Utilizing natural biological scaffold for enhancement of tendon healing

肌腱撕裂是常见的肌肉骨骼损伤，可以在不恢复功能结构的情况下愈合。 修复肌腱不能恢复功能结构会导致损伤的进展和高发病率 手术修复后再次撕裂。无疤痕肌腱愈合，恢复了原有的组织特性，可以改善 手术结果或完全不需要手术修复，但通常不会在产后观察到 哺乳动物。成年Murphy Roths大鼠(MRL/MPJ)表现出再生能力的发现 将这种小鼠品系作为一种令人兴奋的模型来研究成年再生的基础机制 治愈。对MRL/MPJ小鼠再生机制的研究产生了以下假设 全身和局部组织水平都有牵连，但没有确凿数据。家长授权审问 MRL/MPJ小鼠的全身环境和肌腱局部环境对其功能的影响 无疤痕肌腱愈合。利用新的显微外科技术和近交系小鼠品系来分离 全身环境和固有肌腱在无疤痕肌腱愈合中的作用。肌腱器官培养 也被用来确定再生MRL/MPJ的临时细胞外基质(ECM)的作用 小鼠在调节导致无疤痕肌腱愈合的细胞活动中的作用。我们的发现表明，先天的 肌腱的环境对提高MRL/MPJ肌腱的愈合能力至关重要。这是 器官培养中间物质穿孔MRL/MPJ肌腱的事实证明，其中系统的 消除了环境，表现出比B6更好的力学性能和组织恢复 肌腱。父母基金还开始探索从以下来源获得的临时ECM的治疗潜力 MRL/MPJ愈合肌腱促进瘢痕介导的B6小鼠的无疤痕肌腱愈合。更具体地说， 愈合的MRL/MPJ和B6肌腱的临时ECM将被收获，脱细胞，悬吊在 给药凝胶，放入损伤的B6小鼠的膝腱(PT)的中间物质中。这个 补充剂通过确定蛋白质和结构，扩展了父母拨款中提出的研究 与改善治疗结果相关的成分。更具体地说，这种蛋白质 与B6小鼠最佳和最差愈合结果相关的临时ECM的组成将 使用蛋白质组学进行广泛评估。此外，与最佳组合物相关联的结构 将在粉碎前使用透射电子显微镜(TEM)从愈合的MRL/MPJ中确定。 未来的研究将使用父母资助(器官培养)中开发的工具和补充的数据 确定促进愈合的蛋白质或蛋白质网络。此外，结构数据将用于 通知未来交付脚手架的结构设计。总而言之，附录中的数据将是有用的 将父母资助的研究成果转化为治疗学。

Tendon tears are common musculoskeletal injuries that heal without restoration of the functional structure. Failure of healing tendons to restore the functional structure leads to progression of injury and high incidence of re-tear after surgical repair. Scarless tendon healing, with restored native tissue properties, could improve surgical outcome or eliminate the need for surgical repair altogether, but is not typically observed in post-natal mammals. The discovery that adult Murphy Roths Large (MRL/MpJ) mice exhibit a regenerative capacity has distinguished this mouse strain as an exciting model to investigate mechanisms that underlie adult regenerative healing. Investigation into the regenerative mechanisms of MRL/MpJ mice has generated hypotheses that implicate both, the systemic and local tissue level, but no conclusive data exists. The parent grant interrogates the contribution of the systemic environment of the MRL/MpJ mouse and the local environment of its tendon to scarless tendon healing. Novel microsurgical techniques and inbred mouse strains are utilized to uncouple the contribution of the systemic environment and the innate tendon to scarless tendon healing. Tendon organ culture is also employed to determine the role of the provisional extracellular matrix (ECM) from regenerative MRL/MpJ mice in modulating the cellular activity that leads to scarless tendon healing. Our findings show that the innate environment of the tendon is essential to the improved healing capacity of the MRL/MpJ tendon. This is evidenced by the fact that organ cultured midsubstance punched MRL/MpJ tendons, wherein the systemic environment is eliminated, exhibit superior recovery of the mechanical properties and the structure than B6 tendons. The parent grant also begins to explore the therapeutic potential of the provisional ECM derived from MRL/MpJ healing tendons to promote scarless tendon healing in scar-mediated B6 mice. More specifically, the provisional ECM from healing MRL/MpJ and B6 tendons will be harvested, decellularized, suspended in a delivery gel and placed in midsubstance punch injured patellar tendons (PT) of scar-mediated B6 mice. The supplement extends the studies proposed in the parent grant by determining the protein and structural composition that are associated with an improved therapeutic outcome. More specifically, the protein composition of the provisional ECM that is associated with the best and worst healing outcomes in B6 mice will be extensively evaluated using proteomics. Furthermore, the structure associated with the optimal composition will be determined from healing MRL/MpJ using Transmission Electron Microscopy (TEM), prior to pulverization. Future studies will use the tools developed in the parent grant (organ culture) and the data from supplement to identify the proteins or network of proteins that promote healing. In addition, the structural data will be used to inform structural design of future delivery scaffolds. In summary, data from the supplement will be instrumental in translating findings from the parent grant into therapeutics.