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抑菌聚(L-丙交酯-共-乙交酯)/聚(L-丙交酯-共-ε-己内酯)静电纺丝膜对进展期牙周炎牙槽骨缺损的综合修复作用

Comprehensive reparative effects of bacteriostatic poly(L-lactide-co-glycolide)/poly(L-lactide-co-ε-caprolactone) electrospinning membrane on alveolar bone defects in progressive periodontitis.

作者信息

Liu Yiming, Zhao Yun, Zhu Wanchun, Han Mei, Mi Fanglin, Wang Bing

机构信息

Department of Stomatology, North Sichuan Medical College & Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Department of Chemistry, School of Pharmacy, North Sichuan Medical College, Nanchong, China.

出版信息

J Biomed Mater Res B Appl Biomater. 2023 Mar;111(3):513-525. doi: 10.1002/jbm.b.35168. Epub 2022 Oct 5.

Abstract

Periodontitis is a chronic inflammatory disease that leads to the loss of alveolar bone, among several studies focusing on reconstructing periodontal bone caused by periodontitis, guided bone regeneration (GBR) is a promising approach. In this study a serial clinically applied antibiotics loaded poly(L-lactide-co-glycolide)/poly(L-lactide-co-ε-caprolactone) (PLGA/PLCA) fibrous mesh to prevent and reconstruct defective bone in periodontitis were prepared by electrospinning. Incorporation of antibiotics promoted the hydrophilicity but decreased the crystallinity of PLGA/PLCA membranes. Antibiotics could be sustained released from membranes. Metronidazole, minocycline, and doxycycline incorporated membranes could suppress Porphyromonas gingivalis (P. gingivalis) within 21 days in vitro. Metronidazole and minocycline incorporated membranes decreased 41% and 55.5% colony counts in rat gingival crevicular fluid in vivo. Minocycline-loaded membrane could support the proliferation of MC3T3-E1 cells and maintained 79% viability of human ligament fibroblasts cultured on it. And MC3T3-E1 cells could undergo osteoblastic differentiation when cultured with pure PLGA/PLCA membrane and minocycline incorporated membrane. Then in vivo repairable effects of those antibiotics loaded membranes were evaluated in alveolar bone defected P. gingivalis infected model. The application of minocycline loaded membranes, effectively prevented the bone resorption of periodontitis caused by P. gingivalis. After been treated with minocycline incorporated membrane, volume of defected bone of maintained at about 50% level of control rats. 8 weeks post-operation, newly regenerated bone was observed in the operative alveolar bone of the pure PLGA/PLCA membrane, metronidazole and minocycline incorporated PLGA/PLCA membrane treated groups. Minocycline/PLGA/PLCA electrospinning membrane is a promising GBR material that can be applied to guide regeneration of periodontitis-induced alveolar bone damage.

摘要

牙周炎是一种导致牙槽骨丧失的慢性炎症性疾病。在多项致力于重建由牙周炎引起的牙周骨的研究中,引导骨再生(GBR)是一种很有前景的方法。在本研究中,通过静电纺丝制备了一系列临床应用的载抗生素聚(L-丙交酯-共-乙交酯)/聚(L-丙交酯-共-ε-己内酯)(PLGA/PLCA)纤维网,以预防和重建牙周炎中的骨缺损。抗生素的加入提高了PLGA/PLCA膜的亲水性,但降低了其结晶度。抗生素可从膜中持续释放。载有甲硝唑、米诺环素和多西环素的膜在体外21天内可抑制牙龈卟啉单胞菌(P. gingivalis)。载有甲硝唑和米诺环素的膜使大鼠体内龈沟液中的菌落数分别减少了41%和55.5%。载有米诺环素的膜可支持MC3T3-E1细胞的增殖,并使培养在其上的人韧带成纤维细胞保持79%的活力。当与纯PLGA/PLCA膜和载有米诺环素的膜一起培养时,MC3T3-E1细胞可发生成骨分化。然后在牙龈卟啉单胞菌感染的牙槽骨缺损模型中评估了这些载抗生素膜的体内修复效果。载有米诺环素的膜的应用有效地预防了由牙龈卟啉单胞菌引起的牙周炎的骨吸收。用载有米诺环素的膜治疗后,缺损骨的体积维持在对照大鼠约50%的水平。术后8周,在纯PLGA/PLCA膜、载有甲硝唑和米诺环素的PLGA/PLCA膜治疗组的手术牙槽骨中观察到新再生的骨。米诺环素/PLGA/PLCA静电纺丝膜是一种很有前景的GBR材料,可用于引导牙周炎诱导的牙槽骨损伤的再生。

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