Micro/nanoparticle hybrid hydrogel platform with mild photothermal stimulation on abaloparatide in situ release for cranial bone regeneration.

Repairing critical-sized bone defects is still difficult in clinical practice. Current strategies increasingly rely on bone tissue engineering to reconstruct defect sites while reducing donor-site injury associated with autografts and immunological concerns related to allografts. Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) have been acknowledged for their ability to promote skeletal repair and bone production. However, systemic administration may result in limited drug accumulation within the defect area and may also cause unwanted systemic effects. In situ drug delivery is an effective way to help bone regeneration. In addition to growth factors, physical stimuli, especially mild photothermal therapy (PTT), have emerged as outstanding strategies to promote tissue regeneration. Meanwhile, drug release can be triggered by mild PTT. As a result, abaloparatide (ABL)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared. The nanoparticles were then incorporated into hydrogels for local delivery. GO-BPEI endowed the hydrogel with mild photothermal responsiveness and heat-triggered drug-release capability. In the cranial bone defect model, the synergistic effect of ABL and mild PTT promoted neovascularization and bone regeneration, ultimately achieving significant bone repair. Overall, the micro/nanoparticle hybrid hydrogel platform with localized, controlled release of ABL provides a potentially effective new method for repairing bone defects.