Antibacterial collagen-based heterogeneous bilayer barrier membrane for guiding bacteria-infected bone defects regeneration

Pathogenic bacteria associated infection is a major cause of guided bone regeneration (GBR) treatment failure clinically. Antibacterial GBR membranes are promising strategies for addressing bacterial infection risk in bone repair. Here, an antibacterial heterogeneous bilayer collagen-based membrane (CDCP) was fabricated by controlling the crosslinking density between collagen and dialdehyde carboxymethyl cellulose (DCMC), which was composed of a porous layer containing nano-hydroxyapatite (nHap) to mimic bone's organic-inorganic composition, and a dense layer loading with chlorhexidine-carrying nanoparticles (CHX@mPDA NPs) to endow membrane with sustained antibacterial activity. CDCP membrane demonstrated good hemostasis and osteoblast/fibroblast cytocompatibility, besides drastically improved mechanical strength and biodegradation stability. CDCP membrane possessed robust broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria due to the sustained release of antibacterial drug CHX. CDCP membrane with dense network structure had strong physical barrier function against the inward growth of L929 cells, while the loose porous layer demonstrated significant induction in osteogenic differentiation of BMSCs. CDCP membrane had a significant promoting effect in bacteria-infected bone repair based on the synergistic effects of its powerful in vivo antibacterial activity and unique heterogeneous bilayer structure. Overall, CDCP membrane held potential application value and broad development prospects in the field of bacteria-infected bone repair.