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

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.