Hierarchical Mineralized Collagen Coated Zn Membrane to Tailor Cell Microenvironment for Guided Bone Regeneration

Abstract Maxillofacial bone defects caused by trauma, infections, tumors, and congenital disorders have become a significant global health concern. An ideal guided bone regeneration (GBR) membrane is expected to not only act as a barrier but also promote osteoinduction and osteogenesis. However, non‐resorbable membranes have limited bioactivity and require secondary surgeries, whereas resorbable membranes often lack the required mechanical properties and degrade too quickly. To address these challenges, a bilayer self‐induced GBR membrane is constructed by combining pure zinc (Zn) and hierarchical mineralized collagen (HMC) via self‐assembly, termed ss‐HMC/Zn. The Zn layer acts as an outer barrier toward the soft tissue that provides spatiotemporal support, whereas the HMC layer creates a favorable internal self‐induced osteogenic microenvironment. Moreover, the bone‐like nanostructure of HMC effectively controlled the release of zinc ions. In vitro assays demonstrates adequate mechanical maintenance, excellent cytocompatibility, and osteogenic ability of the membrane. In vivo results show superior osteoinductive capability without the need for osteogenic supplements. Furthermore, the ss‐HMC/Zn membrane exhibits immunomodulatory functions, promoting angiogenesis and cell recruitment, thereby shedding light on the underlying osteogenic mechanisms. In conclusion, these well‐orchestrated membranes provide new insights into guided bone regeneration for maxillofacial bone defects.