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- Title
Molecular Stenting with a Crosslinked Hyaluronan Derivative Inhibits Collagen Gel Contraction.
- Authors
Mehra, Tanuj D.; Ghosh, Kaustabh; Xiao Zheng Shu; Prestwich, Glenn D.; Clark, Richard A. F.
- Abstract
Adult burn wounds, which lack hyaluronan (HA), often undergo excessive tissue remodeling and contraction. In contrast fetal wounds, which contain large amounts of HA, undergo remodeling that culminates in a scarless repair or regeneration. Therefore, adding a HA derivative to burn wounds would better mimic the fetal extracellular matrix and could reduce contraction. To test this hypothesis, we determined the effects of HA and its two derivatives on fibroblast-mediated, collagen gel contraction, an assay widely used to mimic in vivo wound contraction. Interestingly, high molecular weight HA (HMW HA) facilitated collagen gel contraction, whereas a thiol-functionalized derivative HA-DTPH weakly inhibited contraction. In contrast, polyethylene glycol diacrylate (PEGDA)-crosslinked HA-DTPH (HA-DTPH-PEGDA) strongly inhibited contraction in a concentration-dependent manner. Immunofluorescence staining of cellular actin showed that this inhibition was not owing to reduced cell attachment or spreading. Furthermore, the supernatant of contracted collagen-HMW HA gels contained greater amounts of HA than those found in the supernatant of collagen-HA-DTPH-PEGDA gels, suggesting that HMW HA facilitates contraction by effectively diffusing out of the collagen gels. Therefore, the results suggest that the crosslinking of HA-DTPH enhances the structural mechanics of collagen/HA-DTPH composites, which resists the fibroblast contractile forces and may, therefore, be able to reduce excessive wound contraction observed in pathological conditions.Journal of Investigative Dermatology (2006) 126, 2202–2209. doi:10.1038/sj.jid.5700380; published online 1 June 2006
- Subjects
COLLAGEN; CONNECTIVE tissues; EXTRACELLULAR matrix; TISSUE remodeling; FIBROBLASTS; HYALURONIC acid
- Publication
Journal of Investigative Dermatology, 2006, Vol 126, Issue 10, p2202
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/sj.jid.5700380