As life sciences and electrical engineering converge, bioelectronics has increasingly emerged as a pivotal force driving innovation in medicine, research, and industry. In particular, in the fields of tissue engineering and organ-on-a-chip technologies, developing efficient, versatile, and customizable electrode interfaces has become one of the central research priorities.

Although traditional microelectronic manufacturing technologies are well established, they still face numerous limitations when fabricating electrode systems with complex geometries, multilayer architectures, and flexible, reconfigurable designs. To address these challenges, the research community continues to explore novel fabrication approaches, integrating 3D bioprinting with micro‑ and nanofabrication techniques to pioneer bio‑inspired electronic interfaces.

Background

The advancement of tissue engineering hinges on high-performance bioelectronic interfaces. As a core platform for recording and stimulating electrical signals in neural and cardiac tissues, multi-electrode arrays (MEAs) are increasingly demanded to be highly flexible, ultrathin, customizable, and highly precise.

However, conventional microfabrication techniques such as photolithography and chemical etching suffer from drawbacks including high equipment costs, cumbersome processes, limited flexibility, and difficulty in meeting the demands of complex three-dimensional structures. These limitations constrain their application in in vivo settings or in the simulation of intricate tissue architectures.

Accordingly, researchers have proposed employing aerosol jet printing (AJP) technology, in conjunction with 3D bioprinting, to revolutionize the fabrication of microelectrode arrays (MEAs), enabling rapid, convenient, and personalized customization while supporting a wide range of materials and intricate architectures.

Advantages and Breakthroughs of AJP Technology

01 High Flexibility and High Resolution: Aerosol Jet Printing (AJP) enables the precise deposition of micron-scale patterns on non‑planar, flexible substrates, supporting the fabrication of complex 3D structures and surpassing the limitations of conventional planar microfabrication.

02 Material Diversity: Supports metals (such as gold and silver), conductive polymers, nanomaterials, and more, meeting diverse performance requirements including high electrical conductivity and excellent biocompatibility.

03 Fast and low-cost: No expensive micro‑lithography equipment or cleanroom conditions are required; the process is simple to operate, shortening the manufacturing cycle and reducing costs.

04 Scalability and Customizability: Enables personalized design, allowing rapid adjustments to array layout or shape to meet specific research or clinical requirements.

Design and Manufacturing Process

The research team first used computer-aided design (CAD) software to create multi-electrode arrays—available in various shapes such as circular or curved—that meet the requirements of tissue engineering. They then converted the design files into jetting paths and employed an aerosol‑based deposition system to precisely deposit metallic inks onto flexible thin films or 3D‑printed scaffolds.

In terms of fabrication, a multi‑layer jetting strategy is employed: conductive traces are printed first, followed by the deposition of electrodes and interconnects, and finally electrochemical modification is carried out to enhance electrical conductivity and stimulation performance.

Meanwhile, to ensure the biocompatibility and stability of the electrode materials, polymer coating and electrode electroplating were also employed. The entire process enables rapid mold fabrication in a dust-free environment, supporting both large-scale and personalized production.

I. Experimental Validation: Multifunctional, Multi-Material, and Multi-Structured MEAs

The research team conducted multiple experiments to evaluate the performance of AJP‑fabricated MEAs in biomedical applications:

• Electrical performance testing: Evaluated using metrics such as electrical conductivity and impedance, the results show that metal electrodes fabricated via AJP exhibit excellent conductivity and low noise, effectively meeting the requirements for recording neural and cardiac signals.

• Biocompatibility: Electrodes are coated with collagen (GelMA), and muscle cells and neurons are cultured on them. The cells exhibit robust growth, maintain a high viability, and show no significant cytotoxicity.

• Functional validation: Electrical stimulation was used to promote the directed growth of muscle cells, influencing their structure and function. In addition, electrical signals from both neurons and cardiomyocytes were successfully recorded, confirming the electrodes’ recording capability.

• Applications in Complex Structures: On 3D-printed tissue models, by integrating flexible materials with an AJP‑fabricated multi‑electrode system, electronic interfaces can be established for curved and bent structures, making this approach highly suitable for future organ‑on‑a‑chip platforms or organ‑simulating devices.

II. Key Technology: Flexible and Diversified Electrode Design

The research team has developed a diverse array of electrode architectures, including curled, bent, grid‑like, and lattice structures, to meet the needs of various tissue morphologies. Notably, in 3D‑bioprinted catheters or scaffolds, AJP electrodes can be seamlessly integrated, establishing a tightly coupled bioelectronic interface.

Furthermore, electrochemical deposition is employed to modify the electrode surface, enhancing its electrostimulatory performance, extending its operational lifespan, and ensuring long-term stability.

III. Practical Applications: From Cells to Tissues, from Basic Research to Clinical Translation

The core value of this technology lies in its broad application potential:

• Neuroscience research: Enables high-density, multi-site, multi-layer neural electrical signal recording and stimulation, providing technical support for brain–computer interfaces and neural network simulations.

• Cardiovascular tissue engineering: Establishing tissue models of cardiac muscle, blood vessels, and other tissues to enable electrical stimulation that promotes cell–cell coupling and functional synchronization, thereby providing a platform for cardiac disease research and drug screening.

• Musculoskeletal system: Develop organ‑on‑a‑chip models, such as muscle and electrical stimulation catheters, to advance research in muscle regeneration and rehabilitation technologies.

• Disease modeling and drug screening: Efficient generation of personalized, complex tissue models facilitates research into disease mechanisms and the development of new therapeutics.

Image and Text Guide

Figure 1. A) Schematic diagram of the microelectrode array platform for electrochemical stimulation and sensing. B) Schematic illustration of the aerosol jet printing process and the fabrication steps of the proposed MEA. C) Exploded view showing the components of the MEA. D) Proof-of-concept demonstrations of various applications using AJP‑printed MEAs, including planar in vitro MEA experiments, flexible MEA designs for DLP‑printed tissue models, and electrostimulation and electrochemical sensing.

Figure 2. A) Schematic illustration of the design and dimensions of the microelectrode array (MEA) and its stimulation electrodes. B–D) Optical microscopy images showing the printing quality of the MEA and the stimulation electrodes. E–F) Scanning electron microscopy (SEM) images depicting the surface topography of the stimulation electrodes and the microelectrodes.

Figure 3. Electrochemical characterization of gold MEAs fabricated via AJP. A) Bode magnitude plots for the sensing electrode, the stimulating electrode, and the PEDOT/PSS‑coated stimulating electrode. B) Bode phase plots for the different electrodes (sensing electrode, n = 21; stimulating electrode, n = 18; PEDOT/PSS‑coated stimulating electrode, n = 4). C) Comparison of inter‑sample and intra‑sample relative standard deviations for pure gold electrodes: inter‑sample (sensing electrode on oneMEA, n = 25) and intra‑sample (sensing electrodes across four MEAs, n = 100). D, E) Comparison of impedance magnitudes at 1 kHz and 1 Hz (sensing electrode, n = 21; stimulating electrode, n = 18; PEDOT/PSS‑coated stimulating electrode, n = 4). F) Comparison of 1 kHz impedance magnitudes on day 0 and day 14 under standard cell‑culture conditions (n = 23). G) Percentage increase in 1 kHz electrode impedance before and after coating with GelMA, PDL, gelatin, and fibronectin (n = 4). H) Representative voltage traces of CICmax for a gold stimulating electrode versus a PEDOT/PSS‑coated stimulating electrode, with currents applied to the conventional gold and PEDOT/PSS electrodes of 575 and 2575 μA, respectively. I) Comparison of CICmax between the stimulating gold electrode and the PEDOT/PSS‑coated stimulating electrode (n = 4). J) Stability of the PEDOT/PSS‑coated stimulating electrode under 50 Hz biphasic pulses (n = 3). Error bars represent standard deviation. (ns, p > 0.05; *** p < 0.001; **** p < 0.0001).

Figure 4. Live/dead cell viability assay of bioprinted C2C12 cells with 10% encapsulation, evaluating the cellular compatibility of AJP‑printed gold MEAs in GelMA (w/v). A) Representative images captured using a 10× objective (scale bar, 100 μm). B) Bar graph showing the mean percentage of live cells; three samples were cultured for 7 days, with seven images acquired per sample. Error bars indicate standard deviation. (ns = not significant, p > 0.05).

Figure 5. Electrostimulation induces directional alignment of C2C12 cells. A) Representative fluorescence images of actin‑stained C2C12 cells on the MEA under electrostimulation. The stimulation direction is indicated by red double‑headed arrows; white dashed lines mark the electrode positions. B) Polar plot of the orientation‑angle distribution obtained from image analysis of the stimulated group (n = 3, 30 sample images). C) Representative fluorescence images of actin‑stained C2C12 cells on the MEA without stimulation. White dashed lines indicate the electrode positions. D) Polar plot of the orientation‑angle distribution obtained from image analysis of the control group (n = 3, 30 sample images).

Figure 6. Extracellular recordings from AJP‑printed MEAs. A) Filtered electrophysiological recordings from neurons in the primary motor cortex. B) Overlaid spike waveforms detected from neurons in the primary motor cortex. C) Representation of the AJP‑printedMEA on a DLP‑printed brain model. D) The mean waveform and standard deviation (shaded area) derived from (B). E) Filtered electrophysiological recordings from cultured HL‑1 atrial cardiomyocytes. F) Overlaid spike waveforms detected from HL‑1 cells. G) Representation of the AJP‑printedMEA on a DLP‑printed cardiac model. H) The mean waveform and standard deviation (shaded area) derived from (F).

Figure 7. Electrical stimulation of bio‑3D‑printed conduits. A) Control group and B) Electrically stimulated group: Fluorescent confocal images showing the growth of activated (green) C2C12 cells within the conduit pores (magnification ×2.5). Insets show a ×10 magnification view. Nuclei are counterstained with blue DAPI. Red arrows indicate the direction of electrical stimulation. Scale bar = 200 μm (n = 1). C) Digital photograph of a conformal MEA with printed hydrogel in the center. D) 3D rendering of the hydrogel within the conformal MEA electrode system. The figure illustrates the direction of cell proliferation (scale bar = 1 cm).

Aerosol jet printing (AJP), an innovative approach integrated with 3D bioprinting, offers a groundbreaking technological pathway for next‑generation tissue engineering and organ‑on‑a‑chip applications. By overcoming the limitations of conventional microfabrication, it enables high‑speed, flexible, customizable, and multifunctional electronic interfaces, laying a robust foundation for the research and clinical application of diverse tissues, including neural, cardiac, and muscular tissues.

In this paper, the research team successfully employed AJP technology to print a variety of key materials, including metallic conductive materials such as gold nanoparticles (AuNPs) and conductive polymers like PEDOT:PSS, thereby fabricating flexible, multifunctional multi-electrode arrays. They also used photosensitive insulating inks to print insulating layers, resulting in a complete multilayer electrode architecture (T3, T4, T6). Furthermore, the study printed biocompatible conductive materials that exhibited excellent cell compatibility and seamlessly integrated with 3D‑printed scaffolds and catheters for cell culture and electrical stimulation experiments, demonstrating the efficient coupling between electronic interfaces and biological tissues.

In the future, as technology continues to advance and cross-disciplinary integration deepens, 3D bio‑electronic manufacturing will emerge as a powerful driver of life‑science progress and a key enabler of improved human health. We look forward to seeing more intelligent medical devices based on AJP, ushering in transformative advances for personalized, precision medicine—such as customized neural interfaces, cardiac repair devices, and muscle‑regeneration scaffolds. Leveraging the material diversity and manufacturing flexibility of AJP, these innovative applications will open up vast new prospects for next‑generation, precise, and sustainable biomedical technologies.

Original article link: www.advhealthmat.de