Making connections: using anatomy to guide tissue engineering approaches at the enthesis.

The enthesis demonstrates a distinct highly ordered zonal microanatomy at the osteotendinous/osteoligamentous tissue connection that allows for the smooth transmission of mechanical forces between tissues. Interfacial tissue engineering (ITE), a subset of the interdisciplinary field of tissue engineering, is directed at replicating this complex transitional anatomy of the enthesis in vitro. Yet, the limited understanding of tissue boundaries, gradients and structural relationships at specific anatomical locations hampers the development of novel therapeutic strategies for bespoke enthesis regeneration, thus reducing their direct clinical applicability. This review provides an overview of ITE approaches for repair of the osteotendinous/osteoligamentous junction and highlights the importance of complementary inclusion of direct anatomical research. The cross-disciplinary collaboration across an array of experts, including anatomists, involved in the design, development and utilisation of bioengineered tissues will enhance the properties of such tissues and improve their clinical relevance. More specifically, a detailed anatomical analysis of the region of interest should drive the in vitro design and enable researchers to develop anatomically and clinically relevant tissue-engineered replacement tissues for human implantation. Finally, the present review discusses the challenges and future directions of the ITE field and highlights the importance of anatomically driven tissue engineering as an emerging tool in clinical translational research.