<i>In Situ</i> Biomimetic Mineralization of Bone-Like Hydroxyapatite in Hydrogel for the Acceleration of Bone Regeneration

Abstract

A critical-sized bone defect, which cannot be repaired through self-healing, is a major challenge in clinical therapeutics. The combination of biomimetic hydrogels and nano-hydroxyapatite (nano-HAP) is a promising way to solve this problem by constructing an osteogenic microenvironment. However, it is challenging to generate nano-HAP with a similar morphology and structure to that of natural bone, which limits the improvement of bone regeneration hydrogels. Inspired by our previous works on organic-inorganic cocross-linking, here, we built a strong organic-inorganic interaction by cross-linking periosteum-decellularized extracellular matrix and calcium phosphate oligomers, which ensured the <i>in situ</i> mineralization of bone-like nano-HAP in hydrogels. The resulting biomimetic osteogenic hydrogel (BOH) promotes bone mineralization, construction of immune microenvironment, and angiogenesis improvement <i>in vitro</i>. The BOH exhibited acceleration of osteogenesis <i>in vivo</i>, achieving large-sized bone defect regeneration and remodeling within 8 weeks, which is superior to many previously reported hydrogels. This study demonstrates the important role of bone-like nano-HAP in osteogenesis, which deepens the understanding of the design of biomaterials for hard tissue repair. The <i>in situ</i> mineralization of bone-like nano-HAP emphasizes the advantages of inorganic ionic oligomers in the construction of organic-inorganic interaction, which provides an alternative method for the preparation of advanced biomimetic materials.