Bone regeneration is clinically challenging because vascularization, osteo-induction, and immune modulation are difficult to synchronize. Inspired by the native periosteum's bilayer architecture and multifunctional roles, we developed a wood-engineered Janus periosteum (EW-P-D@HACA-T) that integrates deferoxamine (DFO)-functionalized elastic wood (EW-P-D) with a bio-adhesive catechol-modified hyaluronic acid/tricalcium phosphate hydrogel (HACA-T). This construct mimics the anisotropic structure and compartmentalized functions of natural periosteum, providing dual support for angiogenesis and osteo-immunomodulation. EW-P-D maintains mechanical integrity and guides cell orientation, while sustained release activates the HIF-1α/VEGF pathway to enhance endothelial maturation and bone formation. Concurrently, the HACA-T composite hydrogel promotes osteogenic differentiation and polarizes macrophages toward an M2 phenotype, creating a pro-regenerative immune microenvironment. Furthermore, transcriptomic profiling revealed coordinated activation of p53, TGF-β, and ECM remodeling pathways, highlighting the scaffold's capacity to orchestrate tissue regeneration at the molecular level. In vivo evaluation using a rat skull defect model confirmed superior bone bridging, collagen deposition, neovascularization, and systemic biosafety. This study presents a structurally and functionally integrated wood-engineered periosteum substitute, demonstrating a paradigm shift toward engineered solutions that synchronize mechanical, angiogenic, and immunomodulatory cues for bone defect repair.
Yuhe Yang,Tianpeng Xu,Ho Pan Bei,Yuanjin Zhao,Xin Zhao
Existing artificial periostea faces difficulty in supporting the entire bone repair cycle due to the absence of adhesion-centric design and effective cell manipulation, leading to poor inhibition of soft tissue infiltration and induction of osteogenesis and angiogenesis. Here, a Janus periosteum with interior surface adhesion and exterior anatomical patterns to mimic the structure and function of natural periosteum is presented. Photo-crosslinkable polymers are employed to replicate the exterior anisotropic surface structured microgrooves for cell fate manipulation and assemble gecko-inspired fibrillar setae arrays for interior surface adhesion. To further bolster its underwater adhesiveness, mussel-inspired poly (dopamine methacrylamide-co-hydroxyethyl methacrylate) (PDMH) is coated onto the periosteum surfaces. This periosteum presents adhesiveness with strong shear and normal adhesion in both dry and wet conditions due to the coordinated interactions of micro setae arrays and PDMH coating; it also boasts effective cell modulation for enhanced synchronous osteogenesis and angiogenesis, without the aid of growth factors. Moreover, the Janus periosteum is found to enhance bone regeneration in vivo with increased new bone formation and neovascularization. It is envisioned that this Janus periosteum will be able to streamline bone fracture surgical repair as a rapidly adhesive, low-maintenance yet robust bandage to significantly cut down the healing phase.
危险品化学品经营许可证（带存储）