缓释抗菌微球复合型组织工程材料水凝胶的制备及性能评价.

Preparation and performance evaluation of composite tissue-engineered material hydrogel with sustained-release antibacterial microspheres.

BACKGROUND: Oxidized hydroxypropyl methylcellulose-sodium hyaluronate hydrogel system exerts perfect mechanical properties, biocompatibility, and degradability, can be employed as a tissue engineered scaffold to protect and support injured tissues, and can also be applied as a drug carrier to achieve a regional sustained-release effect. OBJECTIVE: To prepare sustained-release antibacterial microsphere composite tissue-engineered material hydrogel, and investigate its physical and chemical, biological, osteoinductive, and antibacterial properties. METHODS: Using poly(lactic-co-glycolicacid), chitosan, and sodium hyaluronate as materials, a porous microsphere carrier with a multilayer structure was prepared by the emulsion method. Vancomycin hydrochloride was loaded to prepare sustained-release antibacterial microspheres. Oxidized hydroxypropyl methylcellulose-hydrazide-modified sodium hyaluronate was utilized as the matrix to prepare an injectable hydrogel. Different mass concentrations of antibacterial sustained-release microspheres (0.1, 0.2, and 0.3 g/mL) were added to the hydrogel to prepare an injectable hydrogel containing sustainedrelease antibacterial microspheres. The physical and chemical properties (determination of gel-forming time, swelling performance, degradation performance), biological properties (cytotoxicity, cell hemolysis), and osteogenic properties (alkaline phosphatase activity and osteogenic genes RUN-x2, bone morphogenetic protein 2, osteocalcin, type I collagen expression levels), and antibacterial properties were tested and evaluated. RESULTS AND CONCLUSION: (1) The three kinds of sustained-release antibacterial microsphere hydrogels had good gel-forming properties and a small swelling ratio. The in vitro degradation scanning electron microscope results exhibited that the hydrogels had stable self-degradation properties. (2) The cytotoxicity experiment displayed that when the added number of sustained-release antibacterial microspheres was less than or equal to 0.2 g/mL, the hydrogel did not have remarkable cytotoxicity (the relative growth rate of cells within 7 days was all greater than 80%). The hemolysis experiment demonstrated that cell hemolysis rate of three kinds of the sustained-release antibacterial microsphere hydrogel was less than 2%, without obvious cell hemolysis. (3) Three kinds of sustained-release antibacterial microsphere hydrogels could increase the osteogenic gene RUN-x2, bone morphogenetic protein 2, type I collagen, osteocalcin contents, and alkaline phosphatase production in MG-63 cells. (4) These hydrogels could suppress the growth of Staphylococcus aureus continuously and for a long time, and the antibacterial ability of the hydrogels increased with the increased amount of sustained-release antibacterial microspheres. (5) These results show that the prepared injectable antibacterial microsphere hydrogel has perfect sustained-release antibacterial, osteogenic, and osteoinductive capabilities, as well as good biohistocompatibility and degradability. [ABSTRACT FROM AUTHOR]

背景：氧化羟丙基甲基纤维素-透明质酸钠水凝胶体系具有良好的力学性能、生物相容性与降解性, 可作为组织工程支架对受损组织起保 护支撑作用, 也可作为药物载体实现局部缓释作用. 目的：制备缓释抗菌微球复合型组织工程材料水凝胶, 研究其理化性能、生物学性能、骨诱导性能和抗菌性能. 方法：以聚乳酸乙醇酸共聚物、壳聚糖和透明质酸钠为材料, 通过乳液法制备出具有多层结构的多孔微球载体, 并对酸万古霉素进行负 载, 制备出抗菌缓释微球; 以氧化羟丙基羧甲基纤维素和胺化透明质酸钠为基质制备成可注射水凝胶, 并将不同质量浓度的抗菌缓释微球 (0.1, 0.2, 0.3 g/mL)添加到水凝胶中, 制备出载抗菌缓释微球的可注射水凝胶, 对其理化性能(成胶时间测定、溶胀性能、降解性能)、生 物学性能(细胞毒性、细胞溶血性)及成骨性能(碱性磷酸酶活性及诱导成骨基因RUN-x2、骨形态发生蛋白2、骨钙蛋白、Ⅰ型胶原蛋白表达 水平)、抗菌性能进行检测及评价. 结果与结论：①3种载抗菌缓释微球水凝胶具有良好的成胶性能与较小的溶胀比; 体外降解扫描电镜结果显示, 水凝胶具有稳定的自身降 解性能; ②细胞毒性实验显示, 当抗菌缓释微球添加量≤0.2 g/mL时, 水凝胶无明显的细胞毒性(7 d内细胞的相对增殖率均大于80%); 溶 血实验显示, 3种载抗菌缓释微球水凝胶的细胞溶血率小于2%, 无明显细胞溶血; ③3种载抗菌缓释微球水凝胶均可提高MG-63细胞中成 骨基因RUN-x2、骨形态发生蛋白2、Ⅰ型胶原、骨钙蛋白含量及碱性磷酸酶的生成; ④3种水凝胶均可持续、长期地抑制金黄色葡萄球菌 的生长, 并且随着抗菌缓释微球添加量的增加水凝胶的抗菌能力增强; ⑤结果表明, 制备的可注射载抗菌微球水凝胶具有良好的缓释抗菌 及成骨、骨诱导能力, 同时具备较好的生物组织相容性、可降解性. [ABSTRACT FROM AUTHOR]

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