FLEXOR TENDON HEALING

描述（由申请人提供）：三分之一的工人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。实验和临床研究报道，在初级肌腱和肌腱与骨缝合后，修复部位伸长和粘连形成的发生率很高，修复部位失败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，通过施用生长因子改变修复后的肌腱和韧带的生物环境可导致结构特性的改善。我们的中心假设是，在中间物质肌腱和肌腱到骨缝合线的位置和时间输送选定的生长因子，将增强细胞增殖和基质合成，导致更硬、更强的修复。科学研究表明，通过大剂量注射给药生长因子会导致组织和血清浓度的波动，对局部组织的影响不一致。最近的报道描述了在手术修复后长时间维持生长因子治疗的改善结果。我们假设，利用新的递送系统，提供生长因子的持续释放，在修复的早期阶段延长其有效性，将在受控被动运动康复的条件下改善缝合肌腱和肌腱到骨插入部位的愈合特性。基于初步研究的结果，在特定的Aims 1和2中，我们将评估PDGF-BB、bFGF和BMP-2联合持续给药系统在体外（Aim 1）和体内（Aim 2）给药的动力学。在Aims 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对中间物质肌腱愈合（Aim 3）和BMP-2对插入部位愈合（Aim 4）的影响。综上所述，这些研究将为通过刺激导致细胞复制、新生血管、基质合成和组织重塑的内在细胞过程来改善愈合建立生物学基础。他们将扩展我们对关键的早期愈合阶段的理解，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.