The overall goal of this project is to improve the results of treatment for tendon injury through a better understanding of, and the development of therapies that affect the tendon gliding surface. The underlying hypothesis continues to be that improvements in the results of flexor tendon repair can be obtained by methods that minimize friction of the gliding surfaces of tendon and sheath. Changes in suture methods and postoperative therapy regimens have improved the results of tendon repair and rehabilitation, but adhesions still occur. We therefore plan to study methods to further improve gliding and reduce adhesions by physicochemical and pharmacological modification of the tendon gliding surface, and the effect of these modifications on tendon healing, tendon gliding, and the expression of natural lubricants on the tendon surface, principally hyaluronan and lubricin.
Our Specific Aims are, first, to investigate the effect of physicochemical attachment of hyaluronan and lubricin to the tendon surface on tendon gliding in canine and human tendons in vitro; second, to investigate the effects of physicochemical attachment of lubricants to the tendon gliding surface on tendon healing and tendon gliding in a canine model in vivo; and, third, to investigate the effects of pharmacological tendon surface modification with topical 5 fluorouracil on tendon healing, tendon gliding, and the expression of tendon surface lubricants in a canine model in vivo. The specific hypotheses that will be tested are, respectively, that physicochemical attachment of lubricants to the tendon surface will enhance tendon gliding ability in vitro; that physicochemical attachment of lubricants to the healing tendon surface will enhance tendon gliding ability, reduce adhesions, and not adversely affect tendon healing; and that pharmacologic treatment of the healing tendon surface will be associated with an increase in surface lubricants and a reduction in gliding resistance, without adversely affecting tendon healing. Based on the results of the work proposed here, we anticipate future studies, which might directly manipulate the expression of these surface lubricants, with the ultimate aim of producing adhesion-free tendon gliding and a soundly healed tendon after tendon injury and repair.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR044391-11
Application #
7379997
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Wang, Fei
Project Start
1998-01-01
Project End
2009-01-31
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
11
Fiscal Year
2008
Total Cost
$383,757
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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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