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甲基丙烯酰化明胶@MP196/外泌体水凝胶诱导中性粒细胞凋亡和巨噬细胞M2极化以抑制牙周骨丧失。

Gelatin methacryloyl @MP196/exos hydrogel induced neutrophil apoptosis and macrophage M2 polarization to inhibit periodontal bone loss.

作者信息

Zhuo Haiwei, Zhang Shuting, Wang Hongbo, Deng Jiayin, Zhang Xi

机构信息

Department of Periodontology, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, No.12 Qixiangtai Road, Heping District, Tianjin 300070, PR China; Tianjin Medical University Institute of Stomatology, No.12 Qixiangtai Road, Heping District, Tianjin 300070, PR China.

Department of Periodontology, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, No.12 Qixiangtai Road, Heping District, Tianjin 300070, PR China; Tianjin Medical University Institute of Stomatology, No.12 Qixiangtai Road, Heping District, Tianjin 300070, PR China.

出版信息

Colloids Surf B Biointerfaces. 2025 Apr;248:114466. doi: 10.1016/j.colsurfb.2024.114466. Epub 2024 Dec 21.

Abstract

OBJECTIVES

Periodontitis is an inflammatory and destructive disease caused by dental plaque, which can result in the immune microenvironment disorders and loss of periodontal support tissue. In order to promote the restoration of local microenvironment stability, a functional biomaterial Gelatin methacryloyl @MP196/exos based on characteristics of disease occurrence is designed.

METHODS

Transmission electron microscopy, nanosight particle tracking analysis and western blot analysis were applied to prove the presence of exos in GelMA@MP196/exos. The swelling and degradation rates of GelMA@MP196/exos were evaluated. Cell proliferation, antibacterial ability and cellular uptake and intracellular internalization of exos were assessed in the study. Efferocytosis and M2 polarization of macrophages was estimated and the effects of GelMA@MP196/exos were proved in vivo.

RESULTS

GelMA@MP196/exos upregulated the expression of genes and proteins related to neutrophil apoptosis and promoted neutrophil apoptosis, macrophage M2 polarization, and efferocytosis. Furthermore, GelMA@MP196/exos exhibited significant antibacterial activity against Streptococcus gordonii, Fusobacterium nucleatum, and Porphyromonas gingivalis. GelMA@MP196/exos alleviated periodontitis and reduced alveolar bone loss in vivo in rat models.

CONCLUSIONS

GelMA@MP196/exos can serve as a potential strategy for the treatment of periodontitis.

CLINICAL SIGNIFICANCE

The main aim of periodontal therapy is to remove dental plaque and eliminate inflammation. However, some patients with low plaque scores and insufficient neutrophil clearance, resulting in poor responsiveness to periodontal therapy. Under the circumstances, local Application of drug that regulate the immune microenvironment had significance in controlling the progression of inflammation.

摘要

目的

牙周炎是一种由牙菌斑引起的炎症性破坏性疾病,可导致免疫微环境紊乱和牙周支持组织丧失。为促进局部微环境稳定性的恢复,基于疾病发生特点设计了一种功能性生物材料明胶甲基丙烯酰基@MP196/外泌体。

方法

应用透射电子显微镜、纳米可视颗粒追踪分析和蛋白质免疫印迹分析来证明外泌体存在于明胶甲基丙烯酰基@MP196/外泌体中。评估了明胶甲基丙烯酰基@MP196/外泌体的溶胀率和降解率。在本研究中评估了细胞增殖、抗菌能力以及外泌体的细胞摄取和细胞内内化情况。评估了巨噬细胞的噬菌作用和M2极化,并在体内证明了明胶甲基丙烯酰基@MP196/外泌体的作用。

结果

明胶甲基丙烯酰基@MP196/外泌体上调了与中性粒细胞凋亡相关的基因和蛋白质的表达,并促进了中性粒细胞凋亡、巨噬细胞M2极化和噬菌作用。此外,明胶甲基丙烯酰基@MP196/外泌体对戈登链球菌、具核梭杆菌和牙龈卟啉单胞菌表现出显著的抗菌活性。在大鼠模型体内,明胶甲基丙烯酰基@MP196/外泌体减轻了牙周炎并减少了牙槽骨吸收。

结论

明胶甲基丙烯酰基@MP196/外泌体可作为治疗牙周炎的一种潜在策略。

临床意义

牙周治疗的主要目的是清除牙菌斑和消除炎症。然而,一些患者牙菌斑评分低且中性粒细胞清除不足,导致对牙周治疗反应不佳。在这种情况下,局部应用调节免疫微环境的药物对控制炎症进展具有重要意义。

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