Synergetic regulation of osteoimmune microenvironment and osteogenesis by decellularized amnion membrane for guided bone regeneration

Immunoregulatory properties of guided bone regeneration (GBR) membranes are essential for modulating the osteoimmune microenvironment to enhance osteogenesis. Decellularized amnion membrane (DAM), an extracellular matrix material derived from the placenta through the removal of cells and antigenic components, has attracted attention due to its low immunogenicity and rich composition. This study investigated the role of DAM in modulating the immune microenvironment, its impact on osteogenesis, and associated mechanisms during the GBR process. DAM exhibited high biocompatibility and directly promoted osteogenesis in vitro. Furthermore, DAM induced macrophage M2 polarization, mitigated oxidative stress under inflammatory contexts, and optimized the immune microenvironment, thereby indirectly enhancing cell migration and osteogenic differentiation. Multi-omics analysis revealed a crucial role of the PI3K-Akt signaling pathway, coordinated with immune-related TLR and TNF signaling pathways, in this process-highlighting the potential applications of DAM in the treatment of inflammatory bone defects. DAM's abundant bioactive components and distinctive three-dimensional architecture enable this synergistic effect. In vivo, DAM effectively inhibited inflammation and accelerated bone regeneration in a rat model of critical-size cranial defects. This study demonstrates that DAM possesses strong osteoimmunomodulatory properties and elucidates its underlying mechanisms in bone regeneration, making it a promising GBR membrane for clinical applications.