Institute for Molecular Engineering, University of Chicago, Chicago, IL, 60637, USA.
Department of Bioengineering, Tokyo Institute of Technology, 226-8501, Yokohama, Kanagawa, Japan.
Nat Commun. 2018 Jun 4;9(1):2163. doi: 10.1038/s41467-018-04525-w.
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.
层粘连蛋白作为基底膜细胞外基质 (ECM) 的关键组成部分，调节组织形态发生。在这里，我们表明多种层粘连蛋白同工型通过其位于 α 链层粘连蛋白 G (LG) 结构域中的肝素结合结构域 (HBD) 与高亲和力的生长因子 (GFs) 随意结合。这些结构域还与连接蛋白细胞表面受体结合，促进成纤维细胞和内皮细胞的附着。我们探索了这些多功能层粘连蛋白 HBD 在 2 型糖尿病小鼠伤口愈合中的应用。我们证明，将层粘连蛋白 HBD 共价掺入纤维蛋白基质中可提高 GFs 的保留率，并显著增强血管内皮细胞生长因子 (VEGF-A165) 和血小板衍生生长因子 (PDGF-BB) 在体内促进伤口愈合的功效，而在纤维蛋白中单独使用 GFs 则无效。这种层粘连蛋白 HBD 肽通过改善生物材料基质作为 GF 储库和细胞支架的功能，可能具有临床应用价值，从而实现有效的组织再生。
