Abstract
Segmental bone defects are large, non-healing injuries characterized by insufficient structural support and limited bioactivity, posing a significant clinical challenge. In this study, we developed biomimetic chitosan/polyvinyl alcohol-glycerol (CS/PG) scaffolds inspired by porcupine quills, which were fabricated via fused deposition modeling and unidirectional freeze casting. The as-prepared scaffold featured a dense outer layer of polyvinyl alcohol-glycerol (PG) with high compressive strength (24.21 ± 0.11 MPa at 25% strain) and an oriented inner foam of chitosan (CS). The CS foam was further incorporated with poly (3,4-ethylenedioxythiophene) polystyrene sulfonic acid (PEDOT:PSS, denoted as PP) and amorphous zinc phosphate (AZP) to form PP-AZP-CS/PG, aimed at enhancing neural conductivity and stimulating blood vessel formation, respectively. The in vitro results indicated that the biomimetic scaffolds exhibited excellent biocompatibility while significantly enhancing angiogenesis and osteogenesis capabilities. In a rabbit radial segmental defect model, PP-AZP-CS/PG achieved robust bone regeneration, attaining a bone volume/total volume of approximately 26.22% after implantation for 8 weeks. Overall, this biomimetic scaffold demonstrated that integrating hierarchical design with additional bioactive components enhanced mechanical support while promoting new bone regeneration, addressing critical challenges in segmental bone defect repair.