Antimicrobial Peptide Dendrimers and Quorum-Sensing Inhibitors in Formulating Next-Generation Anti-Infection Cell Therapy Dressings for Burns

抗菌肽树枝状聚合物和群体感应抑制剂在配制下一代抗感染烧伤细胞治疗敷料中的应用

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作者:Paris Jafari, Alexandre Luscher, Thissa Siriwardena, Murielle Michetti, Yok-Ai Que, Laurence G Rahme, Jean-Louis Reymond, Wassim Raffoul, Christian Van Delden, Lee Ann Applegate, Thilo Köhler0

Abstract

Multidrug resistance infections are the main cause of failure in the pro-regenerative cell-mediated therapy of burn wounds. The collagen-based matrices for delivery of cells could be potential substrates to support bacterial growth and subsequent lysis of the collagen leading to a cell therapy loss. In this article, we report the development of a new generation of cell therapy formulations with the capacity to resist infections through the bactericidal effect of antimicrobial peptide dendrimers and the anti-virulence effect of anti-quorum sensing MvfR (PqsR) system compounds, which are incorporated into their formulation. Anti-quorum sensing compounds limit the pathogenicity and antibiotic tolerance of pathogenic bacteria involved in the burn wound infections, by inhibiting their virulence pathways. For the first time, we report a biological cell therapy dressing incorporating live progenitor cells, antimicrobial peptide dendrimers, and anti-MvfR compounds, which exhibit bactericidal and anti-virulence properties without compromising the viability of the progenitor cells.

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