Flexor tendon injury is a common and disabling clinical problem. If the damaged tendon cannot be immediately and directly repaired or primary repairs fail, a tendon graft is indicated. However, clinical outcomes have demonstrated high rates of complications after tendon graft, with adhesion formation and poor digit function. Clinical and animal models have shown that intrasynovial autografts provide better results than extrasynovial autografts, but clinical sources of intrasynovial tendons for use as tendon autografts are limited. Although our previous work has shown that an engineered extrasynovial graft surface, modified with carbodiimide derivatized HA (cd-HA), results in improved tendon gliding and decreased postoperative adhesions, resulting digit function still falls far short of normal. While allograft sources using intrasynovial tendon are possible, procedures used for allograft preparation and preservation damage the tendon surface and decrease its gliding ability. Encouragingly, our recent pilot studies have shown that surface treatment with cd-HA improved intrasynovial allograft frictional properties and decreased adhesion formation. More encouragingly, these improvements were noted even when the treated allografts were used in a scarred tendon bed, a much more clinically relevant model than the usual animal model used to study flexor tendon reconstruction, i.e., a normal, previously unoperated digit. More recently, we have developed a new compound for tendon surface modification by adding lubricin, a mucinous glycoprotein, to the cd-HA (cd-HA-lubricin). Our preliminary studies in vitro have shown that cd-HA-lubricin further improves the lubrication of extrasynovial tendon to a level comparable to intrasynovial tendon. Our overall goal is to develop a clinically applicable tendon graft alternative, an engineered allograft with a surface lubricated with cd-HA-lubricin that could become an off-the-shelf, functionally superior alternative to conventional tendon grafting. Given the known anti-adhesive properties of lubricin, we hypothesize that outcomes better than conventional extrasynovial autografting can be achieved with cd-HA-lubricin treated allografts in vivo. If our goals are achieved and the cd-HA-lubricin modified graft provides superior outcomes, clinical translation studies will be proposed in the future. We will also be able to use our novel engineered surface modification to study other applications of tendon grafting where adhesion prevention is important, such as for the rotator cuff.

Public Health Relevance

The restoration of normal hand function is crucial after flexor tendon injuries, and tendon reconstruction plays an important role to achieve this goal. Unfortunately, poor tendon reconstruction results have challenged hand surgeons for over a half century. This research proposal is to develop a novel method for engineering tendon surfaces to improve the outcomes of tendon reconstruction leading towards restoration of normal hand function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR057745-04
Application #
8452726
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2010-04-07
Project End
2014-08-31
Budget Start
2013-04-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$310,057
Indirect Cost
$104,857
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Qin, Ting-Wu; Sun, Yu-Long; Thoreson, Andrew R et al. (2015) Effect of mechanical stimulation on bone marrow stromal cell-seeded tendon slice constructs: a potential engineered tendon patch for rotator cuff repair. Biomaterials 51:43-50
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Ji, Xiaoxi; Bao, Nirong; An, Kai-Nan et al. (2015) A Canine Non-Weight-Bearing Model with Radial Neurectomy for Rotator Cuff Repair. PLoS One 10:e0130576
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Thoreson, Andrew R; Hiwatari, Ryo; An, Kai-Nan et al. (2015) The Effect of 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide Suture Coating on Tendon Repair Strength and Cell Viability in a Canine Model. J Hand Surg Am 40:1986-91
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

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