Tunable Conductive Hydrogel Scaffolds for Neural Cell Differentiation

Abstract

Multielectrode arrays would benefit from intimate engagement with neural cells, but typical arrays do not present a physical environment that mimics that of neural tissues. It is hypothesized that a porous, conductive hydrogel scaffold with appropriate mechanical and conductive properties could support neural cells in 3D, while tunable electrical and mechanical properties could modulate the growth and differentiation of the cellular networks. By incorporating carbon nanomaterials into an alginate hydrogel matrix, and then freeze‐drying the formulations, scaffolds which mimic neural tissue properties are formed. Neural progenitor cells (NPCs) incorporated in the scaffolds form neurite networks which span the material in 3D and differentiate into astrocytes and myelinating oligodendrocytes. Viscoelastic and more conductive scaffolds produce more dense neurite networks, with an increased percentage of astrocytes and higher myelination. Application of exogenous electrical stimulation to the scaffolds increases the percentage of astrocytes and the supporting cells localize differently with the surrounding neurons. The tunable biomaterial scaffolds can support neural cocultures for over 12 weeks, and enable a physiologically mimicking in vitro platform to study the formation of neuronal networks. As these materials have sufficient electrical properties to be used as electrodes in implantable arrays, they may allow for the creation of biohybrid neural interfaces and living electrodes.

Tunable hydrogel viscoelasticity modulates human neural maturation

“…Furthermore, harvested materials such as Matrigel suffer from large batch-to-batch variability (69). More recently, synthetic materials, including polyethylene glycol (PEG), polyacrylamide, and peptide amphiphile hydrogels, as well as semi-synthetic materials like alginate, have been used because they are well-defined and highly tunable systems, enabling carefully defined interrogation into how specific matrix properties influence cell fate (16,21,(70)(71)(72)(73)(74)(75). Previous work using viscoelastic alginate hydrogels revealed that hNPCs exhibit greater transcriptional differences in response to changes in stress relaxation rate compared to changes in hydrogel stiffness and cell-adhesive ligand concentration; however, the range of stiffness profiled was significantly higher than the stiffness of our HELP hydrogels used in the present manuscript, and no nonstress-relaxing alginate was included as a potential control (16).…”

Emerging biotransduction strategies on soft interfaces for biosensing

“…wave, wrinkle, island-bridge, origami, textile, and crack), which allows for conformability, high electron/hole mobility, low impedance/resistance, high throughput, and satisfactory sensing performance. [24][25][26][27][28] For biomolecule detection, as biomolecules could not directly produce detectable signals, biosensors generally need an extra biotransducer to selectively recognize molecules and subsequently produce electrical or optical signals. Hence, it is necessary to summarize efficient biotransduction strategies for better soft biosensors.…”

Energy‐Dissipative Hydrogels: A Promising Material for Tissue Regeneration†

“…In particular, it is viscoelasticity that is able to better mimic mechanical features of natural ECM, allowing larger neurite network construction. [ 119 ] Moreover, to induce the neuronal differentiation of BMSCs, Chen and colleagues fabricated AHA‐MA/Col hybrid hydrogel microfibers composed of collagens and aldehyde‐methacrylate dual‐ functionalized HA, which possessed orthogonal nano‐alignment and viscoelasticity owing to Schiff base formation of reversible imine crosslinks and microfluidic technique. They revealed the co‐effects of nano‐alignment and viscoelasticity on neurogenesis and demonstrated that such cooperation not only improved PC12 cells morphogenesis but also allowed neuronal differentiation of BMSCs, including up‐regulation of neurogenic genes expression, such as MAP‐2, nestin, NF‐L, NF‐M, and NSE, and neuronal specific protein Tuj‐1.…”