Synthesis and characterization of injectable self-healing hydrogels based on oxidized alginate-hybrid-hydroxyapatite nanoparticles and carboxymethyl chitosan

Injectable hydrogels are of great interest in tissue engineering, and those incorporating hydroxyapatite (HA) are especially acclaimed in the application of bone repair. Synthetic micro-HA were generally used for this purpose and in some cases, surface modification of HA was further applied to improve the interfacial compatibility of rigid inorganic HA with soft organic matrix. In this study, the injectable hydrogels based on oxidized alginate hybrid HA nanoparticles and carboxymethyl chitosan were achieved via Schiff base reaction. Physicochemical characterization confirmed that oxidized HA/Alg hybrids (OHAH) were successfully prepared. Rheological measurements verified the formation of hydrogels based on the dynamic imine bonding, and the gelation time showed a negative correlation to the concentration and oxidation time of OHAH, while the storage moduli exhibited a positive correlation. The self-healing property of these hydrogels was validated by the splicing experiments and rheological experiments. The lyophilized hydrogels showed porous structures with numerous HA nanoparticles distributed on the surface of pore wall. MTT assays and live/dead staining of cell experiments confirmed the cytocompatibility of these hydrogels. The injectable hydrogels with self-healing and tunable gelling properties were ingeniously prepared with functionalized alginate-mediated HA hybrid nanoparticles, and these hydrogels are promising for applications in bone tissue engineering.