Bioinspired self-healing injectable nanocomposite hydrogels based on oxidized dextran and gelatin for growth-factor-free bone regeneration.

Hydrogels with great biocompatibility, biodegradability, and mechanical properties, combined with osteoconductivity, osteoinductivity, and osteointegration as biomaterials for bone regeneration without adding exogenous growth factors and cells are highly appealing but challenging. Here, inspired by organic-inorganic analogues of natural bone tissue and the adhesion chemistry of mussels, nanocomposite hydrogels with self-healing, injectable, adhesive, antioxidant, and osteoinductive properties (termed GO-PHA-CPs) were constructed by Schiff base cross-linking between dopamine-modified gelatin (Gel-DA) and oxidized dextran (ODex). Furthermore, the hydrogel network was enhanced by the introduction of polydopamine-functionalized nanohydroxyapatite (PHA) by improving the interfacial compatibility between the rigid inorganic particles and the flexible hydrogel matrix. Bioactive cod peptides (CPs) with osteogenic activity from Atlantic cod were further incorporated into the nanocomposite hydrogel. As a result, the multicomponent nanocomposite hydrogel favored the adhesion and spreading of MC3T3-E1 cells. The increased ALP activity suggested that GO-PHA-CPs hydrogels contributed to the osteogenic differentiation of MC3T3-E1 cells. The suitability of GO-PHA-CPs hydrogels for enhancing bone regeneration in vivo was further confirmed by the rat femoral defect model. Our results indicate that the multifunctional GO-PHA-CPs nanocomposite hydrogels without growth factors are a promising and effective candidate material for bone regeneration.