1. ¹Department of Biomedical Engineering, SUNY at Stony Brook, Stony Brook, New York, USA
2. ²Department of Medicinal Chemistry and Center for Therapeutic Biomaterials, The University of Utah, Salt Lake City, Utah, USA
3. ³Department of Dermatology, SUNY at Stony Brook, Stony Brook, New York, USA
4. ⁴Department of Medicine, SUNY at Stony Brook, Stony Brook, New York, USA

Correspondence: Dr Richard A.F. Clark, Department of Biomedical Engineering, Dermatology and Medicine, HSC T-16, 060, SUNY Stony Brook, Stony Brook, New York 11794-8165, USA. E-mail: richard.clark@sunysb.edu

⁵These authors have contributed equally to this work.

Received 2 September 2005; Revised 13 February 2006; Accepted 7 March 2006; Published online 1 June 2006.

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.