An osteogenesis mimicking biomineralized bone adhesive for rapid skeletal regeneration.

Osteogenesis is a crucial process in bone injury repair where osteoblasts mineralize collagen to form new bone at the fracture site. For effective bone regeneration in comminuted fractures, it is essential to develop an osteogenic bone adhesive that can be applied at the time of fixation to temporarily immobilize fragmented bone pieces. We present a flowable, injectable adhesive that enables on-demand bonding of irregular fracture surfaces and, after photocuring, provides enhanced mechanical integrity while supporting osteogenesis. To meet these clinical requirements, we engineered a gelatin methacryloyl-polyethylene glycol diacrylate (GelMA-PEGDA) network bone adhesive that undergoes rapid photocuring to enable on-demand bonding and immediate mechanical stabilization at the fracture site. By incorporating nanoscale hydroxyapatite (nHA) to confer a bone-mineral-mimetic composition and biomineralization capacity, the photocured adhesive promotes bone marrow-derived mesenchymal stem cell recruitment and supports skeletal regeneration. During degradation, the organic-inorganic phase of the adhesive can guide osteogenesis, leading to satisfactory healing outcomes in fractures. Overall, the compositional and mechanical biomimicry, photosensitivity and osteogenic potential of GelMA-nHA-PEGDA render it a potential all-in-one solution for minimally invasive treatment of multiple skeletal diseases.