FLEXOR TENDON HEALING

描述（由申请人提供）：工人中三分之一的急性损伤发生在上肢，其中很大一部分是开放性伤口，需要进行广泛的肌腱手术。实验和临床研究报告了初次肌腱和肌腱-骨缝合后修复部位延长和粘连形成的高发生率，修复部位失效最常发生在修复后的前三周。最近的研究表明，与对照组相比，通过给予生长因子改变修复肌腱和韧带的生物环境可以改善结构特性。我们的中心假设是，在中间物质肌腱和肌腱与骨缝合的部位和时间递送选定的生长因子，将增强细胞增殖和基质合成，导致更硬和更强的修复。科学研究表明，通过推注的生长因子递送导致组织和血清浓度的波动，对局部组织的影响不一致。最近的报告描述了手术修复后长时间维持生长因子给药的改善结果。我们假设，利用新型输送系统，提供生长因子的持续释放，延长其有效性，通过修复的早期阶段，将改善缝合肌腱和肌腱骨插入部位的条件下，受控的被动运动康复的愈合性能。基于初步研究的结果，在特定的目的1和2中，我们将评估PDGF-BB、bFGF和BMP-2与体外（目的1）和体内（目的2）持续递送系统偶联的给药动力学。在目标3和4中，我们将通过评估修复组织的成熟度、强度和刚度，研究PDGF-BB和bFGF给药对中间体肌腱愈合（目标3）以及BMP-2给药对插入部位愈合（目标4）的影响。总之，这些研究将通过刺激导致细胞复制、新血管形成、基质合成和组织重塑的内在细胞过程来建立改善愈合的生物学基础。他们将扩展我们对愈合关键早期阶段的理解，并将为与肌腱损伤和修复相关的最普遍的临床问题提供治疗解决方案。

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.