We report here structure-property relationship between linear and branched polyethylene imines by examining
their antimicrobial activities against wide range of pathogens. Both
the polymers target
the cytoplasmic membrane of bacteria and yeasts, eliciting rapid microbicidal properties. Using multiscale molecular dynamic simulations, we showed that, in both fully or partially protonated forms LPEI discriminates between mammalian and bacterial model membranes whereas BPEI lacks selectivity for both
the model membranes. Simulation results suggest that LPEI forms weak complex with
the zwitterionic lipids whereas
the side chain amino groups of BPEI sequester
the zwitterionic lipids by forming tight complex. Consistent with
these observations, label-free cell impedance measurements, cell viability assays and high content analysis indicate that BPEI is cytotoxic to human epi
thelial and fibroblasts cells. Crosslinking of BPEI onto electrospun gelatin mats attenuate
the cytotoxicity for fibroblasts while retaining
the antimicrobial activity against Gram-positive and yeasts strains. PEI crosslinked gelatin mats elicit bactericidal activity by contact-mediated killing and durable to leaching for 7 days. The potent antimicrobial activity combined with enhanced selectivity of
the crosslinked ES gelatin mats would expand
the arsenel of biocides in
the management of superficial skin infections. The contact-mediated microbicidal properties may avert antimicrobial resistance and expand
the diversity of applications to prevent microbial contamination.
Statement of Significance
Current commercially available advanced wound dressings are either impregnated with metallic silver or silver salts which have side effects or may not avert antimicrobial resistance. In this article, we have used multidisciplinary approach comprising of computational, chemical and biological methods to understand the antimicrobial properties and biocompatibility of linear (LPEI) and branched (BPEI) polyethylenimines. We then applied this knowledge to develop dual purpose wound dressings containing these polymers, which encourages healing while maintain antimicrobial activity. In addition, the approach can be expanded to rationalize the antimicrobial vs. cytotoxicity of other cationic polymers and the method of crosslinking would enhance their potentials as biocides for advanced materials.