Dopamine-Functionalized Osteon-Mimetic Polycaprolactone/β-Tricalcium phosphate Membranes: Antibacterial Efficacy and MAPK/p53-Mediated Osteohomeostasis

Abstract

Treating infected alveolar bone defects represents a clinical challenge, requiring strategies that concurrently eradicate pathogens and restore homeostatic bone remodeling. Herein, we engineered an osteon-mimetic guided-bone-regeneration (GBR) membrane by integrating β-tricalcium phosphate (β-TCP) into a polycaprolactone (PCL) membrane with a concentric microgrooved topography, functionalized via dopamine (DOPA) coating. The DOPA modification enhanced hydrophilicity and nanoscale roughness, enabling sustained 8-week Ca2+ release. Furthermore, the microgroove and DOPA synergy moderately accelerated degradation while preserving robust mechanical properties and physiological pH. Systematic optimization identified the 24-hour DOPA-coated variant (24DOPA@M-PCL/β-TCP) as the optimal formulation. This membrane exhibited potent antibacterial efficacy against S. aureus and P. gingivalis, driven by sustained H2O2 generation during DOPA oxidation. Concurrently, it promoted osteogenic differentiation while suppressing osteoclastogenesis in vitro and exhibited excellent barrier function against gingival fibroblast infiltration. In vivo evaluations in a rat calvarial defect model demonstrated that 24DOPA@M-PCL/β-TCP facilitated superior bone regeneration, characterized by elevated osteocalcin/osteopontin expression and reduced TRAP-positive osteoclast recruitment. Transcriptomic and western blot analyses revealed that this dual-functional membrane modulates the bone microenvironment by activating the MAPK pathway while downregulating the p53 pathway. Our findings underscore the significant clinical translational potential of this biomimetic, dual-functional GBR membrane for managing infected bone defects.