Commensal microbiota-coated biohybrid implants induce antibiofilm, osteogenic, and immunomodulatory responses in a human 3D immunocompetent model.

Medical devices have revolutionized patient care; however, their abiotic surfaces remain highly susceptible to bacterial biofilm formation, enabling immune evasion and antibiotic resistance. Although antibacterial coatings can mitigate bacterial colonization, many rely on antimicrobial agents that may drive resistance and often lack the capacity to actively modulate host immunity or promote osteogenesis. Here, we introduce innovative Commensal Hybrid Materials (CHMs), multifunctional implant interfaces generated by coating titanium with commensal microflora via a heat-anchoring inactivation process to create a safe, stable surface layer. Surface analyses (SEM/EDS, FTIR, Raman, XPS) confirmed a thick, near-hydrophobic coating with a polar biomolecular overlayer bearing protein (amide), lipid (C-H), and phosphate/phosphoryl signatures. CHMs were non-haemolytic, biocompatible with human cells, enhanced macrophage antimicrobial activity by increasing reactive oxygen species production while maintaining balanced phagocytosis, and reduced biofilm formation by the periodontal pathogen Porphyromonas gingivalis. CHMs induced balanced macrophage polarization and osteoimmunomodulation, increasing expressions of IL-1β, TNF-α (M1), IL-10 (M2), and the osteoinductive mediator oncostatin M (OSM), while significantly upregulating RUNX2 in co-cultured periodontal ligament stem cells with an early, self-limiting cytokine profile. In a clinically relevant human immunocompetent three-dimensional implant-tissue-oral-bacterial-biofilm (INTERbACT) model integrating fibroblasts, epithelial cells, macrophages, and multispecies biofilms, CHMs preserved epithelial integrity under dysbiotic challenge and significantly reduced biofilm volume while tuning macrophages toward both antimicrobial (M1) and reparative (M2) states. CHMs also reduced pro-inflammatory cytokine expression under both sterile and biofilm-exposed conditions. Collectively, CHMs uniquely combine biofilm resistance, immune-mediated clearance, and osteogenic stimulation, supporting translation to dental and orthopaedic implants.