A newly developed conductive hydrogel mimics key features of living tissue and can also sense oxygen and use electrical signals to control the release of growth factors.
Study: Conductive Hydrogels for Exogenous Sensing and Cell Fate Control. Image Credit: Quality Stock Arts/Shutterstock.com
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Next-Gen Bioelectronic Materials
Flexible and stretchable electronics have brought medical devices into much closer mechanical alignment with soft tissue. But there is still a basic mismatch: most bioelectronic materials are chosen for how well they conduct electricity or fit into microfabrication workflows, not for how well they behave like biology.
This is important due to the chemical activity of native tissue. The extracellular matrix (ECM) helps regulate cell behavior by storing, presenting, and releasing signaling molecules, such as growth factors and cytokines.
Reproducing that kind of dynamic biochemical function is a major technical hurdle in bioelectronics.
Conductive hydrogels have helped answer this problem. Materials such as poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate), or PEDOT:PSS, combine softness and hydration with mixed ionic-electronic transport, making them useful in electrodes for sensing or pacing electroactive cells, as well as in small-molecule drug delivery.
Other conductive hydrogels incorporating decellularized tissues, glycosaminoglycans, or polysaccharides have also been explored, often to improve conductivity or cytocompatibility.
But truly tissue-mimetic bioelectronic materials remain elusive. In this study, published in Advanced Materials, the authors describe their work as an early step toward an electronic extracellular matrix. This electronic ECM is a material system in which electronic signals can influence biomolecular interactions, and biomolecular interactions may in turn affect electronic behavior.
Designing the Electronic Extracellular Matrix
The researchers built their material around sulfated glycosaminoglycan-containing hydrogels (sGAGh), which are already known to bind and release ECM-associated cytokines and growth factors. They then introduced the semiconducting polymer PEDOT into that soft hydrogel network, creating a material they call PEDOT:sGAGh.
The result was a hydrogel with dual ionic-electronic conductivity, designed to allow on-demand control of biomolecular interactions under biologically compatible electrochemical conditions.
To make the hydrogel templates, the team used two crosslinking approaches:
- Michael-type thiol-maleimide click chemistry, combining maleimide-conjugated heparin with four-arm thiol-terminated polyethylene glycol, or starPEG-SH, at a 1:1 molar ratio.
- EDC/NHS chemistry, mixing heparin with four-arm PEG-amine and replacing part of the heparin with PEG-carboxylic acid to tune the material’s anionic charge density.
In both systems, the aim was to vary the charge while preserving overall network structure.
PEDOT was then added by oxidative polymerization. The sGAGh templates were first incubated in ammonium persulfate dissolved in hydrochloric acid, then immersed in 3,4-ethylenedioxythiophene, or EDOT, dissolved in mineral oil.
Residual monomer and oil were removed with hexane, and the material was then washed and stored in phosphate-buffered saline.
The team went on to prepare electrode-integrated samples, characterize the material’s nanostructure and electrochemistry, examine its interactions with proteins, conduct cell-culture studies, build organic electrochemical transistors (OECTs), and develop a proof-of-concept biohybrid circuit.
PEDOT Hydrogel Success
The researchers showed that PEDOT could be polymerized in situ within the ECM-inspired hydrogel template, producing a material that was bioactive, electrochemically responsive, and dynamically addressable.
They found that hydrophobic substitutions in the hydrogel template likely encouraged the formation of PEDOT-rich clusters. In the highest-performing formulation, those clusters formed percolating conductive networks resembling three-dimensional filled polymer composites.
Unlike conventional composites, however, the material remained overwhelmingly water-rich, at about 95 wt.%. That high water content enabled proteins and other macromolecules to diffuse throughout the bulk of the hydrogel rather than interacting only at the surface.
The amount of PEDOT needed was also low. Less than 1 wt.% was enough to make the material electroactive while maintaining tissue-like softness, although the paper notes differences between local and bulk mechanical measurements after PEDOT incorporation.
The material also showed strong affinity for bioactive proteins, including growth factors. Under low-voltage stimulation, oxidizing potentials promoted retention, while reducing potentials enhanced release.
That behavior was then linked to cell responses in proof-of-concept models. In one set of experiments, electrically controlled VEGF handling influenced vasculogenic responses in human umbilical vein endothelial cells, or HUVECs. In another, nerve growth factor, or NGF, release promoted neurite outgrowth in PC12 cells.
The researchers also integrated PEDOT:sGAGh into bioactive electrode coatings and three-dimensional OECTs. In device experiments, the material functioned as an oxygen sensor. They then combined sensing and actuation in a proof-of-concept biohybrid circuit, linking low-oxygen detection to NGF release and downstream neurite outgrowth.
Study Significance
The study is significant for demonstrating the successful production of a soft, conductive material and for showing how a hydrogel can sit at the boundary between molecular biology and electronics.
The authors argue that PEDOT:sGAGh could serve as a versatile platform for biohybrid circuits that connect molecular signaling with solid-state electronics.
In principle, this may help future interfaces move toward more advanced systems that detect biochemical states and respond by delivering regenerative cues.
They are careful, however, not to present this as a finished therapeutic platform. The paper describes the work as an early step and points to several challenges ahead, including long-term maintenance of protein bioactivity, molecular specificity, matrix remodelability, and the addition of other ECM components.
For a field trying to make electronics behave more like living tissue, the work offers a clear and technically detailed advance.
Journal Reference
Akbar, T. F. et al. (2026). Conductive Hydrogels for Exogenous Sensing and Cell Fate Control. Advanced Materials, e72866. DOI: 10.1002/adma.72866
