Dexamethasone loaded injectable, self-healing hydrogel microspheresbased on UPy-functionalized Gelatin/ZnHAp physical...

Biopolymer-based injectable hydrogels provide great potential as bone tissue engineering (BTE) scaffolds on account of biocompatibility, and pore interconnectivity that enables delivery of cells and/or signaling molecules for bone repair. Recently, Gelatin hydrogels based on H-bonds were considered in response to concerns around the chemical crosslinking agents. In this study, a self-healing gelatin hydrogel with remarkable compressive and self-healing properties was prepared via formation of quadruple hydrogen bonds between ureidopyrimidinon functional groups, which were substituted on NH₂ groups of gelatin(GelUPy). Degree of substitution controls properties of the resulting hydrogel from a shape- memory hydrogel (100% substitution), to a hydrogel (about 80%), to this self-healing hydrogel (about 40%). We report a strategy that adopts an emulsion synthesis approach to delivery of dexamethasone and Ca/Zn ions from injectable self-healing GelUPy hydrogel (GelUPy-ZnHApUPy-DEX), to induce osteogenic differentiation of adipose-derived stem cells, in vitro, and enhance bone regeneration in a cranial bone defect in a rat model. We show that key properties of the composite hydrogels, including mechanical properties, and release behavior of DEX are a match to the requirements of BTE. Overall, our results demonstrate that this self-healing gelatin approach is a promising strategy to enhance bone regeneration through a minimally invasive procedure.