in vivo and in vitro models. Proliferative hemangiomas have been found to have elevated levels of basic fibroblast growth factor and vascular endothelial growth factor protein, but the gene expression of these cytokines in human specimens has not been previously studied. We examined the gene expression and spatial distribution of basic fibroblast growth factor and vascular endothelial growth factor messenger RNA in proliferative versus involuted human hemangioma specimens using nonisotopic in situ hybridization techniques. Thirteen hemangioma specimens were harvested during initial surgical excision. In situ hybridization was performed on frozen sections of both proliferative and involuted hemangioma specimens using genetically engineered antisense probes specific for basic fibroblast growth factor and vascular endothelial growth factor messenger RNA. Controls were an interleukin-6 sense sequence and a transforming growth factor-beta 1 antisense sequence. A large number of cells within the specimens of proliferative hemangiomas revealed localized gene expression of basic fibroblast growth factor and vascular endothelial growth factor messenger RNA (626 +/- 129 and 1660 +/- 371 cells/mm2, respectively). The majority of the cells were endothelial in origin. In contrast, involuted hemangioma specimens revealed significantly lower numbers of cells staining positive for basic fibroblast growth factor and vascular endothelial growth factor messenger RNA (44 +/- 11 and 431 +/- 76 cells/mm2, respectively; p < 0.05). Transforming growth factor-beta 1 messenger RNA was slightly more expressed by involuted hemangiomas (117 +/- 30 cells/mm2). There were very low levels of transforming growth factor-beta 1 gene expression from proliferative hemangiomas (37 +/- 24 cells/mm2; p < 0.02). These data demonstrate that (1) in situ hybridization allows identification and relative quantitation of cells expressing messenger RNA for specific growth factors in human hemangioma specimens; (2) basic fibroblast growth factor and vascular endothelial growth factor messenger RNA are up-regulated in proliferative hemangiomas; and (3) transforming growth factor-beta 1 messenger RNA remains low in both proliferative and involuted hemangiomas. Because basic fibroblast growth factor and vascular endothelial growth factor messenger RNA have been implicated in the pathobiology of human hemangioma formation, biochemical modulation of these angiogenic cytokines may eventually help inhibit proliferation and promote regression of hemangiomas.

    View details for Web of Science ID 000077707200001

    View details for PubMedID 9915157

  • Molecular studies in flexor tendon wound healing: The role of basic fibroblast growth factor gene expression JOURNAL OF HAND SURGERY-AMERICAN VOLUME Chang, J., Most, D., Thunder, R., Mehrara, B., Longaker, M. T., Lineaweaver, W. C. 1998; 23A (6): 1052-1058

    Abstract

    Basic fibroblast growth factor (bFGF) is a cytokine that plays a fundamental role in angiogenesis. This study examines bFGF messenger RNA (mRNA) expression in a rabbit flexor tendon wound healing model. Thirty-four New Zealand white rabbit forepaws underwent transection and repair of the middle digit flexor digitorum profundus tendon in zone II. Tendons were harvested at increasing time intervals and analyzed by in situ hybridization and immunohistochemistry. Few tenocytes and tendon sheath cells expressed bFGF mRNA in unwounded tendons. In contrast, tendons subjected to transection and repair exhibited an increased signal for bFGF mRNA in both resident tenocytes concentrated along the epitenon and infiltrating fibroblasts and inflammatory cells from the tendon sheath. These data demonstrate that (1) normal tenocytes and tendon sheath cells are capable of bFGF production, (2) bFGF mRNA is upregulated in the tendon wound environment, and (3) the upregulation of this angiogenic cytokine occurs in tenocytes as well as in tendon sheath fibroblasts and inflammatory cells.

    View details for Web of Science ID 000077120700015

  • A Method for Immobilizing the Forelimbs of Rabbits. Contemporary topics in laboratory animal science / American Association for Laboratory Animal Science Thunder, R. M., Chang, J., Broome, R. L., Most, D. 1998; 37 (5): 94-95

    Abstract

    Immobilizing the forelimbs of rabbits after surgical procedures is necessary to allow healing, yet it often can be difficult, because rabbits are often able to pull the repaired limb from its cast soon after surgery and well before adequate tissue repair has taken place. We describe here a method of immobilization that uses 3 layers of cast material combined with flexion of the radiocarpal and radiohumeral joints. This method resulted in successful immobilization in 97% of the rabbits on which it was used.

    View details for PubMedID 12456142

  • Tibialis anterior turnover flap coverage of exposed tibia in a severely burned patient BURNS Chang, J., Most, D., HOVEY, L. M., Yim, K. K. 1997; 23 (1): 69-71

    Abstract

    A case report of a longitudinally split tibialis anterior turnover flap reconstruction of an exposed tibia in a burn patient is presented here. The patient had sustained deep partial- and full-thickness burns to 70 per cent of his total body surface area (TBSA), resulting in an exposed left patella and upper two-thirds of the left tibia. Although full thickness loss of skin occurred on the left lower leg, no muscle trauma was sustained. Reconstruction was therefore deemed possible using local muscle tissue to provide transposed flap coverage. A gastrocnemius muscle flap was used to cover the exposed patella and superior aspect of the tibia. A portion of the tibialis anterior muscle was split longitudinally and turned over medially to cover the remaining exposed tibia. The advantages offered by this infrequently used flap include technical simplicity, reliability, minimal donor site dysfunction and the allowance of future use of the soleus flap. The tibialis anterior turnover flap may therefore have wide applicability for reconstruction of the severely burned lower extremity.

    View details for Web of Science ID A1997WE79000015

    View details for PubMedID 9115615

  • The role of bFGF and VEGF gene expression in proliferative hemangiomas CRANIOFACIAL SURGERY 7 Chang, J., Most, D., Bresnick, S., Reinisch, J., Longaker, M. T., Turk, A. 1997: 303-304

Conference Proceedings


  • Differential expression of transforming growth factor-beta receptors in a rabbit zone II flexor tendon wound healing model Ngo, M., Pham, H., Longaker, M. T., Chang, J. LIPPINCOTT WILLIAMS & WILKINS. 2001: 1260-1267

    Abstract

    Flexor tendon repair in zone II is complicated by adhesions that impair normal postoperative gliding. Transforming growth factor-beta (TGF-beta) is a family of growth factors that has been implicated in scar formation. The TGF-beta family of proteins binds to three distinct classes of membrane receptors, termed RI, RII, and RIII. In this study, we analyzed the temporal and spatial distribution of TGF-beta receptor isoforms (RI, RII, and RIII) in a rabbit zone II flexor tendon wound healing model.Twenty-eight adult New Zealand White rabbit forepaws underwent isolation of the middle digit flexor digitorum profundus tendon in zone II. The tendons underwent transection in zone II and immediate repair. The tendons were harvested at increasing time points: 1, 3, 7, 14, 28, and 56 days postoperatively (n = 4 at each time point). The control flexor tendons were harvested without transection and repair (n = 4). Immunohistochemical analysis was used to detect the expression patterns for TGF-beta receptors RI, RII, and RIII. Immunohistochemical staining of the transected and repaired tendons demonstrated up-regulation of TGF-beta RI, RII, and RIII protein levels. TGF-beta receptor production in the experimental group (transection and repair) was concentrated in the epitenon and along the repair site. Furthermore, the TGF-beta receptor expression levels peaked at day 14 and decreased by day 56 postoperatively. In contrast, minimal receptor expression was observed in the untransected and unrepaired control tendons. These data provide evidence that (1) TGF-beta receptors are up-regulated after injury and repair; (2) peak levels of TGF-beta receptor expression occurred at day 14 and decreased by day 56 after wounding and repair; and (3) both the tendon sheath and epitenon have the highest receptor expression, and both may play critical roles in flexor tendon wound healing. Understanding the up-regulation of TGF-beta isoforms and the up-regulation of their corresponding receptors during flexor tendon wound healing provides new targets for biomolecular modulation of postoperative scar formation.

    View details for Web of Science ID 000171428900025

    View details for PubMedID 11604629

  • Staged closure of complicated bronchopleural fistulas Turk, A. E., Karanas, Y. L., Cannon, W., Chang, J. LIPPINCOTT WILLIAMS & WILKINS. 2000: 560-564

    Abstract

    Bronchopleural fistulas remain a major complication after thoracic surgery. Despite continued advances in the treatment of this difficult problem, perioperative mortality remains as high as 15%. Multiple treatment strategies have been described with varying degrees of success. Successful treatment of chronic bronchopleural fistulas requires aggressive control of infection, adequate drainage of the chest cavity, closure of the fistula with vascularized tissue, and obliteration of the chest cavity. The authors present their experience with 3 patients who underwent a two-stage closure of their bronchopleural fistulas with pectoralis major muscle flaps followed by omental flap obliteration of the chest cavity. Each patient had previously undergone an Eloesser procedure for chest cavity drainage. The initial muscle flap operation is a small procedure that can be done rapidly with minimal morbidity in chronically ill patients. The intervening period between procedures allows patients to continue aggressive nutritional and physical rehabilitation until they are able to tolerate a second operation for chest cavity obliteration. All bronchopleural fistulas in our series healed, with one minor complication. A staged closure is a safe and effective alternative treatment for chronic and recurrent bronchopleural fistulas.

    View details for Web of Science ID 000165235900019

    View details for PubMedID 11092371

  • Plastic surgeons in American hand surgery: The past, present, and future Chang, J., Hentz, V. R., Chase, R. A. LIPPINCOTT WILLIAMS & WILKINS. 2000: 406-412

    View details for Web of Science ID 000088631000025

    View details for PubMedID 10946941

  • A single surgeon's experience with the Delaire palatoplasty Schendel, S. A., Lorenz, H. P., Dagenais, D., Hopkins, E., Chang, J. LIPPINCOTT WILLIAMS & WILKINS. 1999: 1993-1997

    Abstract

    The purpose of this review was to evaluate the clinical outcomes regarding velopharyngeal insufficiency and fistulization in patients with cleft palate who underwent primary repair with the one-stage Delaire palatoplasty. All patients who had a primary Delaire-type palatoplasty performed by the senior surgeon over a 10-year period (1988 to 1998) were studied. During this period, each consecutive patient with an open palatal cleft underwent the same type of repair by the same surgeon. Speech quality and velopharyngeal competence as determined by a single speech pathologist were recorded. A total of 95 patients were included in this series. The average length of follow-up was 31 months (range, 1 to 118 months). Average age at time of surgery was 13.3 months (range, 6 to 180 months). Thirty-one patients (32.6 percent) had significant associated anomalies. The average length of hospital stay was 1.9 days (range, 1 to 8 days) with a trend in recent years toward discharge on postoperative day 1. There were no intraoperative complications, either surgical or anesthetic. Three patients (3.2 percent) developed palatal fistula; none of them required repair. Six patients (6.3 percent) had velopharyngeal incompetence. In patients with more than 1 year of follow-up, the incidence of velopharyngeal incompetence was 9.2 percent (6 of 65). The incidence of fistula after the Delaire palatoplasty was lower than usually reported. The incidence of velopharyngeal incompetence requiring pharyngoplasty was equal to or lower than that seen after other types of palatoplasty, suggesting superior soft-palate muscle function attributable to approximation of the musculus uvulae. The Delaire palatoplasty results in a functional palate with low risk for fistula formation and velopharyngeal incompetence.

    View details for Web of Science ID 000083854900009

    View details for PubMedID 11149761

  • Gene expression of transforming growth factor beta-1 in rabbit zone II flexor tendon wound healing: Evidence for dual mechanisms of repair Chang, J., Most, D., Stelnicki, E., Siebert, J. W., Longaker, M. T., Hui, K., Lineaweaver, W. C. LIPPINCOTT WILLIAMS & WILKINS. 1997: 937-944

    Abstract

    The postoperative outcome of hand flexor tendon repair can be complicated by adhesions between the repair site and surrounding tissue. To date, the biology of hand flexor tendon wound healing remains controversial--both intrinsic (resident tenocyte) and extrinsic (tendon sheath fibroblast and inflammatory cell) processes may contribute to repair. Transforming growth factor beta-1 is a cytokine that plays multiple roles in wound healing but is also implicated in the pathogenesis of excessive scar formation. This study examines the activation of transforming growth factor beta-1 mRNA in a rabbit zone II flexor tendon wound-healing model. Forty New Zealand White rabbit forepaws underwent complete transection and repair of the middle digit flexor digitorum profundus tendon in zone II. Tendons were harvested at increasing time intervals (1, 3, 7, 14, 28, and 56 days) and analyzed by in situ hybridization and immunohistochemistry to determine the expression patterns of transforming growth factor beta-1. A small number of tenocytes exhibited expression of transforming growth factor beta-1 mRNA at baseline in nonwounded control tendon specimens. The surrounding tendon sheath in these control specimens also revealed low numbers of fibroblasts and inflammatory cells expressing transforming growth factor beta-1 mRNA. In contrast, flexor tendons subjected to transection and repair exhibited increased signal for transforming growth factor beta-1 mRNA in both resident tenocytes and infiltrating fibroblasts and inflammatory cells from the tendon sheath. These data demonstrate that (1) normal unwounded tenocytes and tendon sheath cells are capable of transforming growth factor beta-1 production, (2) this cytokine is activated in the tendon wound environment, as evidenced by mRNA upregulation, and (3) the upregulation of this cytokine in both "intrinsic" tenocytes and "extrinsic" tendon sheath fibroblasts and inflammatory cells supports dual mechanisms for tendon repair. Because transforming growth factor beta-1 is thought to contribute to the pathogenesis of excessive scar formation, the findings presented here suggest that perioperative biochemical modulation of transforming growth factor beta-1 levels may help limit flexor tendon adhesion formation.

    View details for Web of Science ID A1997XW23900016

    View details for PubMedID 9290662

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