Dual functional properties of a probiotic biofilm-decorated bone substitute to combat infection and promote osteoimmunomodulation

Oral and maxillofacial bone defects are prevalent and challenging to treat, often leading to significant complications such as infection and impaired healing. Enhancing the antibacterial and osteoimmunomodulatory properties of bone graft materials represents a promising approach to improve regenerative outcomes. In this study, we developed a hydroxyapatite scaffold coated with a biofilm of the probiotic <i>Akkermansia muciniphila</i> (<i>Akk</i>-HA), engineered to simultaneously combat infection and modulate the immune environment. <i>Akk</i>-HA exhibited vigorous anti-adhesive activity against pathogenic bacteria and attenuated inflammatory responses by suppressing proinflammatory cytokine secretion while promoting the release of proregenerative mediators from macrophages. Mechanistic studies revealed that <i>Akk</i>-HA activated the PI3K/AKT signalling pathway, leading to the upregulation of interleukin-10 (IL-10), in turn enhancing the osteogenic differentiation of periodontal ligament cells (PDLCs). In a murine model of infected periodontal bone defects, <i>Akk</i>-HA demonstrated significant antibacterial and immunomodulatory effects, resulting in markedly improved bone regeneration. These findings highlight the therapeutic potential of probiotic-functionalized bone grafts as a dual-action strategy for managing infected bone defects in the oral and maxillofacial regions.