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Fibronectin‐derived Epiviosamines enhance PDGF‐BB‐stimulated human dermal fibroblast migration in vitro and granulation tissue formation in vivo
Author(s) -
Prasad Atulya,
Lin Fubao,
Clark Richard A. F.
Publication year - 2019
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12744
Subject(s) - fibronectin , granulation tissue , in vivo , fibroblast , in vitro , chemistry , platelet derived growth factor receptor , microbiology and biotechnology , dermal fibroblast , wound healing , immunology , extracellular matrix , biology , biochemistry , growth factor , receptor
ABSTRACT Fibronectin (FN) is a multimodular 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 600 μM 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.