Engineering smart light-triggered bone-targeting nanocarriers for promoting bone repair

Nonunion or impaired fracture healing represents a prevalent clinical challenge, necessitating urgent intervention and leading to persistent pain, functional disability, and diminished quality of life. Bone tissue engineering holds transformative potential for managing such conditions; however, achieving spatiotemporally controlled release of osteoinductive factors remains a major hurdle, as subtherapeutic dosing compromises efficacy while excessive amounts risk ectopic ossification. To address this, we engineered a smart, asymmetric porous hollow nanocarrier (APHC) with Asp₈ surface modification (A-APHC) for bone-specific targeting. This system co-delivers bone morphogenetic protein-2 (BMP-2) and stromal cell-derived factor-1 (SDF-1). The A-APHC platform enables light-triggered, controlled release of BMP-2 to drive osteogenesis, while SDF-1 potentiates bone repair by recruiting bone marrow mesenchymal stem cells via the CXCR4 axis. Both in vitro and in vivo assessments confirmed the robust osteogenic capability of A-APHC@SDF/BMP. This nanotherapeutic strategy not only facilitates early healing of bone defects but also mitigates the risk of secondary complications associated with prolonged nonunion, demonstrating significant promise as a targeted and quantifiable approach to bone regeneration.