Multi-biomimetic poly(amino acid)-based Janus membrane integrating barrier and osteoinductive functions for cranial bone regeneration

Guided bone regeneration (GBR) membranes play a critical role in repairing bone defects, yet conventional collagen-based membranes suffer from immunogenicity, insufficient mechanical strength, and lack of osteoinductivity. Herein, a multi-biomimetic poly(γ-benzyl-L-glutamate) (PBLG)-based Janus membrane (PP-S/MH-P) is constructed that integrates a robust barrier function with potent osteoinductive capacity. The membrane is fabricated with a Janus architecture: PP-S side consists of a dense poly(γ-benzyl-L-glutamate) (PBLG) barrier layer, physically blended with PEGDA and surface-grafted with zwitterionic poly(sulfobetaine methacrylate) (PSBMA) brushes, the opposite MH-P side comprises Mg-doped hydroxyapatite surface-grafted with PBLG, forming a bone-mimetic nanofibrous network. The membrane exhibits robust mechanical properties (tensile strength: 5.42 MPa; elastic modulus: 141.72 MPa), favorable wet tissue conformability, and enzymatic degradation. The PP-S side effectively resists bacterial ( E. coli and S. aureus ) invasion and fibroblast adhesion; while the MH-P side enables sustained Mg 2+ release, significantly promotes rBMSCs spreading, mineralization, and upregulation of osteogenic genes (RUNX2, ALPL, OCN). In a rat calvarial defect model, PP-S/MH-P membrane prevents soft-tissue infiltration and achieves outstanding new bone formation, with BV/TV reaching 86.13 ± 7.61% at 12 weeks. This multi-biomimetic Janus membrane, combining compositional, structural, and functional biomimicry, offers a promising strategy for designing high-performance GBR membranes with simultaneous barrier protection and osteogenic promotion.