Alginate Sulfate Substrates Control Growth Factor Binding and Growth of Primary Neurons: Toward Engineered 3D Neural Networks

• DOI: 10.1002/adbi.202000047
• Publication Date: 2020-05-28T06:46:45Z
• Authors: Georges Kfoury; Vanessa El Habbaki; Waddah Malaeb; Sean Weaver; Dmitry Momotenko; Rami Mhanna
• Keywords: Neurons; Rats, Sprague-Dawley; 0301 basic medicine; 03 medical and health sciences; Alginates; 3D Cultures; Alginate sulfate; Growth factors; Neural networks; Primary neurons; Nerve Growth Factor; Primary Cell Culture; Animals; Fibroblast Growth Factor 2; Nerve Net; Rats

AbstractSulfated glycosaminoglycans (sGAGs) are vital molecules of the extracellular matrix (ECM) of the nervous system known to regulate proliferation, migration, and differentiation of neurons mainly through binding relevant growth factors. Alginate sulfate (AlgSulf) mimics sGAGs and binds growth factors such as basic fibroblast growth factor (FGF‐2). Here, thin films of biotinylated AlgSulf (b‐AlgSulfn) are engineered with sulfation degrees (DS = 0.0 and 2.7) and the effect of polysaccharide concentration on FGF‐2 and nerve growth factor (β‐NGF) binding and subsequent primary neural viability and neurite outgrowth is assessed. An increase in b‐AlgSulfnconcentration results in higher FGF‐2 and β‐NGF binding as demonstrated by greater frequency and dissipation shifts measured with quartz crystal microbalance with dissipation monitoring (QCM‐D). Primary neurons seeded on the 2D b‐AlgSulfnfilms maintain high viability comparable to positive controls grown on poly‐d‐lysine. Neurons grown in 3D AlgSulf hydrogels (DS = 0.8) exhibit a significantly higher viability, neurite numbers and mean branch length compared to neurons grown in nonsulfated controls. Finally, a first step is made toward constructing 3D neuronal networks by controllably patterning neurons encapsulated in AlgSulf into an alginate carrier. The substrates and neural networks developed in the current study can be used in basic and applied neural applications.