Bioengineered functional scaffolds co-loaded with osteonectin and HA-internalizing osteoblasts for boosting bone regeneration

Traditional bone repair scaffolds often struggle to meet the demands of complex bone defect regeneration due to insufficient early osteogenic stimulation or osteogenesis. In this study, we proposed a synergistic strategy to combine PHA (PCL/HA) scaffolds with HA-internalized osteoblasts (OHA) and osteonectin (ON), where OHA provides fast calcium and phosphate ion release via lysosomal degradation, and ON facilitates calcium phosphate–collagen binding to jointly enhance the early bone regeneration. This “OHA + ON” dual-pathway synergy helps to overcome the limitations of poor early osteogenesis or insufficient Ca/P ion release. The results demonstrated that the PHA + ON+OHA combination was much superior to PHA or PHA + ON scaffolds in terms of the osteogenic gene expression, osteoblast proliferation and mineralization in vitro , and the osteogenic capability in subcutaneous model and femoral defect model in vivo . These findings suggest that the “OHA + ON” synergistic strategy realizes an early pro-osteogenesis, optimizes the osteogenic process, and elevates the new bone quality, offering a viable approach for future clinical repair of complex bone defects.