Unified bilayer membranes with mechanically reinforced interface for stage-adaptive bone regeneration

Abstract

Abstract Guided bone regeneration using double-layered membranes is often hindered by poor interfacial integration, insufficient stability, and limited adaptability to regulate the complex healing process. Herein, we develop a unified bilayer membrane featuring a reinforced dual-crosslinking interface between barrier and porous layers through a homogeneous isomeric in-situ fabrication strategy. Its superior mechanical strength (~156 MPa in dry state and ~8.6 MPa in wet state) ensures the long-term degradation stability and bioactivity in vivo. Combined with sequentially released bioactive components, we show that the unified bilayer membrane regulates antibacterial functions, immunomodulation, neurovascularization, and osteogenesis, thereby enabling stage-adaptive bone regeneration. We test in a rat critical-sized cranial defect model to demonstrate that the membrane significantly outperforms the clinical collagen membrane, achieving ~2.7-fold greater bone volume regeneration after 8 weeks. This work further elucidates the spatiotemporal osteogenic mechanisms of the unified bilayer membrane, which constructs a well-integrated regenerative microenvironment and promotes a tightly interconnected neurovascular-osteogenic communication network during stage-adaptive bone repair.