{"title":"Cationic homopolypeptides: A versatile tool to design multifunctional antimicrobial nanocoatings","authors":"","doi":"10.1016/j.mtbio.2024.101168","DOIUrl":null,"url":null,"abstract":"<div><p>Postoperative infections are the most common complications faced by surgeons after implant surgery. To address this issue, an emerging and promising approach is to develop antimicrobial coatings using antibiotic substitutes. We investigated the use of polycationic homopolypeptides in a layer-by-layer coating combined with hyaluronic acid (HA) to produce an effective antimicrobial shield. The three peptide-based polycations used to make the coatings, poly(<span>l</span>-arginine) (PAR), poly(<span>l</span>-lysine), and poly(<span>l</span>-ornithine), provided an efficient antibacterial barrier by a contact-killing mechanism against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Moreover, this activity was higher for homopolypeptides containing 30 amino-acid residues per polycation chain, emphasizing the impact of the polycation chain length and its mobility in the coatings to deploy its contact-killing antimicrobial properties. However, the PAR-containing coating emerged as the best candidate among the three selected polycations, as it promoted cell adhesion and epithelial monolayer formation. It also stimulated nitric oxide production in endothelial cells, thereby facilitating angiogenesis and subsequent tissue regeneration. More interestingly, bacteria did not develop a resistance to PAR and (PAR/HA) also inhibited the proliferation of eukaryotic pathogens, such as yeasts. Furthermore, <em>in vivo</em> investigations on a (PAR/HA)-coated hernia mesh implanted on a rabbit model confirmed that the coating had antibacterial properties without causing chronic inflammation. These impressive synergistic activities highlight the strong potential of PAR/HA coatings as a key tool in combating bacteria, including those resistant to conventional antibiotics and associated to medical devices.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002291/pdfft?md5=296707409863368ddb37e8dba84213cc&pid=1-s2.0-S2590006424002291-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Materials Today Bio","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590006424002291","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Postoperative infections are the most common complications faced by surgeons after implant surgery. To address this issue, an emerging and promising approach is to develop antimicrobial coatings using antibiotic substitutes. We investigated the use of polycationic homopolypeptides in a layer-by-layer coating combined with hyaluronic acid (HA) to produce an effective antimicrobial shield. The three peptide-based polycations used to make the coatings, poly(l-arginine) (PAR), poly(l-lysine), and poly(l-ornithine), provided an efficient antibacterial barrier by a contact-killing mechanism against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Moreover, this activity was higher for homopolypeptides containing 30 amino-acid residues per polycation chain, emphasizing the impact of the polycation chain length and its mobility in the coatings to deploy its contact-killing antimicrobial properties. However, the PAR-containing coating emerged as the best candidate among the three selected polycations, as it promoted cell adhesion and epithelial monolayer formation. It also stimulated nitric oxide production in endothelial cells, thereby facilitating angiogenesis and subsequent tissue regeneration. More interestingly, bacteria did not develop a resistance to PAR and (PAR/HA) also inhibited the proliferation of eukaryotic pathogens, such as yeasts. Furthermore, in vivo investigations on a (PAR/HA)-coated hernia mesh implanted on a rabbit model confirmed that the coating had antibacterial properties without causing chronic inflammation. These impressive synergistic activities highlight the strong potential of PAR/HA coatings as a key tool in combating bacteria, including those resistant to conventional antibiotics and associated to medical devices.
术后感染是外科医生在植入手术后面临的最常见并发症。为解决这一问题,一种新兴且前景广阔的方法是使用抗生素替代品开发抗菌涂层。我们研究了在逐层涂层中使用多阳离子均聚多肽与透明质酸(HA)结合,以产生有效的抗菌保护层。用于制作涂层的三种肽基多聚阳离子--聚(-精氨酸)(PAR)、聚(-赖氨酸)和聚(-鸟氨酸)--通过接触杀菌机制,对革兰氏阳性菌、革兰氏阴性菌和抗生素耐药菌提供了有效的抗菌屏障。此外,每条多阳离子链含有 30 个氨基酸残基的均聚多肽的活性更高,这说明多阳离子链的长度及其在涂层中的流动性对发挥接触杀灭抗菌特性的影响。然而,含 PAR 的涂层是三种所选聚合体中的最佳候选,因为它能促进细胞粘附和上皮单层的形成。它还能刺激内皮细胞产生一氧化氮,从而促进血管生成和随后的组织再生。更有趣的是,细菌对 PAR 没有产生抗药性,(PAR/HA)还能抑制真核病原体(如酵母菌)的增殖。此外,对植入兔子模型的(PAR/HA)涂层疝气网进行的研究证实,该涂层具有抗菌特性,但不会引起慢性炎症。这些令人印象深刻的协同作用凸显了 PAR/HA 涂层作为抗击细菌(包括对传统抗生素产生抗药性的细菌和与医疗器械相关的细菌)的重要工具的强大潜力。
期刊介绍:
Materials Today Bio is a multidisciplinary journal that specializes in the intersection between biology and materials science, chemistry, physics, engineering, and medicine. It covers various aspects such as the design and assembly of new structures, their interaction with biological systems, functionalization, bioimaging, therapies, and diagnostics in healthcare. The journal aims to showcase the most significant advancements and discoveries in this field. As part of the Materials Today family, Materials Today Bio provides rigorous peer review, quick decision-making, and high visibility for authors. It is indexed in Scopus, PubMed Central, Emerging Sources, Citation Index (ESCI), and Directory of Open Access Journals (DOAJ).