Combinatorial Assembly of Biomimetic Janus Membrane with Multiscale Architectures for Guided Bone Regeneration

ABSTRACT Guided bone regeneration (GBR) has gained significant attention in the field of bone tissue engineering. However, designing an effective barrier membrane that simultaneously meets the mechanical and biological requirements at the soft–hard tissue interface remains a considerable challenge. Herein, we introduce a combinatorial assembly strategy to construct a continuous Janus membrane with multiscale architectural features inspired by biological materials. Structurally, the membrane features an asymmetric design, comprising a compact layer with a Bouligand architecture that incorporates amorphous calcium phosphate (ACP) to enhance mechanical strength and prevent soft tissue infiltration, and a porous layer that recapitulates the trabecular structure of cancellous bone, enriched with hydroxyapatite (HAp) crystals to promote cellular adhesion and osteoinduction. Subsequent in vitro and in vivo results show that the membrane not only exhibits excellent biocompatibility and barrier function but also significantly enhances osteogenic differentiation and bone regeneration in a cranial defect model. This work demonstrates that integrating diverse fabrication techniques enables the creation of functionally efficient GBR membranes with hierarchical structures, offering a promising pathway toward multifunctional regenerative materials.