Self-healing of hyaluronic acid to improve in vivo retention and function

Convergent advances in the field of soft matter, macromolecular chemistry, and engineering have led to the development of biomaterials that possess autonomous, adaptive, and self-healing characteristics similar to living systems. These rationally designed biomaterials could surpass the capabilities of their parent material. Herein, we describe the modification of hyaluronic acid (HA) molecules to exhibit self-healing properties and studied its physical and biological function both in vitro and in vivo. Our in vitro findings showed that self-healing HA designed to undergo autonomous repair improved lubrication, enhanced free radical scavenging, and resisted enzymatic degradation compared to unmodified HA. Longitudinal imaging following intra-articular injection of self-healing HA showed improved in vivo retention despite the low molecular weight. Concomitant with these functions, intra-articular injection of self-healing HA mitigated anterior cruciate ligament injury-mediated cartilage degeneration in rodents. This proof-of-concept study shows how incorporation of functional properties like self-healing can be used to surpass the existing capabilities of biolubricants.