title: Production of heparin-functionalized hydrogels for the development of responsive and controlled growth factor delivery systems.
abstract: Methods to assemble polymeric hydrogels on the basis of noncovalent protein-glycosaminoglycan interactions have been previously demonstrated by us and others and hold promise in the development of receptor-responsive hydrogel materials; improvements in the mechanical properties of such systems would broaden their utility. Thus, in situ crosslinkable and degradable heparin-containing hydrogels were designed for the binding and controlled release of growth factors. Specifically, maleimide-functionalized high molecular weight heparin (HMWH) was synthesized via straightforward chemical methods that permitted facile and controllable modification of carboxylates in HMWH with maleimide groups via control of catalyst and reaction conditions, as assessed via 1H NMR spectroscopy. These modified heparins were crosslinked into hydrogels via reaction with various thiol-functionalized PEGs. The gelation times and elastic moduli of the gels, as assessed through oscillatory rheometry, could be tuned by controlling the functionality of HMWH, the concentration of the hydrogel, the identity of the PEG-based crosslinker, as well as the molar ratio between maleimide and thiol groups. The capability of the hydrogels to bind to growth factors was investigated with immunochemical assays. Preliminary studies indicate the controlled release of basic fibroblast growth factor (bFGF) from these materials and suggest their broader use in the design of responsive materials.
authors.affiliation: Department of Materials Science and Engineering, 201 DuPont Hall, University of Delaware, Newark, DE 19716, United States.
authors.forename: Ting
authors.initials: T
authors.lastname: Nie
authors.forename: Aaron
authors.initials: A
authors.lastname: Baldwin
authors.forename: Nori
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Kiick
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006493:Heparin / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D020100:Hydrogels; D008301:Maleimides / Q000737:chemistry; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D008301:Maleimides; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; C043592:maleimide; D006493:Heparin