Engineered Injectable Cell-Laden Chitin/Chitosan Hydrogel with Adhesion and Biodegradability for Calvarial Defect Regeneration.

Trade-off of high-strength and dynamic crosslinking of hydrogels remains an enormous challenge. Motivated by the self-healing property of biological tissues, the strategy of combining multiple dynamic bond mechanisms and a polysaccharide network is proposed to fabricate biomimetic hydrogels with sufficient mechanical strength, injectability, biodegradability, and self-healing property for bone reconstruction engineering. Stable acylhydrazone bonds endowed hydrogels with robust mechanical strength (>10 kPa). The integration of dynamic imine bonds and acylhydrazone bonds optimized the reversible characteristic to protect the cell during the injection and mimicked ECM microenvironment for cell differentiation as well as rapid adapting bone defect area. Furthermore, due to the slow enzymatic hydrolysis kinetics of chitosan and the self-healing properties of resulting networks, hydrogels exhibited a satisfactory biodegradation period (>8 weeks) that highly matches with bone regeneration. Additionally, rBMSC-laden hydrogels exhibited splendid osteogenic induction and bone reconstruction without prefabrication scaffolds and incubation, demonstrating tremendous potential for clinical application. This work proposes an efficient strategy for the construction of a low-cost multifunctional hydrogel, making polysaccharide-based hydrogels as the optimal carrier for enabling cellular functions in bone repair.