Heparin functionalized PEG gels that modulate protein adsorption for hMSC adhesion and differentiation.
Heparin was modified with methacrylate groups, copolymerized with dimethacrylated poly(ethylene glycol), and analyzed as a localized delivery vehicle for bFGF and synthetic extracellular matrix for the differentiation of hMSCs. By deriving cues from molecules normally present in the extracellular matrix (ECM), a complex network of collagens, laminin, fibronectin, glycosaminoglycans, and growth factors, synthetic cell scaffolds can be designed that actively sequester important bioactive signals. Among the glycosaminoglycans, heparin binds reversibly with many proteins, therefore, poly(ethylene glycol) based biomaterials, normally resistant to cell adhesion, functionalized with heparin in order to sequester important proteins, can actively and selectively stimulate desired cell functions. Results demonstrate that methacrylate-modified heparin retained its ability to bind heparin-binding proteins both in solution and when copolymerized with dimethacrylated PEG in a hydrogel. In addition, the heparin functionalized gels can deliver biologically active bFGF for up to 5 weeks. Finally, the gels were examined as a potential scaffold for hMSC culture and were found to promote adhesion, proliferation, and osteogenic differentiation.
Benoit
Danielle S W
DS
Department of Chemical and Biological Engineering, University of Colorado, Boulder, 80309-0424, USA.
Anseth
Kristi S
KS
D000327:Adsorption; D001672:Biocompatible Materials / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry; D005782:Gels / Q000737:chemistry; D006493:Heparin / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D011092:Polyethylene Glycols / Q000737:chemistry*; D011485:Protein Binding; D023822:Tissue Engineering / Q000379:methods*
D001672:Biocompatible Materials; D005782:Gels; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols; D006493:Heparin