The impact of PTH on the healing of the tendon-to-bone insertion site - A rodent model

跟腱-骨界面复合体损伤，如跟腱（AT）损伤是常见的，并与相当高的发病率、工作能力丧失和生活质量下降有关。在体力活动人群（如跑步者）中，AT损伤的终生累积发生率超过50%。尽管手术技术和缝合材料不断改进，但跟腱重建术后并发症发生率仍超过10%。快速和充分的肌腱-骨愈合是治疗受伤患者的关键因素。手术重建依赖于形态和生物力学特性截然不同的两种组织（骨和肌腱）的固定，并依赖于新生骨形成在早期恢复时将肌腱锚定在骨隧道中。该项目旨在通过在重建部位局部施用甲状旁腺激素结合肽（PTH）来增强肌腱的骨整合。虽然骨质疏松症患者全身应用甲状旁腺激素是一种被接受、批准和广泛使用的治疗方法，但由于其副作用，其治疗时间限制在2年。根据我们之前的研究，我们将检验局部应用甲状旁腺激素结合肽是否会导致损伤修复后肌腱-骨插入部位局部内源性甲状旁腺激素浓度增加的假设。目前，没有可用的缝合材料，使PTH的局部结合。因此，我们开发了一种生物活性的外科缝合材料，它含有共价结合的甲状旁腺素结合肽。多肽和共价结合的程序在以前的研究中已经确定。PTH在损伤部位的间歇性存在对骨代谢有合成代谢作用。甲状旁腺激素结合肽的使用将使我们能够利用内源性甲状旁腺激素的作用。将含甲状旁腺素结合肽的缝合材料应用于大鼠跟腱损伤模型。接下来的肌腱-骨界面分析将包括生物力学研究，组织学和遗传分析，以及蛋白质分析。使用微型ct进行成像。含有甲状旁腺激素结合肽的生物活化缝合材料在跟腱损伤愈合过程中的积极作用为其临床应用铺平了道路。

Injuries to the tendon-to-bone interface complex such as Achilles tendon (AT) injuries are frequent and associated with considerable morbidity, loss of ability to work, and diminished quality of life. AT injuries have a lifetime cumulative incidence of more than 50% in physically active populations (e.g., runners). Despite the constant improvement of surgical techniques and suture materials, the rate of complications exceeds 10% after Achilles tendon reconstruction. Fast and sufficient tendon-to-bone healing is a key factor in the treatment of injured patients. Surgical reconstruction depends on the fixation of two tissues (bone and tendon) with vastly different morphological and biomechanical properties, and relies on new bone formation to anchor the tendon in the bone tunnel during early recovery.The proposed project aims at enhancing the osseointegration of the tendon by locally administering parathyroid hormone binding peptide (PTH) to the reconstruction site. While the systemic application of PTH in patients suffering from osteoporosis poses an accepted, approved and widely used treatment, its treatment duration is limited to 2 years because of side effects. Following our previous studies, we will test the hypothesis whether the local application of PTH-binding peptide leads to an increased local concentration of endogenous PTH within the tendon-to-bone insertion site upon injury repair. Currently, there is no suture material available, which enables the local binding of PTH. Therefore, we developed a bioactivated, surgical suture material which contains covalently bound PTH-binding peptide. The peptide as well as the procedure for covalent binding were established in previous studies. The intermittent presence of PTH at the site of injury has an anabolic effect on bone metabolism. The use of PTH-binding peptide will enable us to take advantage of the effect of endogenous PTH. The suture material enriched with PTH-binding peptide will be applied in an Achilles tendon injury rat model. The following analyses of the tendon-to-bone interface will include biomechanics studies, histological and genetic analysis, as well as protein analysis. Imaging will be performed using micro-CT. A positive effect of the use of bio activated suture materials containing PTH-binding peptide during the healing of Achilles tendon injuries could pave the way for clinical applications.