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

肩关节疼痛在任何时候都会影响大约20%的人群。肩袖肌腱撕裂占肩部疼痛原因的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，由于缺乏肌腱愈合，退化肌腱的手术修复可能失败。这种失败的风险在50至70岁之间的发生率翻了一番。因此，目前的治疗方法和潜在的病理学之间存在脱节，因为退化肌腱与骨的机械结合导致高比例患者的失败。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（即聚羟基烷酸酯-PHA），其具有可调的组成和抗菌特性，以模拟天然骨/肌腱组织的生物、化学和物理特性。为了改善缺损部位的生物力学耦合并增强功能再生，我们将制造具有能够复制天然肌腱/骨界面的印迹功能梯度的支架。这将使用多材料3D生物打印和熔融静电纺丝技术来实现。将使用未分化的间充质干细胞和其他市售细胞系在体外评估支架的性能。我们将与我们的临床团队和工业合作伙伴密切合作，评估如何将新开发的产品从工作台转移到床边。

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.