An axolotl limb regeneration-inspired strategy to enhance alveolar bone regeneration

Guided bone regeneration (GBR) is widely applied in implant dentistry, employing barrier membranes to create an osteogenic space by preventing gingival tissue ingrowth. However, this method does not enhance the osteogenic capacity of osteoblasts, limiting sufficient bone volume in larger defects. Inspired by axolotl limb regeneration, abundant soft tissue-derived stem cells mobilized to the defect may facilitate comprehensive osteogenesis within a BMP-2-enriched environment. We developed a biomimetic channel system (BCS) to promote alveolar bone regeneration, using channel structures to activate gingival-derived stem cells under a BMP-2-enriched biological barrier. In a cell-tracing mouse model, Prrx1 + stem cells demonstrated a critical role in BMP-2-induced subcutaneous osteogenesis. Sequencing and histological analyses revealed that channel structures significantly enhance soft tissue cell proliferation and migration. Attributable to the biological barrier, BCS applications markedly improved bone formation in beagle mandibular defects. These results suggest a novel osteoinductive strategy for alveolar bone regeneration that functions without a traditional barrier membrane.