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、工作能力丧失和生活质量下降有关。在体力活动人群(例如，跑步者)中，AT损伤的终生累积发病率超过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的发生率仍超过10%。快速和充分的肌腱到骨骼的愈合是治疗受伤患者的关键因素。手术重建依赖于两种形态和生物力学性质截然不同的组织(骨和肌腱)的固定，并在早期恢复时依靠新骨形成将肌腱固定在骨隧道内。拟议的项目旨在通过在重建部位局部应用甲状旁腺激素结合肽(PTH)来促进肌腱的骨整合。尽管甲状旁腺素在骨质疏松症患者中的全身应用是一种被接受、批准和广泛使用的治疗方法，但由于副作用，其治疗周期被限制在2年内。根据我们之前的研究，我们将检验局部应用PTH结合肽是否会导致损伤修复后肌腱到骨的附着部位局部内源性PTH浓度增加。目前，还没有可用于局部结合甲状旁腺激素的缝合材料。因此，我们开发了一种含有共价结合PTH结合肽的生物活性外科缝合材料。在以前的研究中已经建立了多肽以及共价结合的程序。创伤部位甲状旁腺激素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素的作用。富含甲状旁腺素结合肽的缝合材料将应用于跟腱损伤大鼠模型。以下对肌腱-骨界面的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。成像将使用微型CT进行。含甲状旁腺素结合肽的生物活性缝合材料在跟腱损伤愈合过程中的积极作用可能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.