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

Shoulder pain affects approximately 20% of the population at any one time and is mainly caused by tears in the rotator cuff tendon. The current gold standard treatment for rotator cuff tendon tears in the shoulder is surgical repair. However, surgical repair of the tendon can fail due to lack of tendon healing with risk of failure doubling 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 tendon to bone leads to failure for a high proportion of patients. To overcome this problem, we will combine our knowledge in advanced materials, cell biology and biofabrication and develop a new therapy capable of promoting the biological regeneration of the tendon/bone interface. First, we will produce a range of natural materials with tuneable physicochemical properties capable of matching those of the native bone and tendon tissues. Using biofabrication techniques we will then generate 3D scaffolds capable of replicating the functionally graded organization of the native tendon/bone interface. The ability of the scaffolds to promote the regeneration of torn tendons will be assessed in vitro with undifferentiated/differentiated cells using established protocols and in collaboration with our clinical team.

Background:

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.

Questions to be answered:

1. Can we generate PHAs with physical, chemical and biological properties to mimic those of the native tissues (i.e. bone and tendon)?
2. Can we develop biofabrication methods to generate 3D scaffolds with functional gradients to mimic the native tendon/bone interface?
3. Can our engineered scaffolds improve the functional regeneration of damaged tendons compared to the current golden standards?
4. Can our engineered scaffolds be optimised to become suitable for surgical implantation onto native tendon tissue?