Periosteum-bone inspired hierarchical scaffold with endogenous piezoelectricity for neuro-vascularized bone regeneration
Yao Zhao, Yun-Fan Cai, Wenkai Wang, Yongkang Bai, Mingyi Liu, Y. Wang, Wen Niu, Zhixiao Luo, Lingyun Xia, Juanfang Zhu, Fei Zhao, Franklin R. Tay, Li‐na Niu
Abstract
The development of scaffolds for repairing critical-sized bone defects heavily relies on establishing a neuro-vascularized network for proper penetration of nerves and blood vessels. Despite significant advancements in using artificial bone-like scaffolds infused with various agents, challenges remain. Natural bone tissue consists of a porous bone matrix surrounded by a neuro-vascularized periosteum, with unique piezoelectric properties essential for bone growth. Drawing inspiration from this assembly, we developed a periosteum-bone-mimicking bilayer scaffold with piezoelectric properties for regeneration of critical-sized bone defects. The periosteum-like layer of this scaffold features a double network hydrogel composed of chelated alginate, gelatin methacrylate, and sintered whitlockite nanoparticles, emulating the viscoelastic and piezoelectric properties of the natural periosteum. The bone-like layer is composed of a porous structure of chitosan and bioactive hydroxyapatite created through a biomineralization process. Unlike conventional bone-like scaffolds, this bioinspired bilayer scaffold significantly enhances osteogenesis, angiogenesis, and neurogenesis combined with low-intensity pulsed ultrasound-assisted piezoelectric stimulation. Such a scheme enhances neuro-vascularized bone regeneration in vivo . The results suggest that the bilayer scaffold could serve as an effective self-powered electrical stimulator to expedite bone regeneration under dynamic physical stimulation. Inadequate neuro-vascularization presents a significant hurdle in treating critical-sized bone defects. The periosteum, acknowledged for its distinct piezoelectric nature and abundant neuro-vascular networks, is integral to osteogenesis. Inspired by natural bone tissue, we introduce a novel bone implant emulating periosteum-bone architecture and integrating unique piezoelectric properties. This innovative strategy targets neuro-vascularized bone regeneration. • A novel bone scaffold is prepared by emulating periosteum-bone features. • The viscoelastic and piezoelectricity of the periosteum-bone interface are well emulated. • Bone-like layer is of 3D porous structure and in-situ biomineralized hydroxyapatite. • Boosting osteogenesis by piezoelectricity and Mg 2+ of the periosteum-mimicking hydrogel. • The bioinspired scaffold enhanced neuro-vascularized bone regeneration.