Investigating materials and orientation parameters for the creation of a 3D musculoskeletal interface co-culture model

Musculoskeletal tissue interfaces are a common site of injury in the young, active populations. In particular, the interface between the musculoskeletal tissues of tendon and bone is often injured and to date, no single treatment has been able to restore the form and function of damaged tissue at the bone–tendon interface. Tissue engineering and regeneration hold great promise for the manufacture of bespoke in vitro models or implants to be used to advance repair and so this study investigated the material, orientation and culture choices for manufacturing a reproducible 3D model of a musculoskeletal interface between tendon and bone cell populations. Such models are essential for future studies focussing on the regeneration of musculoskeletal interfaces in vitro. Cell-encapsulated fibrin hydrogels, arranged in a horizontal orientation though a simple moulding procedure, were shown to best support cellular growth and migration of cells to form an in vitro tendon–bone interface. This study highlights the importance of acknowledging the material and technical challenges in establishing co-cultures and suggests a reproducible methodology to form 3D co-cultures between tendon and bone, or other musculoskeletal cell types, in vitro.