搭载米诺环素-壳聚糖纳米粒复合水凝胶用于牙周炎治疗的初步研究  

Application of gelatin methacryloyl/minocycline-chitosan-nanoparticles composite hydrogel for the treatment of periodontitis

作　　者：由子樱 伍彦霖 孙一民 王振铭 叶玲 You Ziying;Wu Yanlin;Sun Yimin;Wang Zhenming;Ye Ling(State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China)

机构地区：[1]口腔疾病研究国家重点实验室、国家口腔疾病临床医学研究中心、四川大学华西口腔医院,成都610041

出　　处：《华西口腔医学杂志》2023年第1期11-20,共10页West China Journal of Stomatology

基　　金：国家杰出青年科学基金(81825005)。

摘　　要：目的 通过体内外实验探究搭载米诺环素-壳聚糖纳米粒(MCN)的甲基丙烯酸化明胶(GelMA)水凝胶在牙周炎治疗中的效果。方法 采用离子凝胶法合成MCN,并将MCN包裹在GelMA水凝胶中得到GelMA/MCN复合水凝胶。通过透射电镜、扫描电镜、傅里叶红外光谱对材料进行表征分析,考察材料的降解速率、米诺环素释放速率。检测GelMA/MCN水凝胶对于牙龈卟啉单胞菌(P. gingivalis)的抗菌能力,并筛选出有效抗菌浓度。评估GelMA/MCN水凝胶的生物相容性和成骨能力。构建大鼠牙周炎模型,评价GelMA/MCN水凝胶在牙周炎治疗中的效果。结果 表征测试结果显示,成功构建了粒径在80 nm左右的MCN;MCN的修饰对GelMA水凝胶形貌无明显影响。MCN和GelMA/MCN均可以缓慢、稳定地释放米诺环素。当GelAM/MCN水凝胶的MCN含量大于等于0.2 mg·mL^(-1)时,P. gingivalis生长完全被抑制。在体外模拟牙周炎的酶促降解环境下,GelMA/MCN水凝胶在有效抗菌浓度下具有良好的生物相容性;体内实验证实该水凝胶可有效阻止牙周炎骨缺损的进一步发展,促进骨缺损修复。结论 GelMA/MCN复合水凝胶能稳定、缓慢地释放米诺环素,在有效抗菌浓度下保护细胞活力,并促进牙周炎骨缺损的修复。Objective This study aimed to investigate the feasibility of gelatin methacryloyl(GelMA) hydrogel loaded with minocycline-chitosan-nanoparticles(MCN) for the treatment of periodontitis in vitro and vivo. Methods MCN were synthesized by ionic gel method. GelMA/MCN composite hydrogels were prepared by compounding MCN with GelMA hydrogel. The materials were characterized by transmission electron microscope, scanning electron microscopy, and Fourier transform infrared spectroscopy. The degradation behavior and drug release rates of hydrogels were evaluated. The antibacterial activity of GelMA/MCN hydrogel against Porphyromonas gingivalis was detected, and the minimum antibacterial concentration was determined. Biocompatibility and osteogenic experiments were conducted under a simulated periodontitis environment. A rat model of periodontitis was constructed to observe the therapeutic effects of GelMA/MCN hydrogel. Results MCN was successfully synthesized with a particle size of about 80 nm, while the structures of GelMA/MCN had no significant differences from GelMA. MCN and GelMA/MCN released minocycline slowly and steadily. Bacterial growth was completely inhibited when the MCN concentration was higher than or equal to 0.2 mg·mL^(-1). GelMA/MCN hydrogels exhibited good biocompatibility at effective antimicrobial concentrations under the simulated periodontitis environment with the enzyme. The in vivo results showed that GelMA/MCN prevented the progression of periodontitis and promoted the repair of bone defects. Conclusion GelMA/MCN composite hydrogel can release minocycline slowly and steadily and has good antibacterial activity and biocompatibility to promote the repair of periodontitis bone defects.

关 键 词：米诺环素 壳聚糖 水凝胶 药物缓释 牙周炎 

分 类 号：R318.08[医药卫生—生物医学工程]