Biomineralized dipeptide self-assembled hydrogel with ultrahigh mechanical strength and osteoinductivity for bone regeneration

Peptide self-assembled hydrogels are ideal scaffolds for three-dimentional cell culture and tissue engineering due to their native extracellular matrix enabling the transport of nutrients as well as the cells growth and expansion. However, the use of peptide hydrogels in the hard tissues regeneration such as alveolar and skull bone has been largely unexplored, hindered by the insufficient mechanical strength and osteogenesis activity. Herein, peptide self-assembled nanostructures are used as templates to emulate natural biomineralization process. The vaterite nanoparticles loaded with thermolysin act as a role of mature osteoblasts secreting collagen fibrils to initiate dipeptide self-assembly as biomimetic extracellular matrix. Meanwhile, the vaterite nanoparticles with a high specific surface area form strong intermolecular and interfacial interaction with hydrogel networks, acting as a cross-linker to achieve extrafibrillar mineralization. Moreover, vaterite nanoparticles function as a mineral reservoir to release Ca2+, inducing intrafibrillar mineralization, further enhancing the mechanical property. The resulting hydrogel exhibits an unprecedently high value of storage modulus (473 kPa), excellent biocompatibility and osteoinductivity. In rat calvarial defect model, the hydrogel significantly accelerates regeneration of osteogenesis tissue, thus indicating the potential of such peptide hydrogels for application in bone regeneration.