(Nanowerk Spotlight) Implantable bioelectronic devices have immense potential for monitoring and treating a wide range of medical conditions by interfacing directly with biological tissues and organs. However, conventional rigid electronics often have a significant mechanical mismatch with soft, wet tissues, leading to poor signal quality, tissue damage, and device failure. Researchers have long sought to develop soft, flexible bioelectronics that can conform to the contours of the body and seamlessly integrate with living systems.
In recent years, hydrogels have emerged as promising materials for implantable bioelectronics due to their tissue-like mechanical properties, high water content, and biocompatibility.
Conducting polymers, such as poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), have been incorporated into hydrogels to impart electrical conductivity while maintaining the hydrogels’ desirable properties.
However, fabricating complex 3D structures from conducting polymer hydrogels has remained challenging due to the intrinsic poor processability of conducting polymers and the difficulty in creating robust interfaces between the hydrogel components and biological tissues.
Now, a team of researchers in China has made a significant advance in this field by developing 3D printable conducting polymer hydrogels with superior printability, mechanical properties, and bioadhesion. In a paper published in the journal Advanced Functional Materials (“3D Printed Implantable Hydrogel Bioelectronics for Electrophysiological Monitoring and Electrical Modulation”), the scientists describe their innovative approach to formulating ink compositions for direct ink writing (DIW), a type of extrusion-based 3D printing.
3D printed hydrogel electronics for biointerfacing. a) Schematic illustration of hydrogel bioelectronics through the extrusion-based multimaterial direct ink writing (DIW) 3D printing technology. Three different inks were formulated for the printing of substrate layer, electrode layer and encapsulation layer. b) Schematic illustration of a three-dimensional printed (3DP) hydrogel bioelectronic device seamlessly adhered onto the biological tissue within a physiological environment for long-term bioelectronic interfacing (top), and also a magnified view of the mechanically compliant interface (bottom). The robust hydrogel-tissue interface is constructed through the synergy of chemical anchorage of polymer chains and energy dissipation within the hydrogel substrates, thus enabling the electrical recording and stimulation between hydrogel bioelectronics and biological tissues. (Reprinted with permission by Wiley-VCH Verlag) (click on image to enlarge)
By carefully tailoring the chemical components, such as polyvinyl alcohol (PVA), chitosan (CTS), and a synthetic copolymer of poly(acrylic acid-co-acrylic acid N-hydroxysuccinimide ester (PAA-NHS), the researchers created inks for the substrate, electrode, and encapsulation layers of the hydrogel bioelectronics.
The key to the success of this work lies in the synergistic combination of physical and chemical cross-linking mechanisms within the hydrogel network. The incorporation of PEDOT:PSS not only imparts conductivity but also functions as a rheological modifier. A rheological modifier is a substance that helps control the flow properties of the ink, enabling it to flow smoothly during extrusion and rapidly recover its solid-like behavior after printing. This allows for the fabrication of complex 3D structures with high fidelity. Post-printing chemical cross-linking further enhances the mechanical robustness and long-term stability of the hydrogel bioelectronics.
One of the most remarkable aspects of this work is the hydrogel bioelectronics’ ability to form instant and tough adhesion to various biological tissues, including skin, heart, blood vessels, and nerves. The researchers achieved this through a dry cross-linking mechanism involving the formation of covalent bonds, hydrogen bonds, and electrostatic interactions between the hydrogel and tissue surfaces.
This robust bioadhesion is crucial for maintaining a seamless and stable interface during the dynamic deformation of living tissues, such as the beating of a heart.
The team demonstrated the potential of their 3D printed hydrogel bioelectronics through a series of electrophysiological studies on rat heart models. The bioelectronics exhibited excellent mechanical compliance, conforming to the surface of the beating heart without interfering with its natural rhythm. The devices enabled high-precision spatiotemporal mapping of epicardial electrophysiological signals, successfully detecting abnormalities associated with cardiac arrhythmia and myocardial infarction.
Furthermore, the hydrogel bioelectronics could deliver electrical stimulation to restore normal heart rhythm, showcasing their potential for therapeutic applications.
The implications of this work extend far beyond cardiac monitoring and modulation. The ability to 3D print conducting polymer hydrogels with tailored mechanical, electrical, and adhesive properties opens up exciting possibilities for a wide range of implantable bioelectronic devices. These could include neural interfaces for brain-machine communication, gastric stimulators for treating digestive disorders, and bladder sensors for managing incontinence, among others.
The tissue-like nature of the hydrogel bioelectronics could greatly improve the long-term performance and biocompatibility of such devices, reducing the risk of inflammation, scarring, and rejection.
While the progress in this field is promising, several challenges need to be addressed before this technology can be fully realized. Long-term biocompatibility is crucial, as the materials must not provoke adverse immune responses over extended periods. Scalability of the manufacturing process is another significant challenge, as producing these devices on a commercial scale requires consistency and efficiency.
Finally, regulatory hurdles must be overcome to ensure that these new devices meet stringent safety and efficacy standards set by health authorities. These challenges highlight the need for ongoing research and development to transition these innovations from the lab to clinical practice.
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