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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR044391-16
Application #
8443431
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Wang, Fei
Project Start
1998-01-01
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2015-01-31
Support Year
16
Fiscal Year
2013
Total Cost
$459,525
Indirect Cost
$155,405
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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
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
Amadio, Peter C (2013) Gliding resistance and modifications of gliding surface of tendon: clinical perspectives. Hand Clin 29:159-66
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
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
Zhao, Chunfeng; Ettema, Anke M; Berglund, Lawrence J et al. (2011) Gliding resistance of flexor tendon associated with carpal tunnel pressure: a biomechanical cadaver study. J Orthop Res 29:58-61
Yoshii, Yuichi; Zhao, Chunfeng; Henderson, Jacqueline et al. (2011) Velocity-dependent changes in the relative motion of the subsynovial connective tissue in the human carpal tunnel. J Orthop Res 29:62-6
van Doesburg, Margriet H M; Yoshii, Yuichi; Villarraga, Hector R et al. (2010) Median nerve deformation and displacement in the carpal tunnel during index finger and thumb motion. J Orthop Res 28:1387-90
Zhao, Chunfeng; Sun, Yu-Long; Kirk, Ramona L et al. (2010) Effects of a lubricin-containing compound on the results of flexor tendon repair in a canine model in vivo. J Bone Joint Surg Am 92:1453-61

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