The overall goal of this project is to improve the results of tendon repair through the development of therapies that affect the tendon gliding surface. In the first two funding periods we showed that surgeons could reduce adhesions after tendon repair by changes in suture methods and postoperative therapy regimens. These changes have been incorporated into clinical practice in our own and other centers. In the third funding period, we explored means to further improve tendon gliding and reduce adhesions by physicochemical and pharmacological means. These studies have shown that adhesions can be dramatically reduced with an engineered tendon surface coating containing lubricin, a lubricating glycoprotein ubiquitous in articular cartilage, but in some cases the healing process in lubricin treated tendons is delayed. In this funding period, therefore, we propose to investigate methods to preserve the beneficial effects of lubricin while improving intrinsic tendon healing through a tissue engineering approach. We have recently developed an interpositional collagen patch seeded with bone marrow-derived stromal cells (BMSC) that appears to accelerate tendon healing in vitro. Our central hypothesis is that this BMSC seeded patch will improve the speed and strength of tendon healing in vivo, without adversely affecting the beneficial effects of lubricin-augmented repair and rehabilitation on tendon gliding and adhesions. To test this hypothesis we have developed three aims.
Aim 1 is to investigate the healing of flexor tendons following the incorporation of BMSC seeded, cytokine augmented collagen patch into the repair site in a canine model in vitro.
Aim 2 is to investigate the effects a BMSC tendon patch combined with surface modification on flexor tendon repair in a canine model in vivo.
Aim 3 is to investigate the effect of surface modification and a BMSC patch on animals subjected to a postponed tendon rehabilitation protocol. If these aims are achieved, we believe that this two-pronged tissue engineering approach could be developed into a clinical method to provide sound, adhesion free tendon repairs. In addition, such an approach could provide benefits in reducing adhesions in clinical situations where immediate rehabilitation with early motion is impossible, such as in cases of replantation or other complex trauma, as well as in young children or other uncooperative patients.

Public Health Relevance

Tendon injuries are common and often devastating, resulting in permanent loss of motion. The principal problem is excessive scarring, resulting in adhesions that limit tendon gliding. This project aims to reduce or eliminate adhesions through a combination of mechanical, physiochemical and biological means, fundamentally re-engineering the injured tendon and its interface with the surrounding tissues.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Wang, Fei
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Mayo Clinic, Rochester
United States
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Zhao, Chunfeng; Ozasa, Yasuhiro; Shimura, Haruhiko et al. (2016) Effects of lubricant and autologous bone marrow stromal cell augmentation on immobilized flexor tendon repairs. J Orthop Res 34:154-60
Ozasa, Y; Gingery, A; Amadio, P C (2015) Muscle-derived stem cell seeded fibrin gel interposition produces greater tendon strength and stiffness than collagen gel in vitro. J Hand Surg Eur Vol 40:747-9
Zhao, Chunfeng; Ozasa, Yasuhiro; Reisdorf, Ramona L et al. (2014) CORRĀ® ORS Richard A. Brand Award for Outstanding Orthopaedic Research: Engineering flexor tendon repair with lubricant, cells, and cytokines in a canine model. Clin Orthop Relat Res 472:2569-78
Ozasa, Yasuhiro; Gingery, Anne; Thoreson, Andrew R et al. (2014) A comparative study of the effects of growth and differentiation factor 5 on muscle-derived stem cells and bone marrow stromal cells in an in vitro tendon healing model. J Hand Surg Am 39:1706-13
Zhao, Chunfeng; Wei, Zhuang; Reisdorf, Ramona L et al. (2014) The effects of biological lubricating molecules on flexor tendon reconstruction in a canine allograft model in vivo. Plast Reconstr Surg 133:628e-637e
Vanhees, Matthias; Thoreson, Andrew R; Larson, Dirk R et al. (2013) The effect of suture preloading on the force to failure and gap formation after flexor tendon repair. J Hand Surg Am 38:56-61
Sun, Yu-Long; Zhao, Chunfeng; Jay, Gregory D et al. (2013) Effects of stress deprivation on lubricin synthesis and gliding of flexor tendons in a canine model in vivo. J Bone Joint Surg Am 95:273-8
Amadio, Peter C (2013) Gliding resistance and modifications of gliding surface of tendon: clinical perspectives. Hand Clin 29:159-66
Moriya, T; Larson, M C; Zhao, C et al. (2012) The effect of core suture flexor tendon repair techniques on gliding resistance during static cycle motion and load to failure: a human cadaver study. J Hand Surg Eur Vol 37:316-22
Hayashi, Masanori; Zhao, Chunfeng; An, Kai-Nan et al. (2012) Cell migration after synovium graft interposition at tendon repair site. Hand (N Y) 7:374-9

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