Adhesions in a murine flexor tendon graft model: Autograft versus allograft reconstruction

Reconstruction of flexor tendons often results in adhesions that compromise joint flexion. Little is known about the factors involved in the formation of flexor tendon graft adhesions. In this study, we developed and characterized a novel mouse model of flexor digitorum longus (FDL) tendon reconstruction with live autografts or reconstituted freeze‐dried allografts. Grafted tendons were evaluated at multiple time points up to 84 days post‐reconstruction. To assess the flexion range of the metatarsophalangeal joint, we developed a quantitative outcome measure proportional to the resistance to tendon gliding due to adhesions, which we termed the Gliding Coefficient. At 14 days post‐grafting, the Gliding Coefficient was 29‐ and 26‐fold greater than normal FDL tendon for both autografts and allografts, respectively (p < 0.001), and subsequently doubled for 28‐day autografts. Interestingly, there were no significant differences in maximum tensile force or stiffness between live autograft and freeze‐dried allograft repairs over time. Histologically, autograft healing was characterized by extensive remodeling and exuberant scarring around both the ends and the body of the graft, whereas allograft scarring was abundant only near the graft–host junctions. Gene expression of GDF‐5 and VEGF were significantly increased in 28‐day autografts compared to allografts and to normal tendons. These results suggest that the biomechanical advantages for tendon reconstruction using live autografts over devitalized allografts are minimal. This mouse model can be useful in elucidating the molecular mechanisms in tendon repair and can aid in preliminary screening of molecular treatments of flexor tendon adhesions. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:824–833, 2008

[1]  G. Balian,et al.  Growth and differentiation factor-5 (GDF-5) stimulates osteogenic differentiation and increases vascular endothelial growth factor (VEGF) levels in fat-derived stromal cells in vitro. , 2007, Bone.

[2]  D. Hart,et al.  Patterns of mRNA expression for matrix molecules and growth factors in flexor tendon injury: differences in the regulation between tendon and tendon sheath. , 2006, The Journal of hand surgery.

[3]  T. Messer,et al.  Complications After Treatment of Flexor Tendon Injuries , 2006, The Journal of the American Academy of Orthopaedic Surgeons.

[4]  A. Curtis,et al.  Neutralisation of TGF beta or binding of VLA-4 to fibronectin prevents rat tendon adhesion following transection. , 2005, Cytokine.

[5]  M. Boyer Flexor tendon biology. , 2005, Hand clinics.

[6]  Hiromu Ito,et al.  Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy , 2005, Nature Medicine.

[7]  A. Sharma,et al.  Acellular and glutaraldehyde-preserved tendon allografts for reconstruction of superficial digital flexor tendon in bovines: Part II--Gross, microscopic and scanning electron microscopic observations. , 2003, Journal of veterinary medicine. A, Physiology, pathology, clinical medicine.

[8]  A. Sharma,et al.  Acellular and glutaraldehyde-preserved tendon allografts for reconstruction of superficial digital flexor tendon in bovines: Part I--Clinical, radiological and angiographical observations. , 2003, Journal of veterinary medicine. A, Physiology, pathology, clinical medicine.

[9]  R. Gelberman,et al.  Quantitative variation in vascular endothelial growth factor mRNA expression during early flexor tendon healing: an investigation in a canine model , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[10]  E. Hunziker,et al.  GDF‐5 deficiency in mice alters the ultrastructure, mechanical properties and composition of the Achilles tendon , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[11]  R. Gelberman,et al.  Expression of mRNA for vascular endothelial growth factor at the repair site of healing canine flexor tendon , 2000, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[12]  M. Longaker,et al.  Studies in Flexor Tendon Wound Healing: Neutralizing Antibody to TGF‐&bgr;1 Increases Postoperative Range of Motion , 2000, Plastic and reconstructive surgery.

[13]  R. Ganz,et al.  Periacetabular osteotomy in the treatment of neurogenic acetabular dysplasia. , 1999, The Journal of bone and joint surgery. British volume.

[14]  Matthew J. Silva,et al.  Effects of increased in vivo excursion on digital range of motion and tendon strength following flexor tendon repair , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[15]  R. Gelberman,et al.  The effect of gap formation at the repair site on the strength and excursion of intrasynovial flexor tendons. An experimental study on the early stages of tendon-healing in dogs. , 1999, The Journal of bone and joint surgery. American volume.

[16]  J. Taras,et al.  Treatment of flexor tendon injuries: surgeons' perspective. , 1999, Journal of hand therapy : official journal of the American Society of Hand Therapists.

[17]  P. Aspenberg,et al.  Enhanced tendon healing with GDF 5 and 6. , 1999, Acta orthopaedica Scandinavica.

[18]  M. Longaker,et al.  Molecular studies in flexor tendon wound healing: the role of basic fibroblast growth factor gene expression. , 1998, The Journal of hand surgery.

[19]  S. Woo,et al.  The Marshall R. Urist Young Investigator Award , 1997 .

[20]  S. Woo,et al.  Autogenous flexor tendon grafts: Biologic mechanisms for incorporation , 1997 .

[21]  M. Longaker,et al.  Gene Expression of Transforming Growth Factor Beta‐1 in Rabbit Zone II Flexor Tendon Wound Healing: Evidence for Dual Mechanisms of Repair , 1997, Plastic and reconstructive surgery.

[22]  R. Gelberman,et al.  Autogenous flexor tendon grafts: Fibroblast activity and matrix remodeling in dogs , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  J. Bechtold,et al.  The Effects of Freeze-drying and Ethylene Oxide Sterilization on the Mechanical Properties of Human Patellar Tendon , 1994, The American journal of sports medicine.

[24]  E. May,et al.  Gap formation after flexor tendon repair in zone II. Results with a new controlled motion programme. , 1993, Scandinavian journal of plastic and reconstructive surgery and hand surgery.

[25]  E. May,et al.  Tendon excursions after flexor tendon repair in zone. II: Results with a new controlled-motion program. , 1993, The Journal of hand surgery.

[26]  D. Drez,et al.  Anterior cruciate ligament reconstruction using freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts , 1991, The American journal of sports medicine.

[27]  D. W. Jackson,et al.  Intraarticular reaction associated with the use of freeze-dried, ethylene oxide-sterilized bone-patella tendon-bone allografts in the reconstruction of the anterior cruciate ligament , 1990, The American journal of sports medicine.

[28]  D. R. Anderson,et al.  Bridge flexor tendon grafts. , 1989, Clinical orthopaedics and related research.

[29]  S. Dovelle,et al.  Early controlled motion following flexor tendon graft. , 1988, The American journal of occupational therapy : official publication of the American Occupational Therapy Association.

[30]  R. Nasca The use of freeze-dried allografts in the management of global rotator cuff tears. , 1988, Clinical orthopaedics and related research.

[31]  R. Gelberman,et al.  Factors influencing flexor tendon adhesions. , 1985, Hand clinics.

[32]  T. K. Liu,et al.  Clinical use of refrigerated flexor tendon allografts to replace a silicone rubber rod. , 1983, The Journal of hand surgery.

[33]  D. A. Webster,et al.  Mechanical and functional properties of implanted freeze-dried flexor tendons. , 1983, Clinical orthopaedics and related research.

[34]  C. W. Chan,et al.  The Healing of Freeze-Dried Rabbit Flexor Tendon in a Synovial Fluid Environment , 1983, The Hand.

[35]  Austin D. Potenza,et al.  The synovial cavity as a "tissue culture in situ"--science or nonsense? , 1982, The Journal of hand surgery.

[36]  M. Shaw The injured hand. , 1961, The Transactions of the Association of Industrial Medical Officers.

[37]  S. Bunnell The injured hand; principles of treatment. , 1953, Industrial medicine & surgery.

[38]  G. Bentley,et al.  Modulation of the formation of adhesions during the healing of injured tendons. , 2000, The Journal of bone and joint surgery. British volume.

[39]  D. Amiel,et al.  Intercalary flexor tendon grafts. A morphological study of intrasynovial and extrasynovial donor tendons. , 1992, Scandinavian journal of plastic and reconstructive surgery and hand surgery.

[40]  G. Poehling,et al.  Arthroscopic reconstruction of the anterior cruciate ligament using allograft tendon. , 1988, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[41]  W. T. Green,et al.  Freeze-Dried Fascia Lata Allografts: A Review of 47 Cases , 1981, Journal of pediatric orthopedics.