Synergistic bone regeneration via dual growth factor-loaded chitosan/anorganic bovine xenograft scaffolds with different pore structures

• Dual-porosity C/ABX scaffolds provide optimal architecture for bone regeneration. • Sustained co-delivery of BMP-7 and PDGF enhances osteogenesis and angiogenesis. • hDPSC proliferation and differentiation significantly improved on dual-factor scaffolds. • Rat calvarial model confirmed superior bone volume and vascularized bone formation. • Scaffold integrates structure, mechanics, and biology into a synergistic design strategy. Critical-size bone defects in the oral and maxillofacial regions present significant clinical challenges due to their limited healing capacity. This study investigates the combined regenerative potential of a chitosan/anorganic bovine xenograft (C/ABX) scaffold incorporating platelet-derived growth factor-BB (PDGF) and bone morphogenetic protein-7 (BMP-7). The C/ABX/BMP-7/PDGF scaffold exhibited an interconnected porous structure and a sustained, biphasic release profile of growth factors. This scaffold demonstrated excellent biocompatibility and significantly enhanced the proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs) in vitro, leading to the upregulation of key genes such as RUNX2, OCN, OPN, and COL1. In a rat calvarial defect model, the dual-factor scaffold, particularly when seeded with hDPSCs, markedly promoted new bone formation and vascular development compared to other experimental groups. This was evidenced by increased bone volume, trabecular thickness, and heightened expression of angiogenic (CD31) and osteogenic (OPN) markers. These findings highlight the potent synergistic effect of BMP-7 and PDGF within biomimetic scaffolds, providing a promising, multifaceted strategy for the clinical management of oral and maxillofacial bone defects.