Fibronectin‐derived Epiviosamines enhance PDGF‐BB‐stimulated human dermal fibroblast migration in vitro and granulation tissue formation in vivo
Atulya Prasad Ph. D.  Fubao Lin Ph. D.  Richard A F Clark MD
First published: 20 June 2019 https://doi.org/10.1111/wrr.12744
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/wrr.12744.
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ABSTRACT
Fibronectin (FN) is a multi‐modular glycoprotein that is a critical component of the extracellular matrix (ECM) anlage during embryogenesis, morphogenesis, and wound repair. Our laboratory has previously described a family of FN‐derived peptides collectively called ‘Epiviosamines’ that enhance platelet‐derived growth factor‐BB (PDGF‐BB)‐driven tissue cell survival, speed burn healing, and reduce scarring. In this study, we used an agarose drop outmigration assay to report that Epiviosamines can enhance PDGF‐BB‐stimulated adult human dermal fibroblast (AHDF) outmigration in a dose‐dependent manner. Furthermore, these peptides can, when delivered topically, stimulate granulation tissue formation in vivo. A thiol‐derivatized hyaluronan hydrogel cross‐linked with polyethyleneglycol diacrylate (PEGDA) was used to topically deliver a cyclized Epiviosamine: cP12 and a cyclized engineered variant of cP12 termed cNP8 to porcine, full‐thickness, excisional wounds. Both cP12 and cNP8 exhibited dose‐dependent increases in granulation tissue formation at day 4, with 600μM cNP8 significantly enhancing new granulation tissue compared to vehicle alone. In contrast to previous studies, this study suggests that Epiviosamines can be used to increase granulation tissue formation without an exogenous supply of PDGF‐BB or any cell‐binding peptides. Thus, Epiviosamine may be useful topically to increase granulation tissue formation in acute wounds.