Post-Implantation Stiffening by a Bioinspired, Double-Network, Self-Healing Hydrogel Facilitates Minimally Invasive Cell Delivery for Cartilage Regeneration

Injectablehydrogels have demonstrated advantages in cartilagerepair by enabling the delivery of cells through a minimally invasiveapproach. However, several injectable hydrogels suffer from rapiddegradation and low mechanical strength. Moreover, higher mechanicalstiffness in hydrogels can have a detrimental effect on post-implantationcell viability. To address these challenges, we developed an in situforming bioinspired double network hydrogel (BDNH) that exhibits temperature-dependentstiffening after implantation. The BDNH mimics the microarchitectureof aggrecan, with hyaluronic acid-conjugated poly(N-isopropylacrylamide) providing rigidity and Schiff base crosslinkedpolymers serving as the ductile counterpart. BDNHs exhibited self-healingproperty and enhanced stiffness at physiological temperature. Excellentcell viability, long time cell proliferation, and cartilage specificmatrix production were observed in the chondrocytes cultured in theBDNH hydrogel. Evidence of cartilage regeneration in a rabbit cartilagedefect model using chondrocyte-laden BDNH has suggested it to be apotential candidate for cartilage tissue engineering.

Automated summary

Injectable hydrogels have been used for cartilage repair, but some of them have issues with rapid degradation and low mechanical strength. To address these challenges, a bioinspired double network hydrogel (BDNH) was developed, which exhibits temperature-dependent stiffening after implantation. The BDNH showed excellent cell viability, long time cell proliferation, and cartilage specific matrix production, making it a potential candidate for cartilage tissue engineering.