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Effective and biocompatible antibacterial surfaces via facile synthesis and surface modification of peptide polymers.

ABSTRACT: It is an urgent need to tackle drug-resistance microbial infections that are associated with implantable biomedical devices. Host defense peptide-mimicking polymers have been actively explored in recent years to fight against drug-resistant microbes. Our recent report on lithium hexamethyldisilazide-initiated superfast polymerization on amino acid N-carboxyanhydrides enables the quick synthesis of host defense peptide-mimicking peptide polymers. Here we reported a facile and cost-effective thermoplastic polyurethane (TPU) surface modification of peptide polymer (DLL: BLG = 90 : 10) using plasma surface activation and substitution reaction between thiol and bromide groups. The peptide polymer-modified TPU surfaces exhibited board-spectrum antibacterial property as well as effective contact-killing ability in vitro. Furthermore, the peptide polymer-modified TPU surfaces showed excellent biocompatibility, displaying no hemolysis and cytotoxicity. In vivo study using methicillin-resistant Staphylococcus aureus (MRSA) for subcutaneous implantation infectious model showed that peptide polymer-modified TPU surfaces revealed obvious suppression of infection and great histocompatibility, compared to bare TPU surfaces. We further explored the antimicrobial mechanism of the peptide polymer-modified TPU surfaces, which revealed a surface contact-killing mechanism by disrupting the bacterial membrane. These results demonstrated great potential of the peptide-modified TPU surfaces for practical application to combat bacterial infections that are associated with implantable materials and devices.

SUBMITTER: Lu Z

PROVIDER: S-EPMC8138731 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeDrug-eluting stents (DES) based on permanent polymeric coating matrices have been introduced to overcome the in stent restenosis associated with bare metal stents (BMS). A further step was the development of DES with biodegradable polymeric coatings to address the risk of thrombosis associated with first-generation DES. In this study we evaluate the biocompatibility of biodegradable polymer materials for their potential use as coating matrices for DES or as materials for fully bioabsorbable vascular stents.Materials and methodsFive different polymers, poly(L-lactide) PLLA, poly(D,L-lactide) PDLLA, poly(L-lactide-co-glycolide) P(LLA-co-GA), poly(D,L-lactide-co-glycolide) P(DLLA-co-GA) and poly(L-lactide-co-ε-caprolactone), P(LLA-co-CL) were examined in vitro without and with surface modification. The surface modification of polymers was performed by means of wet-chemical (NaOH and ethylenediamine (EDA)) and plasma-chemical (O2 and NH3) processes. The biocompatibility studies were performed on three different cell types: immortalized mouse fibroblasts (cell line L929), human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC). The biocompatibility was examined quantitatively using in vitro cytotoxicity assay. Cells were investigated immunocytochemically for expression of specific markers, and morphology was visualized using confocal laser scanning (CLSM) and scanning electron (SEM) microscopy. Additionally, polymer surfaces were examined for their thrombogenicity using an established hemocompatibility test.ResultsBoth endothelial cell types exhibited poor viability and adhesion on all five unmodified polymer surfaces. The biocompatibility of the polymers could be influenced positively by surface modifications. In particular, a reproducible effect was observed for NH3-plasma treatment, which enhanced the cell viability, adhesion and morphology on all five polymeric surfaces.ConclusionSurface modification of polymers can provide a useful approach to enhance their biocompatibility. For clinical application, attempts should be made to stabilize the plasma modification and use it for coupling of biomolecules to accelerate the re-endothelialization of stent surfaces in vivo.

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Effective and biocompatible antibacterial surfaces via facile synthesis and surface modification of peptide polymers.

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