A star-PEG–heparin hydrogel platform to aid cell replacement therapies for neurodegenerative diseases

• Published in: Biomaterials Vol. 30; no. 28; pp. 5049 - 5060
• Main Authors: Freudenberg, Uwe, Hermann, Andreas, Welzel, Petra B, Stirl, Katja, Schwarz, Sigrid C, Grimmer, Milauscha, Zieris, Andrea, Panyanuwat, Woranan, Zschoche, Stefan, Meinhold, Dorit, Storch, Alexander, Werner, Carsten
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-10-2009
• Subjects: Advanced Basic Science; Animals; Biohybrid material; Cell replacement/implantation; Cell Survival; Cells, Cultured; Dentistry; Elastic Modulus; Embryonic Stem Cells - cytology; Female; Fibroblast Growth Factor 2 - chemistry; Heparin - chemistry; Heparin - therapeutic use; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogel, Polyethylene Glycol Dimethacrylate - therapeutic use; Mesencephalon - cytology; Mice; Mice, Inbred C57BL; Neural stem cells; Neurodegenerative Diseases - therapy; Neurons - cytology; Oligopeptides - chemistry; Polyethylene Glycols - chemistry; Polyethylene Glycols - therapeutic use; Pregnancy; Prostheses and Implants; Rats; Rats, Wistar; Neural stem cells; Biohybrid material; Cell replacement/implantation
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2009.06.002

Abstract Biofunctional matrices for in vivo tissue engineering strategies must be modifiable in both biomolecular composition and mechanical characteristics. To address this challenge, we present a modular system of biohybrid hydrogels based on covalently cross-linked heparin and star-shaped poly(ethylene glycols) (star-PEG) in which network characteristics can be gradually varied while heparin contents remain constant. Mesh size, swelling and elastic moduli were shown to correlate well with the degree of gel component cross-linking. Additionally, secondary conversion of heparin within the biohybrid gels allowed the covalent attachment of cell adhesion mediating RGD peptides and the non-covalent binding of soluble mitogens such as FGF-2. We applied the biohybrid gels to demonstrate the impact of mechanical and biomolecular cues on primary nerve cells and neural stem cells. The results demonstrate the cell type-specific interplay of synergistic signaling events and the potential of biohybrid materials to selectively stimulate cell fate decisions. These findings suggest important future uses for this material in cell replacement based-therapies for neurodegenerative diseases.