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 in situ mineralization of bone-like nano-HAP
in hydrogels. The resulting biomimetic osteogenic hydrogel (BOH) promotes
bone mineralization, construction of immune microenvironment, and
angiogenesis improvement in vitro. The BOH exhibited
acceleration of osteogenesis in vivo, 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 in situ 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.