Multifunctional scaffold integrating chemo/photothermal therapy and bone defect reconstruction for osteosarcoma: An...

Osteosarcoma (OS) represents the most common malignant bone tumor in adolescents. The current standard-of-care regimen combines preoperative induction chemotherapy, radical surgical resection, and postoperative consolidative chemotherapy. Emerging evidence indicates that near-infrared (NIR) light-induced hyperthermia exhibits dual therapeutic effects by inducing tumor cell apoptosis and stimulating osteogenic differentiation. Polydopamine (PDA) converts NIR light into localized heat, enabling scaffold functionalization and drug conjugation via its reactive surface. Doxorubicin (DOX) forms stable π-π stacking complexes with PDA, creating a versatile chemotherapeutic delivery platform. Biphasic calcium phosphate (BCP), whose composition closely resembles natural bone mineral, exhibits excellent biocompatibility and tunable bioactivity through phase ratio modulation. While 3D-printed BCP scaffolds offer precise geometric control, their inherent osteoinductive potential remains suboptimal. Integration of bone morphogenetic protein-2 (BMP2) through surface biofunctionalization represents a promising strategy to enhance scaffold bioactivity, though conventional BMP2 delivery systems suffer from initial burst release and dose-dependent complications. Heparin/polyethyleneimine (PEI) nanogels provide an elegant solution through BMP2 encapsulation, enabling sustained release kinetics and reduced systemic toxicity. This study proposes the development of a multifunctional scaffold system for synergistic chemo-photothermal therapy and bone regeneration in OS treatment. The design incorporates a DOX-conjugated PDA coating to anchor BMP2-loaded nanogels onto BCP scaffolds, achieving spatially controlled drug delivery and localized hyperthermia. We hypothesize that this integrated approach will demonstrate enhanced antitumor efficacy while promoting functional bone reconstruction. Comprehensive in vitro evaluations will elucidate the underlying mechanisms and provide preclinical validation for this precision oncology strategy.