Injectable hyaluronic acid/hydroxyapatite composite hydrogels as cell carriers for bone repair

The natural polysaccharide/hydroxyapatite hydrogels are of great interest to bone tissue engineering, but the interfacial mismatch between rigid hydroxyapatite and soft polysaccharide phase in these hydrogels remains unsolved, which is unfavorable to achieving uniform dispersion of hydroxyapatite particles in the hydrogel matrices. Herein, hyaluronic acid (Hya), an extracellular matrix constituent, was chosen as the template for biological mineralization to synthesize Hya/hydroxyapatite hybrid particles (HAHs). The oxidized Hya/hydroxyapatite hybrid particles (OHAHs) were obtained by oxidating the Hya in the HAHs. These OHAHs were the ball-flower particles hybridized with ca. 22 % oxidized Hya. Then, different concentrations of OHAHs were introduced to prepare hydroxyapatite composite hydrogels (HCH) via Schiff-base reaction of oxidized Hya and carboxymethyl chitosan. The injectability and self-healing of HCH were evaluated and the introduction of OHAHs significantly increased the storage modulus. The gelation time of HCH showed a negative relation with the concentration of OHAHs while the storage modulus presented a positive correlation. MTT assays and live/dead staining of L929 cells co-cultured with HCH confirmed that the hydrogels had excellent cytocompatibility, and supported the adhesion and proliferation of cells under the three-dimension culture conditions. These injectable self-healing hydrogels suitable for cell encapsulation were potentially useful for bone defect repair.