Inhibiting Aberrant Interfacial Friction Regulates Cell Fate and Promotes Cartilage Regeneration

Aberrant interfacial friction, both within tissues and between tissues and implanted biomaterials, is an overlooked factor that can lead to suboptimal outcomes of tissue regeneration. The role of aberrant interfacial friction in modulating cell behavior and influencing tissue regeneration is poorly understood. Overall design: In this study, using cartilage as a model tissue, we demonstrated that interfacial friction was exacerbated following cartilage injury in both humans and rats, driving increased wear of the opposing articular surface. For concept validation, we engineered an automatic cell friction generating system (ACF-GenSys) to emulate the interfacial friction between implanted biomaterials and native cartilage in vitro. Our results demonstrated that aberrant frictional force was directly responsible for triggering cell apoptosis through Piezo1-dependent calcium ion influx. To mitigate these effects, we developed a super-lubricating gel (SL-Gel) that protected cells from frictional force and inhibited in vitro apoptosis. We achieved proof of concept in both rabbits and non-human primates with cartilage defects, where implantation of the SL-Gel reduced interfacial cartilage wear and enhanced defect regeneration. Using an animal model with high clinical relevance, this study unveiled the detrimental impact of interfacial friction between tissues and biomaterials on cell fate and tissue regeneration, and suggests that a super-lubricating biomaterial could enhance the outcomes of interfacial tissue regeneration in the presence of aberrant frictional forces.