Polysaccharide-poly(ethylene glycol) star copolymer as a scaffold for the production of bioactive hydrogels.
The production of polysaccharide-derivatized surfaces, polymers, and biomaterials has been shown to be a useful strategy for mediating the biological properties of materials, owing to the importance of polysaccharides for the sequestration and protection of bioactive proteins in vivo. We have therefore sought to combine the benefits of polysaccharide derivatization of polymers with unique opportunities to use these polymers for the production of bioactive, noncovalently assembled hydrogels. Accordingly, we report the synthesis of a heparin-modified poly(ethylene glycol) (PEG) star copolymer that can be used in the assembly of bioactive hydrogel networks via multiple strategies and that is also competent for the delivery of bioactive growth factors. A heparin-decorated polymer, synthesized by the reaction of thiol end-terminated four-arm star PEG (M(n) = 10 000) with maleimide functionalized low molecular weight heparin (LMWH, M(r) = 3000), has been characterized via (1)H NMR spectroscopy and size-exclusion chromatography; results indicate attachment of the LMWH with at least 73% efficiency. Both covalently and noncovalently assembled hydrogels can be produced from the PEG-LMWH conjugate. Viscoelastic noncovalently assembled hydrogels have been formed on the basis of the interaction of the PEG-LMWH with a PEG polymer bearing multiple heparin-binding peptide motifs. The binding and release of therapeutically important proteins from the assembled hydrogels have also been demonstrated via immunochemical assays, which demonstrate the slow release of basic fibroblast growth factor (bFGF) as a function of matrix erosion. The combination of these results suggests the opportunities for producing polymer-polysaccharide conjugates that can assemble into novel hydrogel networks on the basis of peptide-saccharide interactions and for employing these materials in delivery applications.
Yamaguchi
Nori
N
Department of Materials Science and Engineering and Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19716, USA.
Kiick
Kristi L
KL
D000595:Amino Acid Sequence; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D020100:Hydrogels; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*
D020100:Hydrogels; D011134:Polysaccharides; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols