ABSTRACT

Extracellular glycans, such as glycosaminoglycans (GAGs), provide an essential regulatory component during the development and maintenance of tissues. GAGs, which harbor binding sites for a range of growth factors and other morphogens, help establish gradients of these molecules in the extracellular matrix (ECM) and promote the formation of active signaling complexes when presented at the cell surface. As such, GAGs have been pursued as biologically active components for the development of biomaterials for cell-based regenerative therapies. However, their structural complexity and compositional heterogeneity make establishing structure-function relationships for this class of glycans difficult. Here, we describe a stem cell array platform, in which GAG polysaccharides are conjugated to adhesion proteins and introduced into a polyacrylamide hydrogel network to directly measure their contributions to the activation of growth factor signaling pathways in cells. With the recent emergence of powerful synthetic and recombinant technologies to produce well-defined GAG structures, a platform for analyzing both growth factor binding and signaling in response to the presence of these biomolecules will provide a powerful tool for integrating glycans into biomaterials to advance their biological properties and applications.

Abstract Figure

The present study describes the integration of glycosaminoglycan-protein conjugates into a hydrogel-supported stem cell microarray platform to analyze the activity of extracellular glycans in growth factor signaling. Such platforms can enable rapid development and optimization of functional glycomaterials for stem cell-based regenerative therapies.