Stepanova Mariia, Averianov Ilia, Gofman Iosif, Shevchenko Natalia, Rubinstein Artem, Egorova Tatiana, Trulioff Andrey, Nashchekina Yulia, Kudryavtsev Igor, Demyanova Elena, Korzhikova-Vlakh Evgenia, Korzhikov-Vlakh Viktor
Institute of Macromolecular Compounds, Russian Academy of Sciences, 199004 St. Petersburg, Russia.
Institute of Experimental Medicine, 197376 St. Petersburg, Russia.
Polymers (Basel). 2023 Sep 30;15(19):3957. doi: 10.3390/polym15193957.
Annual bone grafting surgeries due to bone fractures, resections of affected bones, skeletal anomalies, osteoporosis, etc. exceed two million worldwide. In this regard, the creation of new materials for bone tissue repair is one of the urgent tasks of modern medicine. Additive manufacturing, or 3D printing, offers great opportunities for the development of materials with diverse properties and designs. In this study, the one-pot technique for the production of 3D scaffolds based on poly(ε-caprolactone) (PCL) loaded with an antibiotic or anti-inflammatory drug was proposed. In contrast to previously described methods to prepare drug-containing scaffolds, drug-loaded PCL scaffolds were prepared by direct 3D printing from a polymer/drug blend. An investigation of the mechanical properties of 3D-printed scaffolds containing 0.5-5 wt% ciprofloxacin (CIP) or dexamethasone (DEX) showed almost no effect of the drug (compression modulus ~70-90 MPa) compared to unfilled PCL (74 MPa). At the same time, introducing the drug and increasing its content in the PCL matrix contributed to a 1.8-6.8-fold decrease in the specific surface area of the scaffold, depending on composition. The release of CIP and DEX in phosphate buffer solution and in the same buffer containing lipase revealed a faster release in enzyme-containing medium within 45 days. Furthermore, drug release was more intensive from scaffolds with a low drug load. Analysis of the release profiles using a number of mathematical dissolution models led to the conclusion that diffusion dominates over other probable factors. In vitro biological evaluation of the scaffolds containing DEX showed moderate toxicity against osteoblast-like and leukemia monocytic cells. Being 3D-printed together with PCL both drugs retain their biological activity. PCL/CIP and PCL/DEX scaffolds demonstrated antibacterial properties against (a total inhibition after 48 h) and anti-inflammatory activity in experiments on TNFα-activated monocyte cells (a 4-time reduction in CD-54 expression relative to control), respectively.
全球范围内，因骨折、患骨切除、骨骼异常、骨质疏松等原因每年进行的骨移植手术超过两百万例。在这方面，研发用于骨组织修复的新材料是现代医学的紧迫任务之一。增材制造，即3D打印，为开发具有多样性能和设计的材料提供了巨大机遇。在本研究中，提出了一种基于负载抗生素或抗炎药物的聚（ε-己内酯）（PCL）制备3D支架的一锅法技术。与先前描述的制备含药支架的方法不同，载药PCL支架是通过从聚合物/药物共混物直接进行3D打印制备的。对含有0.5 - 5 wt%环丙沙星（CIP）或地塞米松（DEX）的3D打印支架的力学性能研究表明，与未填充的PCL（74 MPa）相比，药物对其几乎没有影响（压缩模量约为70 - 90 MPa）。同时，根据组成不同，在PCL基质中引入药物并增加其含量会使支架的比表面积降低1.8 - 6.8倍。CIP和DEX在磷酸盐缓冲溶液以及含有脂肪酶的相同缓冲溶液中的释放表明，在含酶介质中45天内释放更快。此外，低载药量支架的药物释放更强烈。使用多种数学溶解模型对释放曲线进行分析得出结论，扩散在其他可能因素中占主导地位。对含DEX支架的体外生物学评估显示，其对成骨样细胞和白血病单核细胞具有中等毒性。两种药物与PCL一起进行3D打印时均保留其生物活性。PCL/CIP和PCL/DEX支架分别对[具体细菌]表现出抗菌性能（48小时后完全抑制），并且在TNFα激活的单核细胞实验中具有抗炎活性（相对于对照，CD - 54表达降低4倍）。
