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

肌腱-骨界面复合体的损伤，如跟腱（AT）损伤是常见的，并与相当大的发病率，丧失工作能力，降低生活质量。AT损伤在体力活动人群中的终生累积发病率超过50%（例如，跑步者）。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的发生率仍超过10%。快速和充分的肌腱-骨愈合是治疗受伤患者的关键因素。外科重建依赖于两种组织（骨和肌腱）的固定，而这两种组织的形态和生物力学特性截然不同，并依赖于新骨的形成，以在早期恢复期间将肌腱锚在骨隧道中。拟议的项目旨在通过局部施用甲状旁腺激素结合肽（PTH）到重建部位来增强肌腱的骨整合。虽然PTH在骨质疏松症患者中的全身应用是一种可接受、批准和广泛使用的治疗方法，但由于副作用，其治疗持续时间仅限于2年。根据我们以前的研究，我们将测试的假设是否局部应用PTH结合肽导致增加的内源性PTH的局部浓度内的肌腱-骨插入部位损伤修复后。目前，没有可用于局部结合PTH的缝线材料。因此，我们开发了一种生物活化的外科缝合材料，其中含有共价结合的PTH结合肽。在先前的研究中建立了肽以及共价结合的程序。PTH在损伤部位的间歇性存在对骨代谢具有合成代谢作用。PTH结合肽的使用将使我们能够利用内源性PTH的作用。富含PTH结合肽的缝线材料将应用于跟腱损伤大鼠模型。肌腱-骨界面的以下分析将包括生物力学研究、组织学和遗传学分析以及蛋白质分析。将使用micro-CT进行成像。使用含有PTH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可以为临床应用铺平道路。

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.