Electroresponsive Hydrogels for Therapeutic Applications in the Brain

Abstract

Electroresponsive hydrogels possess a conducting material component and respond to electric stimulation through reversible absorption and expulsion of water. The high level of hydration, soft elastomeric compliance, biocompatibility, and enhanced electrochemical properties render these hydrogels suitable for implantation in the brain to enhance the transmission of neural electric signals and ion transport. This review provides an overview of critical electroresponsive hydrogel properties for augmenting electric stimulation in the brain. A background on electric stimulation in the brain through electroresponsive hydrogels is provided. Common conducting materials and general techniques to integrate them into hydrogels are briefly discussed. This review focuses on and summarizes advances in electric stimulation of electroconductive hydrogels for therapeutic applications in the brain, such as for controlling delivery of drugs, directing neural stem cell differentiation and neurogenesis, improving neural biosensor capabilities, and enhancing neural electrode-tissue interfaces. The key challenges in each of these applications are discussed and recommendations for future research are also provided.

Method Matters: Exploring Alkoxysulfonate-Functionalized Poly(3,4-ethylenedioxythiophene) and Its Unintentional Self-Aggregating Copolymer toward Injectable Bioelectronics

“…Injectable conductive hydrogels have shown great biocompatibility because of their resemblance to body tissue. Conductive hydrogels are in general composed of a hydrogel matrix (e.g., alginate, hyaluronic acid, or chitosan) supplemented by a conductive polymer (e.g., PEDOT:PSS, polypyrrole, or oligo-/polyaniline) and have conductivities in a low mS cm –1 range. , In the search for a material that allows for the installation of different functional groups to diversify functionality toward controlling solubility–aggregation properties and biocompatibility, the polymer poly­(3,4-ethylene-dioxythiophene) doped with poly­(styrene sulfonate) (PEDOT:PSS) − was of interest. PEDOT:PSS displays high conductivity and the possibility for structural manipulation of the EDOT monomer. − Recently, a mixture of PEDOT:PSS and 4-dodecylbenzenesulfonic acid (DBSA) was reported to form hydrogels at room temperature after 2–200 min, depending on the concentration of DBSA.…”

Development of a Synthetic, Injectable Hydrogel to Capture Residual Glioblastoma and Glioblastoma Stem‐Like Cells with CXCL12‐Mediated Chemotaxis

“…[98] Cured and equilibrated hydrogels possessed electroconductivities ranging from 0.255 to 0.329 S m −1 , which is within the range necessary for controlled delivery of therapeutic hydrogel payloads upon electric stimulation. [80] The hydrogels can potentially be used for electrotaxis, as conductivities around 1.5 S m −1 can model electrolyte solutions during computational simulations of GBM electrotaxis. [98,99] Our results indicated the GSC population is heterogeneous during the invasion.…”

“…[ 79 ] However, the limited number of these micrometer‐sized pores on the hydrogel surface may have contributed to the limited number of GBM/GSC invasions observed. Future research will study if physical stimuli, like focused ultrasound or electric fields, [ 80 ] can be applied to spatiotemporally control the delivery of CXCL12 retained in the hydrogel as well as the hydrogel pore sizes and porosity to improve cell entrapment.…”

Bioprinting for bone tissue engineering

“…Stimulus translation is achieved through water and action, elastic compliance, biocompatibility, and electrochemical efficacy. Electrically stimulated conductive hydrogels can control drug delivery and induce stem cell differentiation, vascular regeneration, and neurogenesis (Khan et al, 2022). In short, the electrical signal is applied in the microfluidic platform to use the conductive hydrogel as an effective actuator.…”