Biomimetic Self-Adhesive Artificial Periosteum with Micro/Nanofibrous Structure Accelerates Bone Reconstruction via Synergistic Osteogenesis and Angiogenesis

Abstract

Critical-sized bone defects remain a major clinical challenge, and the periosteum, comprising a highly vascularized outer fibrous layer and an osteogenic inner layer, is crucial for bone repair. Herein, a biomimetic bilayer artificial periosteum (CP-HP) was developed, consisting of a hierarchically aligned micro/nanofibrous polycaprolactone-chitosan (PCL-CS) outer layer and an adhesive hydroxyapatite-polydopamine-polyacrylamide (HA–PDA-PAM) hydrogel inner layer. The fibrous outer layer provided aligned topographical cues and a mechanical barrier, which promoted angiogenesis, modulated the immune microenvironment, and prevented soft tissue invasion, while the hydrogel inner layer offered strong tissue adhesion and a mineralized microenvironment that stabilized the implant and facilitated osteogenesis. In vitro results demonstrated that the outer fibrous layer significantly enhanced adhesion, spreading, proliferation, and migration of HUVECs, accompanied by upregulated expression of integrin β1 and vinculin, indicating pronounced pro-angiogenic potential. Meanwhile, the bilayer periosteum promoted proliferation and osteogenic differentiation of MC3T3-E1 cells, as evidenced by increased ALP activity and elevated expression of osteogenic markers (ALP, Runx2, Col-I, and OCN). In vivo subcutaneous and cranial defect implantation further confirmed enhanced angiogenesis, improved immune regulation, and robust bone regeneration. Overall, CP-HP effectively mimicked the native periosteum’s dual-layer regenerative mechanism and synergistically promoted angiogenesis and osteogenesis, providing a promising strategy for repairing critical-sized bone defects.