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 ...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.展开更多
Contact-killing antimicrobial coatings based on host defense peptides(HDPs) and their synthetic mimics have shown potential as powerful tools to combat implant-associated infections. Covalent modification of the antim...Contact-killing antimicrobial coatings based on host defense peptides(HDPs) and their synthetic mimics have shown potential as powerful tools to combat implant-associated infections. Covalent modification of the antimicrobial surface has been utilized to prevent early-stage microbial infections owing to the less drug-leaching possibility that is beneficial to human health and the natural environment. Although considerable progress has been achieved in preparing contact-killing antimicrobial surfaces, discussions focusing on the in vitro and in vivo evaluations of these surfaces are limited. In this review, we summarized the established in vitro methods to simulate the practical interaction of microbes with the surrounding biological environment and the reported in vivo studies at different implant sites. We suggested that the in vivo specific site infection model is essential to gain a comprehensive understanding of these antimicrobial coatings in the preclinical stage, which can be established based on investigations performed using various in vitro assays and conventional non-specific site infection models. Overall, these precedent studies focusing on bacterial contact-killing coatings modified with HDPs and HDP mimics can be considered as critical to assess the surface antibacterial ability and to guide the future developments and applications of antimicrobial surfaces.展开更多
基金This research was supported by the National Natural Science Foundation of China(No.22075078,21774031)the National Key Research and Development Program of China(2016YFC1100401)+4 种基金Program of Shanghai Academic/Technology Research Leader(20XD1421400)State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,Donghua University,the Natural Science Foundation of Jiangsu Province(BK20180093)the Natural Science Foundation of Shanghai(18ZR1410300)Research program of State Key Laboratory of Bioreactor Engineering,the Fundamental Research Funds for the Central Universities(22221818014)The authors also thank Research Center of Analysis and Test of East China University of Science and Technology for the help on the characterization.
文摘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.
基金financially supported by the National Natural Science Foundation of China (Nos.21774031,21861162010and 21574038)the Clinical Research Plan of SHDC (No.SHDC2020CR4024)the Natural Science Foundation of Shanghai (No.18ZR1410300)。
文摘Contact-killing antimicrobial coatings based on host defense peptides(HDPs) and their synthetic mimics have shown potential as powerful tools to combat implant-associated infections. Covalent modification of the antimicrobial surface has been utilized to prevent early-stage microbial infections owing to the less drug-leaching possibility that is beneficial to human health and the natural environment. Although considerable progress has been achieved in preparing contact-killing antimicrobial surfaces, discussions focusing on the in vitro and in vivo evaluations of these surfaces are limited. In this review, we summarized the established in vitro methods to simulate the practical interaction of microbes with the surrounding biological environment and the reported in vivo studies at different implant sites. We suggested that the in vivo specific site infection model is essential to gain a comprehensive understanding of these antimicrobial coatings in the preclinical stage, which can be established based on investigations performed using various in vitro assays and conventional non-specific site infection models. Overall, these precedent studies focusing on bacterial contact-killing coatings modified with HDPs and HDP mimics can be considered as critical to assess the surface antibacterial ability and to guide the future developments and applications of antimicrobial surfaces.