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Eur J Pharm Biopharm. 2014 Feb;86(2):277-83. doi: 10.1016/j.ejpb.2013.10.003. Epub 2013 Oct 15.

Wound healing potential of a dimeric InlB variant analyzed by in vitro experiments on re-epithelialization of human skin models.

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Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, Germany.
Department of Molecular Structural Biology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
Department of Chemistry and Center for Biotechnology (CeBiTec), Bielefeld University, Bielefeld, Germany.
Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, Germany. Electronic address:


A constitutively dimeric truncated variant of internalin B (InlB321-CD), acting as stimulator of the receptor tyrosine kinase MET, was tested for dermal wound-healing potential. Due to a lack of the endogenous MET agonist HGF/SF in chronic wounds, HGF/SF substitution by an InlB321-CD-loaded hydrogel might be beneficial in chronic wound therapy. In this study, InlB321-CD in solution and incorporated in a hydrogel was tested for mitogenic effects on immortalized human dermal keratinocytes (HaCaT) with an MTT assay. Cell migration was investigated with a scratch assay on primary keratinocytes (PHK) and on HaCaT. For the latter, scratching needed to be mitomycin C-controlled. InlB321-CD effects on a model of human skin were analyzed histologically with respect to viability. InlB321-CD led to dose-dependent proliferative effects on HaCaT cells whereas the equimolar dose of monomeric InlB321 did not. Upon hydrogel incorporation of InlB321-CD its mitogenic activity for HaCaT cells was maintained thus confirming the hydrogel as a promising drug delivery system. Motogenic effects were shown on both HaCaT and PHK cells. InlB321-CD neither possesses cytotoxic effects on the viability of a human skin model nor alters its organotypic cell morphology.


3D skin model; Hydrogel; Internalin B; Keratinocyte; MET receptor; MTT assay; Migration; Proliferation; Scratch assay; Wound healing

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