Antibacterial and DNA-based hydrogels in situ block TNF-alpha to promote diabetic alveolar bone rebuilding

Abstract

Alveolar bone injury under diabetic conditions can severely impede many oral disease treatments. Rebuilding diabetic alveolar bone in clinics is currently challenging due to persistent infection and inflammatory response. Here, we develop an antibacterial DNA-based hydrogel named Agantigel by integrating silver nanoclusters (AgNCs) and tumor necrosis factor-alpha (TNF-alpha) antibody into DNA hydrogel to promote diabetic alveolar bone regeneration. Agantigel can effectively inhibit bacterial growth through AgNCs while exhibiting negligible cytotoxicity in vitro. The sustained release of TNF-alpha antibody from Agantigel effectively blocks TNF-alpha and promotes M2 polarization of macrophages, ultimately accelerating diabetic alveolar bone regeneration in vivo. After 21 days of treatment, Agantigel significantly accelerates the defect healing rate of diabetic alveolar bone up to 82.58 +/- 8.58% and improves trabecular architectures compared to free TNF-alpha (42.52 +/- 15.85%). Our results imply that DNA hydrogels are potential bio-scaffolds helping the sustained release of multidrug for treating DABI or other oral diseases.