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

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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.

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ACKNOWLEDGMENTS

Research funding was provided by National Institutes of Health (RO1HL-60485).

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Authors and Affiliations

  1. Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX, USA

    Ying-Ka Ingar Lau, Andre M. Gobin & Jennifer L. West

  2. Department of Bioengi-neering, Rice University, P.O. Box 1892, MS-142, Houston, TX, USA, 77251-1892

    Jennifer L. West

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  1. Ying-Ka Ingar Lau
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  2. Andre M. Gobin
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Correspondence to Jennifer L. West.

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Lau, YK.I., Gobin, A.M. & West, J.L. Overexpression of Lysyl Oxidase to Increase Matrix Crosslinking and Improve Tissue Strength in Dermal Wound Healing. Ann Biomed Eng 34, 1239–1246 (2006). https://doi.org/10.1007/s10439-006-9130-8

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