title: Enzymatic degradation of heparin-modified hydrogels and its effect on bioactivity.
abstract: The extracellular matrix is continually remodelled by the action of various enzymes such as heparanase, which specifically targets heparan sulfate (HS) and is found in human platelets at high levels. The activity of heparin-containing hydrogels following incubation with platelet extract (PE) was investigated in order to simulate the responses that might occur when the hydrogels, as tissue engineered scaffolds, come in contact with blood products at the site of an injury. The heparanase activity of PE on heparin, used as a model of HS, was confirmed by the decrease in molecular weight. PE treatment diminished heparin's anticoagulation property but increased its FGF-2 signalling activity, suggesting that the PE's heparanase activity cleaves at the 3-O-sulfated glucosamine to produce large fragments that can signal cell receptors. The dual effect observed when poly(vinyl alcohol)/heparin co-hydrogels were incubated with PE supports the hypothesis of platelets having the capacity to limit anticoagulation and thus promote blood clot formation, which may be critical in the process of tissue repair.
authors.affiliation: Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia. anastasia.nilasaroya@health.wa.gov.au
authors.forename: Anastasia
authors.initials: A
authors.lastname: Nilasaroya
authors.forename: Penny J
authors.initials: PJ
authors.lastname: Martens
authors.forename: John M
authors.initials: JM
authors.lastname: Whitelock
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D005966:Glucuronidase / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology*; D008422:Materials Testing; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006493:Heparin; D020100:Hydrogels; D000099175:Heparanase