Synergistic enhancement of bone regeneration by obacunone-loaded peg-based composite scaffolds

In this study, we report the design and fabrication of a novel biomimetic composite scaffold (PSGO) and systematically assess its potential for bone tissue engineering. The PSGO scaffold was fabricated using three-dimensional (3D) printing technology with a base matrix composed of polyethylene glycol (PEG), sodium alginate (SA), and gelatin (GEL). Obacunone-loaded polycaprolactone (OA@PM) microspheres were embedded within the scaffold to enable sustained drug release, thereby creating a structure with precise architecture and functional gradients. Comprehensive characterization of the scaffold's surface morphology, rheological properties, and drug release behavior was performed. In vitro experiments demonstrated that the PSGO scaffold significantly promoted the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs), enhanced the expression of key osteogenic markers (RUNX-2 and OCN), and facilitated mineralized matrix formation. Furthermore, in vivo evaluation using a rat calvarial critical-size defect model-assessed via micro-computed tomography and histological analysis-confirmed its excellent osteogenic performance, with substantial new bone formation observed at both the defect margins and center. With its outstanding biocompatibility, osteoinductive capabilities, and controlled drug release properties, the PSGO scaffold offers a promising new approach for the clinical repair of large-scale bone defects.