Baikov Institute of Metallurgy and Materials Science of the Russian Academy of Sciences, Moscow, Russia.
Institute of Strength Physics and Materials Science of the Siberian Branch of Russian Academy of Sciences, Tomsk, Russia.
J Biomater Sci Polym Ed. 2020 Aug;31(11):1405-1420. doi: 10.1080/09205063.2020.1760699. Epub 2020 May 5.
The novelty of the work lies in the creation and study of the physical and biological properties of biodegradable polymer coatings for stents based on poly(lactic-co-glycolic acid) (PLGA). Polymer coatings are capable of prolonged and directed release of molecules with a high molecular weight, in particular, protein molecules of prourokinase (m.w. 54 kDa). A technology has been developed to create coatings having a relative elongation of 40% to 165% and a tensile strength of 25-65 MPa. Coatings are biodegradable; the rate of degradation of the polymer in an isotonic solution varies in the range of 0.05%-1.0% per day. The created coatings are capable of controlled release of the protein of prourokinase, while about 90% of the molecules of prourokinase retain their enzymatic activity. The rate of release of prourokinase can vary from 0.01 to 0.08 mg/day/cm. Coatings do not have a short-term toxic effect on mammalian cells. The mitotic index of cells growing on coatings is approximately 1.5%. When implanting the developed polymers in animals in the postoperative period, there are no complications. Histological examination did not reveal pathological processes. When implanting individual polymers 60 days after surgery, only traces of PLGA are detected. Thus, a biodegradable composite mechanically resistant polymer capable of prolonged release of the high molecular weight prourokinase enzyme has been developed.
这项工作的新颖之处在于基于聚(丙交酯-乙交酯)(PLGA)的可生物降解聚合物支架涂层的物理和生物特性的创造和研究。聚合物涂层能够长时间和定向释放具有高分子量的分子,特别是尿激酶原(m.w. 54 kDa)的蛋白质分子。已经开发出一种技术来制造具有 40%至 165%相对伸长率和 25-65 MPa 拉伸强度的涂层。涂层是可生物降解的;在等渗溶液中聚合物的降解速度在每天 0.05%-1.0%的范围内变化。所制备的涂层能够控制尿激酶原蛋白的释放,同时约 90%的尿激酶原分子保留其酶活性。尿激酶原的释放速度可以从 0.01 到 0.08 mg/天/cm 变化。涂层对哺乳动物细胞没有短期的毒性作用。在涂层上生长的细胞的有丝分裂指数约为 1.5%。在动物中植入开发的聚合物后,没有并发症。组织学检查没有发现病理过程。在手术后 60 天植入单个聚合物时,仅检测到 PLGA 的痕迹。因此,已经开发出一种可生物降解的复合机械强度聚合物,能够长时间释放高分子量的尿激酶原酶。