Covalently Adaptable Hydrogel Based on Hyaluronic Acid and Poly(γ-glutamic acid) for Potential Load-Bearing Tissue Engineering

Reversibly cross-linked adaptable hydrogels show great advantages in tissue engineering. The dynamic adaptable networks can overcome three-dimensional (3D) physical restrictions to enable normal cellular functions without hydrogel degradation. However, because of the dynamic reversibility, adaptable hydrogels typically exhibit weak mechanical properties and rapid erosion behaviors. Herein, we develop a facile strategy to prepare stable adaptable hydrogels using dynamic covalent chemistry, stable covalent chemistry, and the interpenetrating polymeric network (IPN) strategy. The developed IPN HA/gamma-PGA adaptable hydrogels have stable structures, good mechanical properties, enzymatic degradability, and injectability. Compression test indicates that although containing 95% water, the IPN HA/gamma-PGA adaptable hydrogels can suffer more than 85% compressive strain and show a fast shape recovery capacity and good antifatigue ability. Benefitting from the good cytocompatibility of functionalized HA and gamma-PGA and the mild preparation process of IPN HA/gamma-PGA adaptable hydrogels, NIH 3T3 cells can tolerate the 3D encapsulation process and show high cell viability. Therefore, owing to their desirable properties, the developed HA/gamma-PGA adaptable hydrogels have great potential applications for load-bearing tissue engineering.