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Anti-endotoxic and antibacterial effects of a dermal substitute coated with host defense peptides.

Kasetty, Gopinath LU ; Kalle, Martina LU ; Mörgelin, Matthias LU ; Brune, Jan Claas LU and Schmidtchen, Artur LU (2015) In Biomaterials 53. p.415-425
Abstract
Biomaterials used during surgery and wound treatment are of increasing importance in modern medical care. In the present study we set out to evaluate the addition of thrombin-derived host defense peptides to human acellular dermis (hAD, i.e. epiflex(®)). Antimicrobial activity of the functionalized hAD was demonstrated using radial diffusion and viable count assays against Gram-negative Escherichia coli, Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacteria. Electron microscopy analyses showed that peptide-mediated bacterial killing led to reduced hAD degradation. Furthermore, peptide-functionalized hAD displayed endotoxin-binding activity in vitro, as evidenced by inhibition of NF-κB activation in human monocytic cells... (More)
Biomaterials used during surgery and wound treatment are of increasing importance in modern medical care. In the present study we set out to evaluate the addition of thrombin-derived host defense peptides to human acellular dermis (hAD, i.e. epiflex(®)). Antimicrobial activity of the functionalized hAD was demonstrated using radial diffusion and viable count assays against Gram-negative Escherichia coli, Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacteria. Electron microscopy analyses showed that peptide-mediated bacterial killing led to reduced hAD degradation. Furthermore, peptide-functionalized hAD displayed endotoxin-binding activity in vitro, as evidenced by inhibition of NF-κB activation in human monocytic cells (THP-1 cells) and a reduction of pro-inflammatory cytokine production in whole blood in response to lipopolysaccharide stimulation. The dermal substitute retained its anti-endotoxic activity after washing, compatible with results showing that the hAD bound a significant amount of peptide. Furthermore, bacteria-induced contact activation was inhibited by peptide addition to the hAD. E. coli infected hAD, alone, or after treatment with the antiseptic substance polyhexamethylenebiguanide (PHMB), yielded NF-κB activation in THP-1 cells. The activation was abrogated by peptide addition. Thus, thrombin-derived HDPs should be of interest in the further development of new biomaterials with combined antimicrobial and anti-endotoxic functions for use in surgery and wound treatment. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biomaterials
volume
53
pages
415 - 425
publisher
Elsevier
external identifiers
  • pmid:25890739
  • wos:000353929800039
  • scopus:84927938090
ISSN
1878-5905
DOI
10.1016/j.biomaterials.2015.02.111
language
English
LU publication?
yes
id
9cc1215b-5d8c-40dc-8919-025bc4ce0aff (old id 5341307)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25890739?dopt=Abstract
date added to LUP
2015-05-05 08:15:14
date last changed
2017-05-28 03:14:22
@article{9cc1215b-5d8c-40dc-8919-025bc4ce0aff,
  abstract     = {Biomaterials used during surgery and wound treatment are of increasing importance in modern medical care. In the present study we set out to evaluate the addition of thrombin-derived host defense peptides to human acellular dermis (hAD, i.e. epiflex(®)). Antimicrobial activity of the functionalized hAD was demonstrated using radial diffusion and viable count assays against Gram-negative Escherichia coli, Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacteria. Electron microscopy analyses showed that peptide-mediated bacterial killing led to reduced hAD degradation. Furthermore, peptide-functionalized hAD displayed endotoxin-binding activity in vitro, as evidenced by inhibition of NF-κB activation in human monocytic cells (THP-1 cells) and a reduction of pro-inflammatory cytokine production in whole blood in response to lipopolysaccharide stimulation. The dermal substitute retained its anti-endotoxic activity after washing, compatible with results showing that the hAD bound a significant amount of peptide. Furthermore, bacteria-induced contact activation was inhibited by peptide addition to the hAD. E. coli infected hAD, alone, or after treatment with the antiseptic substance polyhexamethylenebiguanide (PHMB), yielded NF-κB activation in THP-1 cells. The activation was abrogated by peptide addition. Thus, thrombin-derived HDPs should be of interest in the further development of new biomaterials with combined antimicrobial and anti-endotoxic functions for use in surgery and wound treatment.},
  author       = {Kasetty, Gopinath and Kalle, Martina and Mörgelin, Matthias and Brune, Jan Claas and Schmidtchen, Artur},
  issn         = {1878-5905},
  language     = {eng},
  pages        = {415--425},
  publisher    = {Elsevier},
  series       = {Biomaterials},
  title        = {Anti-endotoxic and antibacterial effects of a dermal substitute coated with host defense peptides.},
  url          = {http://dx.doi.org/10.1016/j.biomaterials.2015.02.111},
  volume       = {53},
  year         = {2015},
}