Overexpression of Lysyl Oxidase to Increase Matrix Crosslinking and Improve Tissue Strength in Dermal Wound Healing

TitleOverexpression of Lysyl Oxidase to Increase Matrix Crosslinking and Improve Tissue Strength in Dermal Wound Healing
Publication TypeJournal Article
Year of Publication2006
AuthorsLau, Y-KI, Gobin, AM, West, JL
JournalAnnals of Biomedical Engineering
Volume34
Issue8
Pagination1239 - 1246
Date Published8/2006
ISSN1573-9686
Keywordsgene therapy; mechanical strength; wound healing
Abstract

In this study, we aimed to increase crosslinking in collagen and elastin in the extracellular matrix through overexpression of lysyl oxidase (LO) in order to improve mechanical strength in dermal wounds during healing. We had used a gene activated matrix (GAM) approach to locally deliver plasmid DNA (pDNA) complexed with polyethylenimine (PEI) in collagen gels at the wound site for localized and sustained transfection of cells involved in the healing process. We first demonstrated in vitro that PEI-pDNA complexes in collagen gels could be taken up and expressed by cultured fibroblasts for at least 20 days. In vitro studies showed that fibroblast-seeded GAMs with the LO transgene exhibited over a 3-fold increase in mechanical strength as compared with a green fluorescent protein (GFP)-transgene control. Addition of an inhibitor of LO abolished this increase. We applied this system in a rat dermal wound healing model and showed that treatment with LO-producing GAMs led to significantly enhanced mechanical strength of the wound site.

DOI10.1007/s10439-006-9130-8
Short TitleAnn Biomed Eng
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