Synthetic hydrogels can closely mimic the cell-instructive characteristics of extracellular matrices surrounding cells in natural tissues. Using such materials, advances in three-dimensional cell culture techniques over the past decade rely on the increasingly complex recapitulation of cellular in vivo microenvironments. In particular, mimicking both biomolecular and physical features of extracellular matrix structures is of great interest for many fields of cell biology and biomedicine.
As a current challenge, the modulation of consecutive biochemical and mechanical triggers of cell fate decisions in synthetic materials requires novel techniques. Towards this aim, Tsurkan et al. report a light-sensitive multi-component hydrogel material capable of both photoclevable and enzymatic degradation and demonstrate how the material can be utilized to direct the fate of neural precursor cells in vitro. The material consists of heparin, which can complex and present various morphogens for cell signaling, and poly(ethylene glycol)-peptide conjugates, which contain matrix metalloproteinase- and photo-sensitive modules. The introduced design allows for localized, light-directed degradation for modulating spatial constraints produced by the hydrogel matrix and can be additionally reorganized locally by cellular activity through secreted proteases. Moreover, the specific approach developed within the reported study enabled the formation of multilayer materials containing a strong biofunctional contrast between the cell-adhesive bottom and the non-adhesive walls of hydrogel-based microwells and channels. The resulting compartments were applied in the culture neural precursor cells, revealing that the cells form neurospheres in cylindrical compartments but adopt a linear morphology within hydrogel-based channels.
Taken together, the described approach offers a simple method for creating various matrix architectures with defined biochemical functionalities, allowing researchers to easily generate different variants of cell microenvironments to systematically explore the interplay of exogenous cues on growth and differentiation of cells in culture.
