可吸收抗菌胆道支架的制备及其生物相容性研究
PDF下载 (368)傅俊辉,黄 静,徐 锐,戴晨怡,刘烨磊,李张辉,骆 阳,竺亚斌,陆才德.可吸收抗菌胆道支架的制备及其生物相容性研究[J].宁波大学学报(理工版),2022,35(6):54-62.DOI:
FU Junhui,HUANG Jing,XU Rui,DAI Chenyi,LIU Yelei,LI Zhanghui,LUO Yang,ZHU Yabin,LU Caide.Preparation and biocompatibility of absorbable antibacterial biliary stent[J].Journal of Ningbo University(Natural Science & Engineering Edition),2022,35(6):54-62.DOI:
| Title: | Preparation and biocompatibility of absorbable antibacterial biliary stent |
| 作者: | 傅俊辉, 黄 静, 徐 锐, 戴晨怡, 刘烨磊, 李张辉, 骆 阳, 竺亚斌, 陆才德 |
| Author(s): | FU Junhui, HUANG Jing, XU Rui, DAI Chenyi, LIU Yelei, LI Zhanghui, LUO Yang, ZHU Yabin, LU Caide |
| 关键词: | 胆道支架; 力学性能; 抗菌活性; 生物降解性; 生物相容性 |
| Keywords: | biliary stent; mechanical properties; antibacterial activity; biodegradability; biocompatibility |
| 分类号: | R333 |
| 文献标识码: | A |
| 摘要: | 胆道梗阻是临床上高发病率和高死亡率的疾病之一, 而植入可吸收支架以替代或扩张梗阻病灶是理想的治疗方法之一. 以聚(L-丙交酯-co-ε-己内酯)(Poly (L-lactide-co-ε-caprolactone), PLCL) (丙交酯与己内酯的质量比为8020)和聚L-丙交酯(Poly (L-lactide), PLLA)为基质制备了管状支架, 然后以聚六亚甲基胍盐酸盐(Polyhexamethylene Guanidine Hydrochloride, PHMG)涂覆于支架表面制备抗菌涂层, 研究该支架的理化性质、抗菌活性以及在动物体内的生物相容性和十二指肠的通畅性. 结果表明 PLCLPLLA=5050(P50-50)材料的力学性能在所有配比材料中最好. 经PHMG包覆后的PP50-50皮下植入时, 具有良好的抗菌活性和体内良好的生物相容性. 用PP50-50膜制成的支架在28d内在小鼠十二指肠内具有良好的通畅性和支撑性. 组织学和免疫荧光染色显示, 炎症反应发生在早期, 随后消退. 这些结果表明, PP50-50支架可能是治疗胆道狭窄的一种良好选择. |
| Abstract: | Biliary obstruction is a disease with high morbidity and mortality. Stent implantation is a promising method to treat the obstruction. In the present study, poly(L-lactide-co-ε-caprolactone)(PLCL, LACL, feed ratio is 8020) and poly (L-lactide)(PLLA) were used as matrices to fabricate biliary stents. PLCL were blended with PLLA in various ratios to prepare biodegradable polymeric film, with polyhexamethylene guanidine hydrochloride (PHMG) being used as the antibacterial surface layer. The physicochemical properties, antibacterial activity, and biocompatibility and patency in animals of the stent were investigated. The results show that the blend with PLCLPLLA=5050(P50-50) had the best mechanical properties and performance among all the tested materials. After coating with PHMG(PP50-50), PP50-50 had good antibacterial activity and in vivo excellent biocompatibility along with subcutaneous implantation. The stent made from PP50-50 film showed good patency and supportability in the duodenum of mice within 28 days. The histological and immunofluorescent staining showed that the inflammatory reaction occurred in the initial stage and subsequently subsided. These results suggest that the PP50-50 stent might be a good choice for biliary substitute without stricture occurrence. |
| 参考文献 /References: | [1] 郭振, 尉海涛, 刘全,等. 可降解支架与金属药物洗脱支架对冠状动脉狭窄病变PCI术后安全性的影响[J]. 中国老年学杂志, 2018, 38(4):780-782. [2] 张亮, 马锋. 医用可降解聚乳酸的化学修饰及其作为胆道支架的应用[J]. 合成化学, 2017, 25(10):832-835. [3] Huespe P E, Oggero S, de Santibanes M, et al. Percutaneous patency recovery and biodegradable stent placement in a totally occluded hepaticojejunostomy after paediatric living donor liver transplantation[J]. Cardiovascular and Interventional Radiology, 2019, 42(3): 466-470. [4] Shi J H, Lü Y, Yu L, et al. Interest of a new biodegradable stent coated with paclitaxel on anastomotic wound healing after biliary reconstruction[J]. European Journal of Gastroenterology & Hepatology, 2013, 25(12):1415- 1423. [5] Grolich T, Crha M, Novotn? L, et al. Self-expandable biodegradable biliary stents in porcine model[J]. Journal of Surgical Research, 2015, 193(2):606-612. [6] 何伟, 王翔, 高莹, 等. 新型纳米银/聚氨酯胆道支架表面抗菌涂层的体外抑菌试验[J]. 中国组织工程研究与临床康复, 2011, 15(3):453-456. [7] 郝杰, 夏建民, 王博, 等. 新型可降解镁合金胆道支架在胆总管探查术中预防狭窄的作用[J]. 西安交通大学学报(医学版), 2017, 38(5):763-767. [8] 赵冬梅, 蒋丹娜, 刘侠. 塑料与金属胆管支架的材料特征及其生物相容性[J]. 中国组织工程研究与临床康复, 2011, 15(8):1463-1466. [9] Lorenzo-Zú?iga V, Moreno-de-Vega V, Marín I, et al. Biodegradable stents in gastrointestinal endoscopy[J]. World Journal of Gastroenterology, 2014, 20(9):2212- 2217. [10] Siiki A, Jesenofsky R, L?hr M, et al. Biodegradable biliary stents have a different effect than covered metal stents on the expression of proteins associated with tissue healing in benign biliary strictures[J]. Scandinavian Journal of Gastroenterology, 2016, 51(7):880-885. [11] Tanimoto Y, Tashiro H, Mikuriya Y, et al. Radiopaque biodegradable stent for duct-to-duct biliary reconstruction in pigs[J]. Langenbeck’s Archives of Surgery, 2016, 401 (4):513-517. [12] 刘文静, 李超, 戚晓升, 等. 抗菌型胆道支架的研究进展[J]. 中国医疗器械杂志. 2021, 45(2):183-187; 204. [13] 杨富春. 纳米银涂层的胆道塑料支架研制及其抗菌效果和延长支架通畅期的实验研究[D]. 杭州: 浙江大学, 2016. [14] Girard E, Chagnon G, Moreau-Gaudry A, et al. Evaluation of a biodegradable PLA-PEG-PLA internal biliary stent for liver transplantation: in vitro degradation and mechanical properties[J]. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2021, 109(3):410-419. [15] Sung J J Y, Lyon D J, Suen R, et al. Intravenous ciprofloxacin as treatment for patients with acute suppurative cholangitis: A randomized, controlled clinica trial[J]. Journal of Antimicrobial Chemotherapy, 1995, 35(6):855-864. [16] 王志勇, 李丽, 徐立群, 等. 胆道良恶性疾病患者胆汁菌群分布及药物敏感性的分析[J]. 中华消化内镜杂志, 2007, 24(6):445-446. [17] 尹大龙, 陆朝阳, 刘连新, 等. 莫西沙星对急性重症胆管炎疗效的临床研究[J]. 中国实用外科杂志, 2009, 29 (1):96-98. [18] 刘涛, 梁仲惠, 杜平, 等. 胆石症患者胆汁菌群分布及药敏分析[J]. 现代消化及介入诊疗, 2009, 14(4):210- 213. [19] 姜双应. 四种抗菌产品抑菌作用的实验室观察[J]. 中国消毒学杂志2008, 25(3):255-257. [20] Yamamoto K, Yoshioka T, Furuichii K, et al. Experi- mental study of Poly-L-Lactic acid biodegradable stents in normal canine bile ducts[J]. Cardiovascular and Interventional Radiology, 2011, 34(3):601-608. [21] 张诚, 杨玉龙, 吴萍, 等. 经内镜胆道金属支架置入术后胆道感染的原因及处理[J]. 肝胆胰外科杂志, 2014, 26(5):365-367; 371. [22] Obermeier A, Würstle S, Tübel J, et al. Novel antimicrobial coatings based on polylactide for plastic biliary stents to prevent post-endoscopic retrograde cholangiography cholangitis[J]. Journal of Antimicrobial Chemotherapy, 2019, 74(7):1911-1920. [23] Feng P P, Qiu H F, Luo Y, et al. Development of poloxamer hydrogels containing antibacterial guanidine- based polymers for healing of full-thickness skin wound[J]. ACS Biomaterials Science & Engineering, 2021, 7(9):4557-4568. [24] Kwon C I, Son J S, Kim K S, et al. Mechanical properties and degradation process of biliary self-expandable biodegradable stents[J]. Digestive Endoscopy, 2021, 33(7):1158-1169. |
| 备注/Memo: | 收稿日期:2022-05-12.宁波大学学报(理工版)网址:http://journallg.nbu.edu.cn/ 基金项目:宁波市医疗卫生品牌学科(PPXK2018-03). 第一作者:傅俊辉(1995-),男,浙江宁波人,在读硕士研究生,主要研究方向:肝胆胰外科.E-mail:334613683@qq.com *通信作者:陆才德(1951-),男,浙江台州人,教授,主要研究方向:肝胆胰外科.E-mail:lucaide@nbu.edu.cn 宁波大学学报(理工版)网址:http://journallg.nbu.edu.cn/ |