There has been an increasing interest in understanding how the mechanical properties of the microenvironment influence stem cell fate. We describe studies of the proliferation and differentiation of neural stem cells (NSCs) encapsulated within three-dimensional scaffoldsalginate hydrogels -whose elastic moduli were varied over two orders of magnitude. The rate of proliferation of neural stem cells decreased with increase in the modulus of the hydrogels. Moreover, we observed the greatest enhancement in expression of the neuronal marker β-tubulin III within the softest hydrogels, which had an elastic modulus comparable to that of brain tissues. To our knowledge, this work represents the first demonstration of the influence of modulus on NSC differentiation in three-dimensional scaffolds. Three-dimensional scaffolds that control stem cell fate would be broadly useful for applications in regenerative medicine and tissue engineering.

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Hydrophobically modified alginate hydrogels have great potential in drug delivery as they are biologically compatible and cost efficient. While previous works have shown successful protein, and hydrophobic and hydrophilic drug delivery, little information regarding the relationship between crosslinker density and drug release rate is known. This paper investigates the impact of crosslinker density and hydrophobic degree of substitution within modified alginate gels and solutions on the release kinetics using model hydrophobic drug, sulindac. Near zero-order release was obtained for an extended period of 5 days. Drug release rates decreased as the crosslinker density within both modified alginate hydrogels and solutions increased. Release data fit well to a simplified Fickian relationship, suggesting that the release mechanism is diffusion-limited. These release characteristics also correlate with bulk rheological measurements, indicating a strong interrelationship between the mechanical properties and the drug release characteristics of the hydrogels.