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载有消退素D1的甲基丙烯酸明胶在大鼠牙周炎模型中的应用

The Application of Resolvin D1-Loaded Gelatin Methacrylate in a Rat Periodontitis Model.

作者信息

Xing Zhe, Liu Jing, Cai Jiazheng, Jiang Xiaofeng, Liang Jingwen, Fujio Masahito, Hadler-Olsen Elin, Wang Jing, Kantarci Alpdogan, Xue Ying

机构信息

School of Stomatology, Lanzhou University, Lanzhou 730000, China.

Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, Lanzhou University, Lanzhou 730000, China.

出版信息

Pharmaceutics. 2024 Dec 25;17(1):16. doi: 10.3390/pharmaceutics17010016.

DOI:10.3390/pharmaceutics17010016
PMID:39861667
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11768520/
Abstract

To evaluate the drug release, cytocompatibility with periodontal ligament cells (PDLCs), and therapeutic efficacy of GelMA hydrogel loaded with resolvin D1 (RvD1) in treating rat periodontal inflammation and alveolar bone damage. An RvD1 complexed with GelMA was prepared, and its release kinetics and compatibility with PDLCs were assessed. Rats with induced periodontitis were treated weekly with topical applications of vehicle, GelMA, RvD1, or RvD1 complexed with GelMA for four weeks. Periodontal inflammation and tissue regeneration were evaluated using quantitative PCR (qPCR) and histochemical staining, while alveolar bone repair and regeneration were analyzed through micro-CT. The RvD1 complexed with GelMA effectively released RvD1 and enhanced the proliferation and viability of PDLCs. Compared to RvD1 alone, treatment with RvD1 complexed with GelMA significantly reduced inflammatory cell infiltration, TNF-α and RANKL expression, and osteoclast formation in periodontal tissues. Additionally, it promoted the expression of specific anti-inflammatory and regenerative markers. Micro-CT analysis confirmed significant new bone formation in the RvD1 complexed with GelMA-treated group. RvD1 complexed with GelMA provides sustained drug release and biocompatibility, effectively resolves periodontal inflammation, and promotes tissue regeneration in periodontitis.

摘要

为评估负载消退素D1(RvD1)的甲基丙烯酰化明胶(GelMA)水凝胶在治疗大鼠牙周炎和牙槽骨损伤中的药物释放、与牙周膜细胞(PDLCs)的细胞相容性及治疗效果。制备了RvD1与GelMA的复合物,并评估其释放动力学及与PDLCs的相容性。对诱导性牙周炎大鼠每周局部应用赋形剂、GelMA、RvD1或RvD1与GelMA的复合物,持续四周。使用定量聚合酶链反应(qPCR)和组织化学染色评估牙周炎症和组织再生,通过显微CT分析牙槽骨修复和再生情况。RvD1与GelMA的复合物有效释放RvD1并增强了PDLCs的增殖和活力。与单独使用RvD1相比,用RvD1与GelMA的复合物治疗可显著减少牙周组织中的炎性细胞浸润、肿瘤坏死因子-α(TNF-α)和核因子κB受体活化因子配体(RANKL)表达以及破骨细胞形成。此外,它还促进了特异性抗炎和再生标志物的表达。显微CT分析证实,RvD1与GelMA复合物治疗组有显著的新骨形成。RvD1与GelMA的复合物具有持续药物释放和生物相容性,能有效解决牙周炎症并促进牙周炎中的组织再生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/6e87a83a3fcf/pharmaceutics-17-00016-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/dc33cb4e021e/pharmaceutics-17-00016-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/52e067bf1519/pharmaceutics-17-00016-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/c60b5b262925/pharmaceutics-17-00016-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/a3fdad236a42/pharmaceutics-17-00016-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/121b49c66c46/pharmaceutics-17-00016-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/6e87a83a3fcf/pharmaceutics-17-00016-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/dc33cb4e021e/pharmaceutics-17-00016-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/52e067bf1519/pharmaceutics-17-00016-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/c60b5b262925/pharmaceutics-17-00016-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/a3fdad236a42/pharmaceutics-17-00016-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/121b49c66c46/pharmaceutics-17-00016-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142d/11768520/6e87a83a3fcf/pharmaceutics-17-00016-g006.jpg

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本文引用的文献

1
Immunomodulatory Biomaterials: Tailoring Surface Properties to Mitigate Foreign Body Reaction and Enhance Tissue Regeneration.免疫调节生物材料:通过调整表面特性来减轻异物反应并促进组织再生。
Adv Healthc Mater. 2024 Nov;13(29):e2401253. doi: 10.1002/adhm.202401253. Epub 2024 Oct 6.
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Salivary matrix metalloproteinase-9 (MMP-9) as a biomarker of periodontitis in pregnant patients with diabetes.唾液基质金属蛋白酶-9(MMP-9)作为糖尿病孕妇牙周炎的生物标志物。
Dent Med Probl. 2023 Jan-Mar;60(1):35-45. doi: 10.17219/dmp/147104.
3
Resolvin D1 improves allograft osteointegration and directly enhances osteoblasts differentiation.
解析度蛋白 D1 可促进移植物骨整合,并直接促进成骨细胞分化。
Front Immunol. 2023 Feb 27;14:1086930. doi: 10.3389/fimmu.2023.1086930. eCollection 2023.
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Host and bacterial factors linking periodontitis and rheumatoid arthritis.牙周炎和类风湿性关节炎相关的宿主和细菌因素。
Front Immunol. 2022 Aug 25;13:980805. doi: 10.3389/fimmu.2022.980805. eCollection 2022.
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The effect of resolvin D1 on bone regeneration in a rat calvarial defect model.解析素 D1 对大鼠颅骨缺损模型中骨再生的影响。
J Tissue Eng Regen Med. 2022 Nov;16(11):987-997. doi: 10.1002/term.3345. Epub 2022 Aug 18.
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Impact of Resolvin D1 on the inflammatory phenotype of periodontal ligament cell response to hypoxia.解析素 D1 对牙周膜细胞缺氧反应炎症表型的影响。
J Periodontal Res. 2022 Oct;57(5):1034-1042. doi: 10.1111/jre.13044. Epub 2022 Aug 9.
7
Effects of immune cells on mesenchymal stem cells during fracture healing.骨折愈合过程中免疫细胞对间充质干细胞的影响。
World J Stem Cells. 2021 Nov 26;13(11):1667-1695. doi: 10.4252/wjsc.v13.i11.1667.
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Synergistic antibacterial activity of herbal extracts with antibiotics on bacteria responsible for periodontitis.草药提取物与抗生素对引起牙周炎的细菌的协同抗菌活性。
J Infect Dev Ctries. 2021 Nov 30;15(11):1685-1693. doi: 10.3855/jidc.14904.
9
RvD1 accelerates the resolution of inflammation by promoting apoptosis of the recruited macrophages via the ALX/FasL-FasR/caspase-3 signaling pathway.RvD1通过ALX/FasL-FasR/半胱天冬酶-3信号通路促进募集的巨噬细胞凋亡,从而加速炎症消退。
Cell Death Discov. 2021 Nov 8;7(1):339. doi: 10.1038/s41420-021-00708-5.
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Mater Sci Eng C Mater Biol Appl. 2021 Oct;129:112393. doi: 10.1016/j.msec.2021.112393. Epub 2021 Aug 25.