Anti-Microbial Dendrimers against Multidrug-Resistant P. aeruginosa Enhance the Angiogenic Effect of Biological Burn-wound Bandages

Abstract

Multi-drug resistant Pseudomonas aeruginosa has increased progressively and impedes further regression in mortality in burn patients. Such wound infections serve as bacterial reservoir for nosocomial infections and are associated with significant morbidity and costs. Anti-microbial polycationic dendrimers G3KL and G3RL, able to kill multi-drug resistant P. aeruginosa, have been previously developed. The combination of these dendrimers with a class of biological bandages made of progenitor skin cells, which secrete growth factors, could positively impact wound-healing processes. However, polycations are known to be used as anti-angiogenic agents for tumor suppression. Since, neovascularization is pivotal in the healing of deep burn-wounds, the use of anti-microbial dendrimers may thus hinder the healing processes. Surprisingly, we have seen in this study that G3KL and G3RL dendrimers can have angiogenic effects. Moreover, we have shown that a dendrimer concentration ranging between 50 and 100 μg/mL in combination with the biological bandages can suppress bacterial growth without altering cell viability up to 5 days. These results show that antimicrobial dendrimers can be used in combination with biological bandages and could potentially improve the healing process with an enhanced angiogenesis.

Lipidated Peptide Dendrimers Killing Multidrug-Resistant Bacteria

“…[25][26][27] Extending on previous reports that multivalent display of AMPs on a poly-lysine tree can increase their antimicrobial activity, [28][29][30] we recently identified the third generation (G3) antimicrobial peptide dendrimer (AMPD) G3KL consisting of a lysine-leucine dipeptide repeated across the dendrimer branches active against P. aeruginosa and A. baumannii laboratory strains, 31 as well as against a broad panel of multidrug resistant clinical isolates of both of these pathogens, 32 and with favorable pro-angiogenic properties in biological burn-wound bandages. 33 We had initially obtained G3KL by exploiting a dendritic effect on antimicrobial activity, i.e. an increase in antibacterial activity with dendrimer generation, with the consequence that G3KL…”

Adaptive and Mutational Responses to Peptide Dendrimer Antimicrobials in Pseudomonas aeruginosa

“…G3KL and its derivatives are synthesized with D-amino acids conferring increased stability against proteolytic cleavage in the presence of human serum (21). Furthermore, G3KL was shown to have an angiogenic effect on injured human fibroblast cells (24). G3KL-like dendrimers are currently under preclinical development.…”

Nanotechnology-Driven Therapeutic Interventions in Wound Healing: Potential Uses and Applications

“…100 For instance, gelatin–dendrimer nanofibers were generated via electrospinning and treated the blends with polyethylene glycol (PEG) to form semi-interpenetrating networks (sIPNs). 101 Silver was incorporated within the sIPNs network to add antibacterial properties to the network.…”