Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China.
Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China.
Biomaterials. 2023 Feb;293:121957. doi: 10.1016/j.biomaterials.2022.121957. Epub 2022 Dec 12.
Aging population has been boosting the need for orthopedic implants. However, biofilm has been a major obstacle for orthopedic implants due to its insensitivity to antibiotics and tendency to drive antimicrobial resistance. Herein, an antibacterial polypeptide coating with excellent in vivo adhesive capacity was prepared to prevent implants from forming biofilms and inducing acquired antibiotic resistance. A peptide-based copolymer, poly[phenylalanine-stat-lysine]-block-3,4-dihydroxy-l-phenylalanine [Poly(Phe-stat-Lys)-DOPA] was modularly designed, where poly(Phe-stat-Lys) is antibacterial polypeptide with high antibacterial activity, and DOPA provides strong adhesion in both wet and dry microenvironments. Meanwhile, compared to traditional "graft-onto" methods, this antibacterial coating can be facilely achieved by immersing Titanium substrates into antibacterial polypeptide solution for 5 min at room temperature. The poly(Phe-stat-Lys)-DOPA polymer showed good antibacterial activity with minimum inhibitory concentrations against S. aureus and E. coli of 32 and 400 μg/mL, respectively. Compared to obvious antimicrobial resistance of S. aureus after continuous treatment with vancomycin, this antibacterial coating doesn't drive antimicrobial resistance upon long-term utilization. Transcriptome sequencing and qPCR tests further confirmed that the antibacterial coating was able to inhibit the expression of multiple peptide resistance factor (mprF) and lipoteichoic acid modification D-alanylation genes (dltB and dltC) that can increase the net positive charge of bacterial cell wall to induce the resistance to cationic antimicrobial peptides. In vivo experiments confirmed that this poly(Phe-stat-Lys)-DOPA coating can both effectively prevent biofilm formation through surface contact sterilization and avoid local and systemic infections. Overall, we proposed a facile method for preparing antibacterial orthopedic implants with longer indwelling time and without inducing antimicrobial resistance by coating a polypeptide-based polymer on the implants.
人口老龄化一直在增加对骨科植入物的需求。然而，由于生物膜对抗生素不敏感且容易导致抗菌药物耐药性，它一直是骨科植入物的主要障碍。在此，我们制备了一种具有优异体内黏附能力的抗菌多肽涂层，以防止植入物形成生物膜并诱导获得性抗生素耐药性。设计了一种基于肽的共聚物，聚[苯丙氨酸-赖氨酸]-嵌段-3,4-二羟基-L-苯丙氨酸[聚（Phe-stat-Lys）-DOPA]，其中聚（Phe-stat-Lys）是具有高抗菌活性的抗菌多肽，DOPA 在湿、干微环境中均提供强黏附力。同时，与传统的“接枝到”方法相比，这种抗菌涂层可以通过将钛基底在室温下浸入抗菌多肽溶液中 5 分钟来简单地实现。聚（Phe-stat-Lys）-DOPA 聚合物表现出良好的抗菌活性，对金黄色葡萄球菌和大肠杆菌的最小抑菌浓度分别为 32 和 400μg/mL。与万古霉素连续处理后金黄色葡萄球菌明显产生抗菌药物耐药性相比，这种抗菌涂层在长期使用过程中不会产生抗菌药物耐药性。转录组测序和 qPCR 测试进一步证实，抗菌涂层能够抑制多种肽耐药因子（mprF）和脂磷壁酸修饰 D-丙氨酸化基因（dltB 和 dltC）的表达，这些基因可以增加细菌细胞壁的净正电荷，从而诱导对阳离子抗菌肽的耐药性。体内实验证实，这种聚（Phe-stat-Lys）-DOPA 涂层可以通过表面接触杀菌有效防止生物膜形成，并避免局部和全身感染。总之，我们提出了一种简便的方法，通过在植入物表面涂覆基于多肽的聚合物来制备具有更长留置时间且不会诱导抗菌药物耐药性的抗菌骨科植入物。
