FLEXOR TENDON HEALING

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DESCRIPTION (provided by applicant): One-third of all acute injuries in workers are to the upper extremity, a large percentage of which are open wounds requiring extensive tendon surgery. Experimental and clinical studies have reported a high incidence of repair site elongation and adhesion formation following primary tendon and tendon to bone suture, with repair site failure occurring most frequently in the first three weeks following repair. Recent studies have demonstrated that an alteration of the biological environment of repaired tendons and ligaments by the administration of growth factors can lead to improved structural properties compared to control. Our central hypothesis is that the delivery of selected growth factors at the site and time of mid-substance tendon and tendon to bone suture, will enhance cellular proliferation and matrix synthesis, leading to a stiffer and stronger repair. Scientific studies have shown that growth factor delivery by bolus injection results in fluctuations in tissue and serum concentrations, with inconsistent effects on local tissues. Recent reports have described improved results when growth factor administration was maintained for a prolonged interval after operative repair. We hypothesize that the utilization of novel delivery systems that provide for the sustained release of growth factors, extending their effectiveness through the early stages of repair, will improve the healing properties of sutured tendons and tendon to bone insertion sites under conditions of controlled passive motion rehabilitation. Based on results from preliminary studies, in specific Aims 1 and 2 we will evaluate the kinetics of administration of PDGF-BB, bFGF, and BMP-2 coupled with a sustained delivery system in vitro (Aim 1) and in vivo (Aim 2). In Aims 3 and 4, we will study the effects of administration of PDGF-BB and bFGF on mid-substance tendon healing (Aim 3), and BMP-2 on insertion site healing (Aim 4), by assessing the maturity, and the strength and stiffness of the repair tissue. Taken together, these studies will establish a biological basis for improved healing through the stimulation of those intrinsic cellular processes that lead to cell replication, neovascularization, matrix synthesis, and tissue remodeling. They will extend our understanding of the critical early stages of healing and will provide therapeutic solutions for the most prevalent clinical problems associated with tendon injury and repair.