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

Author

Listed:
  • Jun Ishihara

    (University of Chicago)

  • Ako Ishihara

    (University of Chicago)

  • Kazuto Fukunaga

    (University of Chicago
    Tokyo Institute of Technology)

  • Koichi Sasaki

    (University of Chicago
    Faculty of Engineering, Kyushu University)

  • Michael J. V. White

    (University of Chicago)

  • Priscilla S. Briquez

    (University of Chicago)

  • Jeffrey A. Hubbell

    (University of Chicago)

Abstract

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

Suggested Citation

  • Jun Ishihara & Ako Ishihara & Kazuto Fukunaga & Koichi Sasaki & Michael J. V. White & Priscilla S. Briquez & Jeffrey A. Hubbell, 2018. "Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04525-w
    DOI: 10.1038/s41467-018-04525-w
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    Cited by:

    1. Lianghui Cheng & Zhiyong Zhuang & Mingming Yin & Yuan Lu & Sujuan Liu & Minle Zhan & Liyuan Zhao & Zhenyan He & Fanling Meng & Sidan Tian & Liang Luo, 2024. "A microenvironment-modulating dressing with proliferative degradants for the healing of diabetic wounds," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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