H₂-driven autonomous pore-forming hydrogel promotes rapid vascularization for dry socket healing.

Abstract

Dry socket (DS) is a stomatological complication after tooth removal when the blood clot gets dislodged. The delayed healing of DS presents a major clinical challenge, primarily because of the angiogenesis impairment. To address this limitation, we developed a dynamic hydrogel hosting functional magnesium microspheres (Mg/Gel) which initiate autonomous, directional and sustained hydrogen (H₂) generation leading to the formation of hierarchical pores for vascularization. Beyond its role in providing physical support for vessel ingrowth, we found that Mg/Gel secures its localized and sustained H₂ release due to strong bioadhesion to both gingiva and alveolar bone. The released H₂ attenuates inflammation by regulating macrophage polarization through NF-κB signaling pathway and activates NRF2 to stabilize HIF-1α to promote angiogenesis in both in vitro and in vivo studies. Notably, DS implantation models revealed that Mg/Gel mitigates excessive inflammation responses in the early DS healing stage and enhances angiogenesis in the proliferative stage, thereby facilitating alveolar bone regeneration. These data suggest that our H₂-releasing Mg/Gel with self-assembling porous structure spatiotemporally coordinates the healing, thus offering a transformative strategy for DS treatment.