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Sökning: id:"swepub:oai:lup.lub.lu.se:a0f85c35-9cc4-40a0-b404-2d6c0ef6c50b" > A dual-action pepti...

A dual-action peptide-containing hydrogel targets wound infection and inflammation

Puthia, Manoj (författare)
Lund University,Lunds universitet,Schmidtchen lab,Forskargrupper vid Lunds universitet,Schmidtchen Lab,Lund University Research Groups,Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden
Butrym, Marta (författare)
Lund University,Lunds universitet,Dermatologi och venereologi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Dermatology and Venereology (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden
Petrlova, Jitka (författare)
Lund University,Lunds universitet,Schmidtchen lab,Forskargrupper vid Lunds universitet,Schmidtchen Lab,Lund University Research Groups,Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden
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Strömdahl, Ann Charlotte (författare)
Lund University,Lunds universitet,Schmidtchen lab,Forskargrupper vid Lunds universitet,Schmidtchen Lab,Lund University Research Groups,Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden
Andersson, Madelene (författare)
In2cure AB, Medicon Village, SE-22381 Lund, Sweden
Kjellström, Sven (författare)
Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Lund University, SE-22362 Lund, Sweden
Schmidtchen, Artur (författare)
Lund University,Lunds universitet,Schmidtchen lab,Forskargrupper vid Lunds universitet,Schmidtchen Lab,Lund University Research Groups,Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-22184 Lund, Sweden; Copenhagen Wound Healing Center, Bispebjerg Hospital, Department of Biomedical Sciences, University of Copenhagen, DK-2400 Copenhagen, Denmark; Dermatology, Skåne University Hospital, SE-22185 Lund, Sweden,Bispebjerg Hospital,Skåne University Hospital
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 (creator_code:org_t)
American Association for the Advancement of Science (AAAS), 2020
2020
Engelska.
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 12:524
Relaterad länk:
http://dx.doi.org/10...
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https://mau.diva-por... (primary) (Raw object)
https://lup.lub.lu.s...
https://doi.org/10.1...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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 lipopolysaccharide, 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)
NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

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