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Stem Cell Microarrays for Assessing Growth Factor Signaling in Engineered Glycan Microenvironments
Author(s) -
Michalak Austen L.,
Trieger Greg W.,
Trieger Kelsey A.,
Godula Kamil
Publication year - 2022
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202101232
Subject(s) - microbiology and biotechnology , extracellular matrix , stem cell , glycan , growth factor , signal transduction , chemistry , fibroblast growth factor , regenerative medicine , cell signaling , biology , biochemistry , glycoprotein , receptor
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 (GFs) 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, a stem cell array platform is described, in which chemically modified heparan sulfate (HS) GAG polysaccharides are conjugated to a gelatin matrix and introduced into a polyacrylamide hydrogel network. This array allowed for direct analysis of HS contributions to the signaling via the FGF2‐dependent mitogen activated protein kinase (MAPK) pathway in mouse embryonic stem 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.