A star-PEG-heparin hydrogel platform to aid cell replacement therapies for neurodegenerative diseases.
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.
Freudenberg
Uwe
U
Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), 01069 Dresden, Germany.
Hermann
Andreas
A
Welzel
Petra B
PB
Stirl
Katja
K
Schwarz
Sigrid C
SC
Grimmer
Milauscha
M
Zieris
Andrea
A
Panyanuwat
Woranan
W
Zschoche
Stefan
S
Meinhold
Dorit
D
Storch
Alexander
A
Werner
Carsten
C
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D055119:Elastic Modulus; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry; D006493:Heparin / Q000737:chemistry / Q000627:therapeutic use*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000627:therapeutic use*; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000628:therapy*; D009474:Neurons / Q000166:cytology; D009842:Oligopeptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000627:therapeutic use*; D011247:Pregnancy; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar
D009842:Oligopeptides; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D006493:Heparin