title: Anti-endotoxic and antibacterial effects of a dermal substitute coated with host defense peptides.
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.
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Biomedical Center, Tornavägen 10, SE-22184 Lund, Sweden; Division of Respiratory Medicine and Allergology, Department of Clinical Sciences, Lund University, Biomedical Center, Tornavägen 10, SE-22184 Lund, Sweden. Electronic address: gopinath.kasetty@med.lu.se.
authors.forename: Gopinath
authors.initials: G
authors.lastname: Kasetty
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Biomedical Center, Tornavägen 10, SE-22184 Lund, Sweden.
authors.forename: Martina
authors.initials: M
authors.lastname: Kalle
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Biomedical Center, Tornavägen 10, SE-22184 Lund, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.affiliation: Deutsches Institut für Zell- und Gewebeersatz gGmbH, Berlin, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Brune
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Biomedical Center, Tornavägen 10, SE-22184 Lund, Sweden; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore.
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D017768:Skin, Artificial; D013917:Thrombin / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D004731:Endotoxins; D010455:Peptides; D013917:Thrombin
keywords: Antimicrobial; Epiflex; Host defense peptides; Human acellular dermis; Inflammation