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基于抗菌和 DNA 的水凝胶原位阻断 TNF-α 以促进糖尿病牙槽骨重建。

Antibacterial and DNA-Based Hydrogels In Situ Block TNF-α to Promote Diabetic Alveolar Bone Rebuilding.

机构信息

Department of Endocrinology and Metabolism, Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China.

Department of Dermatology, West China Hospital, Sichuan University, Chengdu, 610041, China.

出版信息

Macromol Rapid Commun. 2024 Mar;45(5):e2300559. doi: 10.1002/marc.202300559. Epub 2024 Feb 2.

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, an antibacterial DNA-based hydrogel named Agantigel is developed by integrating silver nanoclusters (AgNCs) and tumor necrosis factor-alpha (TNF-α) 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-α antibody from Agantigel effectively blocks TNF-α 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-α (42.52 ± 15.85%). The results imply that DNA hydrogels are potential bio-scaffolds helping the sustained release of multidrug for treating DABI or other oral diseases.

摘要

糖尿病条件下的牙槽骨损伤会严重阻碍许多口腔疾病的治疗。由于持续的感染和炎症反应,目前临床上重建糖尿病牙槽骨具有挑战性。在这里,通过将银纳米簇 (AgNCs) 和肿瘤坏死因子-α (TNF-α) 抗体整合到 DNA 水凝胶中,开发了一种名为 Agantigel 的抗菌 DNA 水凝胶,以促进糖尿病牙槽骨再生。Agantigel 可以通过 AgNCs 有效抑制细菌生长,同时在体外表现出可忽略不计的细胞毒性。Agantigel 中 TNF-α 抗体的持续释放有效阻断了 TNF-α,促进了巨噬细胞的 M2 极化,最终在体内加速了糖尿病牙槽骨的再生。经过 21 天的治疗,Agantigel 可将糖尿病牙槽骨缺损的愈合率提高至 82.58±8.58%,与游离 TNF-α(42.52±15.85%)相比,改善了小梁结构。结果表明,DNA 水凝胶是一种潜在的生物支架,有助于多药物的持续释放,以治疗 DABI 或其他口腔疾病。

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