Facile Fabrication of Injectable Alginate and Poly(3,4‐ethylenedioxythiophene)‐Based Soft Electrodes toward the Goal of Neuro‐Regenerative Applications

Abstract

Resident brain neural precursor cells (NPCs) are electrosensitive cells that respond to electric field application by proliferating, differentiating, and undergoing rapid and directed cathodal migration. Harnessing NPC potential is a promising strategy to facilitate neural repair following injury or disease. The use of electric fields to activate NPCs is limited by current electrode designs which are typically made of conductive metals that are stiff and can lead to neuroinflammation following implantation, in part due to the mechanical mismatch between physiological conditions and material. Herein, the design of a novel, injectable biobased soft electrode with properties suitable for electrical stimulation in vivo is explored. The recent interest in using biologically derived polymers which are relatively abundant and afford economic feasibility have been built upon. Sodium alginate is utilized to form soft hydrogels, thereby addressing the issue of mechanical mismatch, and the conductive polymer, poly(3,4‐ethylenedioxythiophene) (PEDOT), to generate an innovative new material. It is demonstrated that the optimized alginate PEDOT blend matches the modulus of the brain and is suitable for injection and is not cytotoxic to neural cells. Furthermore, in vivo studies demonstrate minimal activation of inflammatory cells upon implantation in the brain compared to classically used platinum‐based electrodes.

3D Printable Hydrogel Bioelectronic Interfaces for Healthcare Monitoring and Disease Diagnosis: Materials, Design Strategies, and Applications

“…In this context, recent studies indicate the use of naturallyderived conductive biopolymers, such as 𝛾-polyglutamic acid (𝛾-PGA) in combination with PEDOT:PSS improves the biocompatibility, adhesiveness, conductivity (∼12.5 S m −1 ), self-healing (healing time 2 s), stretchability (up to ≈300%) and flexibility (>300 kPa stress, ≈650% strain) towards wearable bioelectronics fabrication. [158] Similarly, many recent studies demonstrated that the use of chitosan, [159] alginate, [160][161][162][163] gelatin, [164][165][166][167][168] and cellulose [169][170][171][172][173] with PEDOT:PSS improved the conductivity and biocompatibility of the composites.…”

Injectable hydrogels in central nervous system: Unique and novel platforms for promoting extracellular matrix remodeling and tissue engineering

“…Current electrode designs, which are typically made of stiff conductive metals that can cause neuroinflammation after implantation in part due to the mechanical mismatch between implanted materials and physiological conditions, limit the use of electric fields to activate NPCs. In a study, alginate/PEDOT, a novel injectable biobased soft electrode with appropriate electrical stimulation characteristics, indicated a suitable blend matches with the brain tissue and negligible activation of inflammatory cells compared to traditionally used platinum-based electrodes [ 191 ].…”

Conducting Polymer Nanoparticles with Intrinsic Aqueous Dispersibility for Conductive Hydrogels

“…The kinetic stability of ncrys-PEDOT X was investigated by monitoring the absorbance of 1 wt% (10 mg mL −1 ) ncrys-PEDOT X aqueous dispersions over time (see the Experimental Section)-a common method to profile the sedimentation kinetics of nanomaterial dispersions. [36,37] Both ncrys-PEDOT 5 and ncrys-PEDOT 20 were first dispersed via stirring in either DI H 2 O or 2% aqueous sodium alginate, the latter of which is a common precursor for conductive biomaterials (Figure S2, Supporting Information); [38,39,40] such high filler concentrations are similar to those used with graphene oxide, and are orders of magnitude more concentrated than what can be achieved with untreated CNTs or G. For example, graphene nanoplatelets can only be dispersed in water without oxidation or complex surfactant optimization at concentrations less than 0.01 mg mL −1 . [41] In both DI and aqueous sodium alginate solutions the sedimen-tation of ncrys-PEDOT 5 and ncrys-PEDOT 20 were similar, however ncrys-PEDOT 5 had a relatively slower rate, potentially due to the elevated amount of PSS internal surfactant.…”