Engineering a vascularized-osteogenic microenvironment to enhance bone regeneration via a 3D-printed composite scaffold with progressive-release bio-factors

BACKGROUND: Critical-sized bone defects remain challenging to repair because successful regeneration requires both mechanical stability and the coordinated promotion of osteogenesis and vascularization. To address these needs, we developed a composite scaffold (GV@PHL) that integrates structural support with sustained pro-angiogenic signaling. METHODS: A 3D-printed framework composed of polycaprolactone (PCL), nano-hydroxyapatite (nano-HA), and Laponite (PHL) was fabricated to form an interconnected porous architecture with intrinsic osteogenic potential and printability. A GelMA hydrogel was photo-crosslinked within the scaffold pores and covalently tethered to vascular endothelial growth factor (VEGF) to create a photo-embedded GelMA–VEGF phase, enabling sustained VEGF release. The composite scaffold (GV@PHL) was evaluated through in vitro and in vivo experiments to assess architecture stability, osteogenic differentiation, VEGF release behavior, endothelial cell responses, and vascularization. RESULTS: The GV@PHL scaffold maintained a stable porous architecture and exhibited synergistic performance combining structural integrity with biological activity. The PHL framework supported osteogenic differentiation, while the photo-crosslinked GelMA–VEGF hydrogel enabled controlled, sustained release of VEGF. Released VEGF promoted endothelial cell survival and enhanced vascularization in vitro and in vivo, demonstrating coordinated support for osteogenesis and angiogenesis. CONCLUSIONS: GV@PHL represents a practical strategy for integrating structural design and biological function in bone tissue engineering. By combining a mechanically stable, osteoinductive 3D-printed framework with sustained VEGF delivery to promote vascularization, this platform shows promise for treating critical-sized craniofacial and orthopedic bone defects.