Dhingra Shaifali, Gaur Vidit, Saini Varsha, Rana Kajal, Bhattacharya Jayanta, Loho Thomas, Ray Sudip, Bajaj Avinash, Saha Sampa
Department of Materials Science and Engineering, Indian Institute of Technology Delhi, India.
Centre for Biomedical Engineering, Indian Institute of Technology Delhi, India.
Biomater Sci. 2022 Jul 12;10(14):3856-3877. doi: 10.1039/d2bm00245k.
Biomedical device or implant-associated infections caused by pathogenic bacteria are a major clinical issue, and their prevention and/or treatment remains a challenging task. Infection-resistant antimicrobial coatings with impressive cytocompatibility offer a step towards addressing this problem. Herein, we report a new strategy for constructing highly antibacterial as well as cytocompatible mixed polymer brushes onto the surface of 3D printed scaffold made of biodegradable tartaric acid-based aliphatic polyester blends. The mixed brushes were nothing but a combination of poly(3-dimethyl-(methacryloyloxyethyl) ammonium propane sulfonate) (polyDMAPS) and poly((oligo ethylene glycol) methyl ether methacrylate) (polyPEGMA) with varying chain length () of the ethylene glycol unit ( = 1, 6, 11, and 21). Both homo and copolymeric brushes of polyDMAPS with polyPEGMA exhibited antibacterial efficacy against both Gram positive and Gram negative pathogens such as () and () because of the combined action of bacteriostatic effects originating from strongly hydrated layers present in zwitterionic (polyDMAPS) and hydrophilic (polyPEGMA) copolymer brushes. Interestingly, a mixed polymer brush comprising polyDMAPS and polyPEGMA (ethylene glycol chain unit of 21) at 50/50 ratio provided zero bacterial growth and almost 100% cytocompatibility (tested using L929 mouse fibroblast cells), making the brush-modified biodegradable substrate an excellent choice for an infection-resistant and cytocompatible surface. An attempt was made to understand their extraordinary performance with the help of contact angle, surface charge analysis and nanoindentation study, which revealed the formation of a hydrophilic, almost neutral, very soft surface (99.99% reduction in hardness and modulus) after modification with the mixed brushes. This may completely suppress bacterial adhesion. Animal studies demonstrated that these brush-modified scaffolds are biocompatible and can mitigate wound infections. Overall, this study shows that the fascinating combination of an infection-resistant and cytocompatible surface can be generated on biodegradable polymeric surfaces by modulating the surface hardness, flexibility and hydrophilicity by selecting appropriate functionality of the copolymeric brushes grafted onto them, making them ideal non-leaching, anti-infective, hemocompatible and cytocompatible coatings for biodegradable implants.
由致病细菌引起的生物医学设备或植入物相关感染是一个重大的临床问题，其预防和/或治疗仍然是一项具有挑战性的任务。具有出色细胞相容性的抗感染抗菌涂层为解决这一问题迈出了一步。在此，我们报告了一种新策略，用于在由可生物降解的基于酒石酸的脂肪族聚酯共混物制成的3D打印支架表面构建具有高度抗菌性和细胞相容性的混合聚合物刷。这些混合刷是聚（3-二甲基-（甲基丙烯酰氧基乙基）铵丙烷磺酸盐）（聚DMAPS）和聚（（低聚乙二醇）甲基醚甲基丙烯酸酯）（聚PEGMA）的组合，其中乙二醇单元的链长（）不同（ = 1、6、11和21）。聚DMAPS与聚PEGMA的均聚物和共聚物刷由于两性离子（聚DMAPS）和亲水性（聚PEGMA）共聚物刷中存在的强水合层产生的抑菌作用的联合作用，对革兰氏阳性和革兰氏阴性病原体如（）和（）均表现出抗菌功效。有趣的是，由聚DMAPS和聚PEGMA（乙二醇链单元为21）以50/50比例组成的混合聚合物刷实现了零细菌生长和几乎100%的细胞相容性（使用L929小鼠成纤维细胞进行测试），使得经刷改性的可生物降解基材成为抗感染和细胞相容性表面的极佳选择。我们试图借助接触角、表面电荷分析和纳米压痕研究来理解它们的非凡性能，这些研究表明用混合刷改性后形成了亲水性、几乎中性、非常柔软的表面（硬度和模量降低99.99%）。这可能完全抑制细菌粘附。动物研究表明，这些经刷改性的支架具有生物相容性，能够减轻伤口感染。总体而言，这项研究表明，通过选择接枝到可生物降解聚合物表面的共聚物刷的适当官能团来调节表面硬度、柔韧性和亲水性，可以在可生物降解聚合物表面产生抗感染和细胞相容性表面的迷人组合，使其成为可生物降解植入物理想的无浸出、抗感染、血液相容性和细胞相容性涂层。
