CFN Colloquium

Musculoskeletal joint motion is facilitated by synchronized interactions between a variety of connective tissues and specifically, the seamless integration of bone with soft tissues such as tendons, ligaments or cartilage. Many of these soft tissues transit into bone through a narrow, multi-region interface that is surprisingly complex at the microscale. This transition, also called the enthesis or insertion, serves to minimize the formation of stress concentrations while enabling load transfer between soft and hard tissues. Given its functional significance, re-establishment of the enthesis is thus critical for promoting the integrative repair of soft tissue grafts, and are foundational for the design of organs-on-chip and other complex tissue platforms. To this end, multiphasic scaffolds with microscale compositional and mechanical gradients have been explored extensively to impart spatial control over cell crosstalk and cell-material interactions for multi-tissue regeneration. These efforts are inspired by elucidation of the native enthesis structure-function relationship and using the classic rotator cuff tendon-to-bone insertion as an example, nanomaterial-based strategies for interface regeneration and homeostasis will be discussed, with a focus on strategic biomimicry to avoid over-engineering while ensuring functional integration.