Regenerating the rotator cuff tendon-to-bone interface through biofabrication

肩痛在任何时候都影响着大约20%的人。肩袖肌腱撕裂占肩膀疼痛的40%。目前治疗肩袖肌腱撕裂的金标准是手术修复。然而，在22%的病例中，手术修复退行性肌腱会因缺乏肌腱愈合而失败。在50至70岁之间，这种失败的风险会增加一倍。因此，目前的治疗方法与潜在的病理之间存在脱节，因为退行性肌腱与骨的机械缝合导致很大比例的患者失败。该项目旨在提供一种新的基于支架的治疗方法，具有增强的生物学特性，以支持撕裂肌腱的功能性再生并提高愈合率。在先前工作的基础上，我们将生产细菌来源的生物材料（即聚羟基酸盐- pha），具有可调的成分和抗菌特性，以模仿天然骨/肌腱组织的生物、化学和物理特性。为了改善缺陷部位的生物力学耦合并增强功能再生，我们将制造具有印迹功能梯度的支架，能够复制天然肌腱/骨界面。这将通过使用多材料3D生物打印和熔融静电纺丝技术来实现。支架的性能将在体外使用未分化的间充质干细胞和其他市售细胞系进行评估。在与我们的临床团队和工业合作伙伴的密切合作下，我们将评估如何将新开发的产品从实验室转化为床侧。

Shoulder pain affects approximately 20% of the population at any one time. A tear in the rotator cuff tendon accounts for 40% of the causes of shoulder pain. The current gold standard treatment for rotator cuff tendon tears in the shoulder is surgical repair. However, surgical repair of the degenerate tendon can fail due to lack of tendon healing in 22% of cases. This risk of failure doubles in incidence between 50 and 70 years. Thus, there is a disconnect between current treatment methods and the underlying pathology as mechanical suturing of the degenerate tendon to bone leads to failure for a high proportion of patients. This project aims to deliver a new scaffold-based therapy with enhanced biological properties to support the functional regeneration of the torn tendon and improve healing rates. Building on previous work we will produce biomaterials from bacterial origin (i.e. Polyhydroxyalcanoates - PHAs) with tuneable composition and anti-bacterial features to mimic the biological, chemical and physical properties of native bone/tendon tissues. To improve biomechanical coupling at the defect site and enhance functional regeneration, we will fabricate scaffolds with imprinted functional gradients capable of replicating the native tendon/bone interface. This will be achieved using multi-material 3D bioprinting and melt-electrospinning techniques. The performance of the scaffolds will be assessed in vitro using undifferentiated mesenchymal stem cells and other commercially available cell lines. In close collaboration with our clinical team and industrial partner, we will evaluate how to translate the newly developed product from the bench to the bed side.