Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, United States; Department of Restorative Dentistry, School of Dentistry, Federal University of Pelotas, Pelotas, RS, Brazil.
Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, United States; Metallurgical and Materials Engineering Program (COPPE), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Dent Mater. 2022 Sep;38(9):1507-1517. doi: 10.1016/j.dental.2022.07.002. Epub 2022 Jul 23.
OBJECTIVES: This work sought to formulate photocrosslinkable chlorhexidine (CHX)-laden methacrylated gelatin (CHX/GelMA) hydrogels with broad spectrum of action against endodontic pathogens as a clinically viable cell-friendly disinfection therapy prior to regenerative endodontics procedures. METHODS: CHX/GelMA hydrogel formulations were successfully synthesized using CHX concentrations between 0.12 % and 5 % w/v. Hydrogel microstructure was evaluated by scanning electron microscopy (SEM). Swelling and enzymatic degradation were assessed to determine microenvironmental effects. Compression test was performed to investigate the influence of CHX incorporation on the hydrogels' biomechanics. The antimicrobial and anti-biofilm potential of the formulated hydrogels were assessed using agar diffusion assays and a microcosms biofilm model, respectively. The cytocompatibility was evaluated by exposing stem cells from human exfoliated deciduous teeth (SHEDs) to hydrogel extracts (i.e., leachable byproducts obtained from overtime hydrogel incubation in phosphate buffer saline). The data were analyzed using One- and Two-way ANOVA and Tukey's test (α = 0.05). RESULTS: CHX/GelMA hydrogels were effectively prepared. NMR spectroscopy confirmed the incorporation of CHX into GelMA. The addition of CHX did not change the micromorphology (pore size) nor the swelling profile (p > 0.05). CHX incorporation reduced the degradation rate of the hydrogels (p < 0.001); whereas, it contributed to increased compressive modulus (p < 0.05). Regarding the antimicrobial properties, the incorporation of CHX showed a statistically significant decrease in the number of bacteria colonies at 0.12 % and 0.5 % concentration (p < 0.001) and completely inhibited the growth of biofilm at concentration levels 1 %, 2 %, and 5 %. Meanwhile, the addition of CHX, regardless of the concentration, did not lead to cell toxicity, as cell viability values were above 70 %. SIGNIFICANCE: The addition of CHX into GelMA showed significant antimicrobial action against the pathogens tested, even at low concentrations, with the potential to be used as a cell-friendly injectable drug delivery system for root canal disinfection prior to regenerative endodontics.
目的：本研究旨在制备一种具有广谱抗菌作用的光交联型氯己定（CHX）负载甲基丙烯酰化明胶（CHX/GelMA）水凝胶，作为再生性牙髓治疗前一种可行的临床细胞友好型消毒疗法。
方法：通过将 CHX 浓度分别设置在 0.12%和 5%w/v，成功合成了 CHX/GelMA 水凝胶配方。通过扫描电子显微镜（SEM）评估水凝胶的微观结构。通过评估溶胀和酶降解来确定微环境的影响。通过压缩试验来研究 CHX 掺入对水凝胶生物力学的影响。通过琼脂扩散试验和微生境生物膜模型分别评估了配方水凝胶的抗菌和抗生物膜潜力。通过将人乳牙牙髓干细胞（SHEDs）暴露于水凝胶提取物（即在磷酸盐缓冲盐水中长期孵育水凝胶获得的可浸出副产物）来评估细胞相容性。使用单因素和双因素方差分析以及 Tukey 检验（α=0.05）对数据进行分析。
结果：成功制备了 CHX/GelMA 水凝胶。NMR 光谱证实了 CHX 掺入 GelMA。加入 CHX 并未改变微形态（孔径）或溶胀曲线（p>0.05）。CHX 的掺入降低了水凝胶的降解率（p<0.001）；而增加了压缩模量（p<0.05）。关于抗菌性能，在 0.12%和 0.5%浓度下，CHX 的掺入导致细菌菌落数量呈统计学显著减少（p<0.001），并且在 1%、2%和 5%浓度水平下完全抑制了生物膜的生长。同时，无论 CHX 浓度如何，添加 CHX 均不会导致细胞毒性，因为细胞活力值均高于 70%。
意义：在 GelMA 中添加 CHX 对测试的病原体表现出显著的抗菌作用，即使在低浓度下，也有可能作为再生性牙髓治疗前的一种细胞友好型可注射药物输送系统，用于根管消毒。
ACS Appl Mater Interfaces. 2020-4-8
Zhonghua Shao Shang Yu Chuang Mian Xiu Fu Za Zhi. 2022-7-20
J Mech Behav Biomed Mater. 2021-4
J Biomed Mater Res B Appl Biomater. 2024-5
ACS Appl Bio Mater. 2021-9-20
Polymers (Basel). 2024-6-12
Regen Med. 2025-8
Polymers (Basel). 2025-5-26
J Funct Biomater. 2025-2-24
ACS Biomater Sci Eng. 2019-8-12
Biomacromolecules. 2020-9-14
Am J Obstet Gynecol. 2020-5-12
ACS Appl Mater Interfaces. 2020-4-8
Int J Dent Hyg. 2019-3-25
J Appl Res Intellect Disabil. 2019-5
Clin Oral Investig. 2018-12-7
Zotero 插件