Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
Acta Biomater. 2019 Jan 1;83:245-256. doi: 10.1016/j.actbio.2018.10.039. Epub 2018 Oct 27.
Antimicrobial peptides (AMPs) are currently receiving interest as an alternative to conventional antibiotics to treat biomaterial-associated infection. However, the inherent instability of such peptides often limits their efficacy in intended clinical applications. Covalent immobilization of AMPs to surfaces is one strategy to increase the long-term stability and minimize the toxicity. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was used to modify elastin-like polypeptide (ELP) surface coatings containing cell-adhesive peptide domains (RGD) using covalent chemistry. The AMP retained its antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa when covalently bonded to ELP surfaces. Simultaneously, the AMP functionalization had insignificant effect on the viability, function, and differentiation of human osteosarcoma MG63 cells and human mesenchymal stem cells (hMSCs). Furthermore, stability of the immobilized AMP in human blood serum was investigated, and the results suggested that the AMP preserved its antibacterial activity up to 24 h. Combined, the results show that covalently attached AMPs onto RGD-containing ELP are an excellent candidate as an antimicrobial coating for medical devices. STATEMENT OF SIGNIFICANCE: Biomaterial associated infection, caused by adherent biofilm, is usually difficult to treat. There is a high demand for new materials and treatments to decrease the infection rates, especially with increasing threats concerning resistant bacteria. Formation of biofilms on medical devices lowers the bacteria susceptibility towards traditional antibiotics and also circumvent our immune system often resulting in revisional surgery and extensive use of antibiotics. One promising strategy is to develop surfaces having low bacterial attractiveness or bacterial killing properties, but still retaining the main function of the device. In this study, we have developed an implant coating that demonstrates a high antimicrobial effect and at the same time showing no negative affect on human cells.
抗菌肽 (AMPs) 作为治疗生物材料相关感染的传统抗生素替代品,目前正受到关注。然而,这些肽类物质的固有不稳定性往往限制了它们在预期临床应用中的疗效。通过将 AMP 共价固定在表面上是提高长期稳定性和最小化毒性的一种策略。在这项工作中,使用抗菌肽 RRPRPRPRPWWWW-NH2(RRP9W4N)通过共价化学修饰含有细胞黏附肽结构域(RGD)的弹性蛋白样多肽(ELP)表面涂层。当 AMP 共价键合到 ELP 表面时,它保留了对表皮葡萄球菌、金黄色葡萄球菌和铜绿假单胞菌的抗菌活性。同时,AMP 功能化对人骨肉瘤 MG63 细胞和人间充质干细胞(hMSC)的活力、功能和分化没有显著影响。此外,还研究了固定化 AMP 在人血清中的稳定性,结果表明 AMP 保持其抗菌活性长达 24 小时。综上所述,结果表明,将 AMP 共价连接到含 RGD 的 ELP 上是作为医疗器械抗菌涂层的优秀候选物。
生物材料相关感染是由附着的生物膜引起的,通常难以治疗。降低感染率的新材料和治疗方法需求很高,尤其是随着耐药菌威胁的增加。医疗器械上生物膜的形成降低了细菌对传统抗生素的敏感性,也常常规避了我们的免疫系统,导致经常需要进行翻修手术和广泛使用抗生素。一种有前途的策略是开发具有低细菌吸引力或杀菌特性的表面,但同时仍保留设备的主要功能。在这项研究中,我们开发了一种具有高抗菌效果的植入物涂层,同时对人体细胞没有负面影响。