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用于引导组织再生/引导骨组织再生应用的载硝唑尼特聚(ε-己内酯)膜的研制与表征

Development and characterization of nitazoxanide-loaded poly(ε-caprolactone) membrane for GTR/GBR applications.

作者信息

Arora Varuni, Lin Ruby Yu-Tong, Tang Yi Ling, Tan Kai Soo, Rosa Vinicius, Sriram Gopu, Dubey Nileshkumar

机构信息

Faculty of Dentistry, National University of Singapore, Singapore 119085, Singapore.

Faculty of Dentistry, National University of Singapore, Singapore 119085, Singapore; ORCHIDS: Oral Care Health Innovations and Designs Singapore, National University of Singapore, Singapore 119085, Singapore.

出版信息

Dent Mater. 2024 Dec;40(12):2164-2172. doi: 10.1016/j.dental.2024.10.007. Epub 2024 Oct 22.

Abstract

OBJECTIVE

Guided tissue/guided bone regeneration (GTR/GBR) membranes are widely used for periodontal bone regeneration, but their success depends on a bacteria-free environment. Systemic antibiotic treatment often proves inadequate, moreover, the increasing prevalence of antibiotic resistance in oral infections exacerbates this challenge. This study aimed to fabricate antibacterial membranes using a new class of antibiotics for local drug delivery, to eradicate infections and promote tissue regeneration.

METHODS

Membranes loaded with nitazoxanide (NTZ) were fabricated via electrospinning using poly(ε-caprolactone) (PCL) with varying concentrations of NTZ (0 %, 2.5 %, and 5 % w/w) relative to the polymer weight. Morphochemical of NTZ-loaded membranes were assessed using scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and Fourier Transform Infrared spectroscopy (FTIR). Mechanical properties were evaluated using universal testing machine and NTZ release profile from membranes was determined by spectrophotometer (λ = 444) for 14 days. Antimicrobial efficacy against periodontal pathogens, cell compatibility and mineralization were evaluated using periodontal ligament stem cells (PDLSCs).

RESULTS

Optimized spinning parameter maintained a uniform fiber diameter and successful loading of NTZ was confirmed by SEM-EDS and FTIR. NTZ incorporation did not significantly affect mechanical properties, whereas the drug release kinetics showed an initial burst, followed by sustained release over 14 days. NTZ-loaded membranes demonstrated antibacterial activity against Aggregatibacter actinomycetemcomitans (Aa) and Fusobacterium nucleatum (Fn). Importantly, the presence of NTZ showed minimal cell toxicity; however, it reduced the mineralization potential compared with that of the pure PCL membrane, which increased over time.

SIGNIFICANCE

Taken together, these findings established that NTZ-loaded membranes could be promising barrier membrane to counteract microbial environment and aid periodontal bone regeneration.

摘要

目的

引导组织/引导骨再生(GTR/GBR)膜广泛用于牙周骨再生,但其成功取决于无菌环境。全身抗生素治疗往往证明是不足的,此外,口腔感染中抗生素耐药性的日益普遍加剧了这一挑战。本研究旨在使用一类新型抗生素制备抗菌膜,用于局部药物递送,以消除感染并促进组织再生。

方法

通过静电纺丝制备负载硝唑尼特(NTZ)的膜,使用聚(ε-己内酯)(PCL),相对于聚合物重量,NTZ的浓度不同(0%、2.5%和5% w/w)。使用扫描电子显微镜-能量色散光谱(SEM-EDS)和傅里叶变换红外光谱(FTIR)评估负载NTZ的膜的形态化学。使用万能试验机评估力学性能,并通过分光光度计(λ = 444)测定膜中NTZ的释放曲线,持续14天。使用牙周膜干细胞(PDLSCs)评估对牙周病原体的抗菌效果、细胞相容性和矿化作用。

结果

优化的纺丝参数保持了均匀的纤维直径,SEM-EDS和FTIR证实成功负载了NTZ。NTZ的掺入对力学性能没有显著影响,而药物释放动力学显示出初始的突释,随后在14天内持续释放。负载NTZ的膜对伴放线聚集杆菌(Aa)和具核梭杆菌(Fn)表现出抗菌活性。重要的是,NTZ的存在显示出最小的细胞毒性;然而,与纯PCL膜相比,它降低了矿化潜力,而纯PCL膜的矿化潜力随时间增加。

意义

综上所述,这些发现表明负载NTZ的膜可能是一种有前途的屏障膜,可对抗微生物环境并有助于牙周骨再生。

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