Forum for Nordic Dermato-Venereology Nr 4, 2019 | Página 28

Highlight from Nordic Scientific Papers
wound healing
–
new treatment
Researchers in Lund have developed a treating gel using natural mechanisms to prevent and treat wound infections. This study has been
published in Science Translational Medicine and has already been highly noticed.
A dual-action peptide-containing hydrogel targets wound infection and inflammation.
Puthia M, Butrym M, Petrlova J, Strömdahl AC, Andersson MÅ, Kjellström S, Schmidtchen A
Abstract
There is a clinical need for improved wound treatments that prevent both infection and excessive inflammation. TCP-25, a
thrombin-derived peptide, is antibacterial and scavenges pathogen-associated molecular patterns (PAMPs), such as lipopoly-
saccharide, thereby preventing CD14 interaction and Toll-like receptor dimerization, leading to reduced downstream immune
activation. Here, we describe the development of a hydrogel formulation that was functionalized with TCP-25 to target bacteria
and associated PAMP-induced inflammation. In vitro studies determined the polymer prerequisites for such TCP-25-mediated
dual action, favoring the use of noncharged hydrophilic hydrogels, which enabled peptide conformational changes and LPS
binding. The TCP-25-functionalized hydrogels killed Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas
aeruginosa bacteria in vitro, as well as in experimental mouse models of subcutaneous infection. The TCP-25 hydrogel also
mediated reduction of LPS-induced local inflammatory responses, as demonstrated by analysis of local cytokine production
and in vivo bioimaging using nuclear factor κB (NF-κB) reporter mice. In porcine partial thickness wound models, TCP-25
prevented infection with S. aureus and reduced concentrations of proinflammatory cytokines. Proteolytic fragmentation of
TCP-25 in vitro yielded a series of bioactive TCP fragments that were identical or similar to those present in wounds in vivo.
Together, the results demonstrate the therapeutic potential of TCP-25 hydrogel, a wound treatment based on the body’s
peptide defense, for prevention of both bacterial infection and the accompanying inflammation.
Sci Transl Med. 2020 Jan 1;12(524). pii: eaax6601. doi: 10.1126/scitranslmed.aax6601.
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