Tailoring 3D hydrogel systems for neuronal encapsulation in living electrodes

Abstract

State‐of‐the‐art neurorprostheses rely on stiff metallic electrodes to communicate with neural tissues. It was envisioned that a soft, organic electrode coating embedded with functional neural cells will enhance electrode‐tissue integration. To enable such a device, it is necessary to produce a cell scaffold with mechanical properties matched to native neural tissue. A degradable poly(vinyl alcohol) (PVA) hydrogel was tailored to have a range of compressive moduli through variation in macromer composition and initiator amount. A regression model was used to predict the amount of initiator required for hydrogel polymerization with nominal macromer content ranging between 5 and 20 wt %. Hydrogels at 5 and 10 wt % were reliably formed but 15 wt % and above were not able to be fabricated due to the light attenuation properties of the initiator ruthenium at increased concentration. Compressive modulus of hydrogels decreased upon incorporation of biomolecules (sericin and gelatin), however, the bulk stiffness spanned the range required to match neural tissue properties (0.04–20kPa). Neuroglia cells, such as Schwann cells survived and grew within the scaffold. The significant finding of this work is that the PVA‐tyramine system can be tuned to provide a soft degradable scaffold for neural tissue regeneration while presenting bioactive molecules for cellular expansion. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 273–287

Tissue engineered hydrogels supporting 3D neural networks

“…In particular, the PVA-Tyr system allows covalent crosslinking with unmodified sericin and gelatin (PVA-SG) to respectively protect cells from the initial polymerization process and present cells with initial attachment cues. Previous research by Aregueta-Robles et al [32] has shown that PVA-SG can be tailored into polymeric scaffold variants that present SCs with a compressive modulus (K) from 2 kPa to 16 kPa, which is comparable to literature reports of nerve tissue stiffness [6,33]. While it was demonstrated that SCs survived and remained viable following the initial polymerisation process, the cell growth and development into functional phenotypes was not examined.…”

“…Two variations of PVA-SG were fabricated via changes on macromer content as previously described [32]. In brief, gelatin (1 wt%) from porcine skin, (…”

Hydrogels for 3D Neural Tissue Models: Understanding Cell-Material Interactions at a Molecular Level

“…Hydrogels have been employed as 3D constructs which mimic the natural mechanical and structural properties of soft tissue (Khetan and Burdick, 2009;Goding et al, 2019;Syed et al, 2020). A biosynthetic PVA-SG hydrogel construct was chosen as the platform for this study, as it can be tailored to improve outcomes for neural cell encapsulation, as shown in prior research (Goding et al, 2017;Aregueta-Robles et al, 2018). The key objective of this study was to develop an understanding of neural cellular response to hydrogel encapsulation, to inform the design of future hydrogel constructs for neural tissue engineering applications, with the end goal of a hydrogel carrier which enables the development of complex neural networks such as those observed in vivo.…”

“…Hydrogel physical characterization was performed as described by Aregueta-Robles et al (2018). Immediately after photopolymerization, 3 samples per time point (0, 1, 3, 7, 10, 14, 21, 28 days) were weighed to determine their initial wet mass (m i ).…”

“…Uniaxial compression tests were performed using a Bose ElectroForce 3200 with a 2.5 N load cell at a crosshead speed of 0.5 mm/min as described by Aregueta-Robles et al (2018). Hydrogel thickness and diameter were recorded prior to testing and samples were kept in DPBS during the measurements.…”