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bioRxiv · 10.1101/259481

Laminin heparin-binding peptides promiscuously bind growth factors and enhance diabetic wound healing

Ishihara, J.·Ishihara, A.·Fukunaga, K.·Briquez, P. S.·Hubbell, J. A.
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Abstract

Laminin, as a key component of the basement membrane extracellular matrix (ECM), regulates tissue morphogenesis. We show that multiple laminin isoforms promiscuously bind to growth factors (GFs) with high affinity, through their heparin binding domains (HBDs) located in the a chain LG domains. Interestingly, these domains also bind to syndecan cell-surface receptors, promoting attachment of fibroblasts and endothelial cells. We next explore application of these multifunctional laminin HBDs in skin healing in the type 2 diabetic mouse. We demonstrate that covalent incorporation of laminin HBDs into fibrin matrix enables the slow-release of GFs. Incorporation of the 33043-3067 laminin HBD significantly enhances in vivo wound-healing efficacy of vascular endothelial cell growth factor (VEGF)-A165 and platelet-derived growth factor (PDGF)-BB, under conditions where the GFs alone in fibrin are inefficacious. This laminin HBD peptide may be clinically useful by improving biomaterials as both GF reservoirs and cell scaffolds, leading to effective tissue regeneration.

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Ishihara, J., Ishihara, A., Fukunaga, K., Briquez, P. S., Hubbell, J. A.. 2018-02-05. Laminin heparin-binding peptides promiscuously bind growth factors and enhance diabetic wound healing. https://doi.org/10.1101/259481

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