(567b) Hydrolytically Degradable Affinity PEG Hydrogel Scaffolds for Neural Stem Cell Delivery

Cell fate is determined by cell-cell interactions as well as response to soluble and matrix molecules in the cellular microenvironment. The decision of neural/glial fate is made during the last cell cycle of neural stem cells (NSC) in the proliferative zones of the brain1. Multiple cell-secreted molecules, e.g., epidermal growth factor, fibroblast growth factor and hepatocyte growth factor (HGF), control NSC proliferation2-4. HGF exhibits multiple activities in both neural5 and nonneural tissues6 in a precise concentration and cell cycle dependent manner; thus because of their powerful effects, we hypothesize that the precise presentation, release rate and concentration of these factors are required in order to control cell response. Three-dimensional hydrolytically-degradable polyethylene glycol (PEG) hydrogels were designed and were based on the selective cross-linking between 4-arm PEG-vinyl sulfone backbone and PEG-dithiol cross-linkers7. Our previous work demonstrated that the PEG hydrogels had tunable mechanical properties (i.e., shear modulus, degradation rate) and showed great potential for use as cell culture scaffolds as well as implantable scaffolds for stem cell therapies. In this work, we explored several approaches for presenting HGF in this 3D gel with the ultimate goal of determining which approach best promotes NSC proliferation and differentiation to the glial fate. New cross-linkers, thiolated heparin and peptide sequences with affinity to HGF were synthesized, used in conjunction with the PEG-based hydrogels and applied to NSC culture. This work provides a novel basis to present and control the release of key soluble factors through a highly tunable 3D hydrogel matrix to control NPC viability and differentiation.

 References:

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5. F Maina, et al. Neuron 1998 20:835.   6. Y Liu, et al. Kidney Int 1999 55:442   7. Zustiak S, et al. Biomacromol 2010 11:134