The enthesis is a highly specialised tissue interface that enables efficient transfer of mechanical loads between compliant tendon and stiff bone. Its function arises from gradual variations in collagen organisation, mineral content, cellular phenotype and mechanical properties. Following injury or surgical repair, this complex gradient can be disrupted, resulting in the formation of mechanically inferior scar tissue and an increased risk of failure. Recreating the compositional and mechanical gradients of the native enthesis therefore represents an important challenge in musculoskeletal tissue engineering.
This PhD project will investigate the development of compositionally graded collagen-based foams combined with physiologically relevant mechanical stimulation using robotic bioreactors. Gradients may include collagen density, fibre organisation, mineral content and incorporation of additional extracellular matrix components. Manufacturing approaches will be developed to create continuous rather than sharply separated regions, progressing from compliant tendon-like material through an intermediate fibrocartilage-like zone towards a mineralised bone-like region.
The graded scaffolds will subsequently be integrated within a soft bioreactor platform capable of reproducing physiologically relevant loading conditions. Various loading regimes will be applied to investigate how local scaffold composition and mechanical stimulation interact to influence cell behaviour. Human cells will be used to assess viability, matrix deposition and spatial expression of markers.
A key objective will be to determine whether mechanical conditioning can enhance or stabilise the engineered composition gradient and promote the formation of distinct but continuously connected tissue regions. The resulting platform could provide both a regenerative strategy for tendon-to-bone repair and an advanced in vitro model for studying enthesis development, injury and healing.
