A team led by researchers at Lancaster University has developed a method to 3D-print flexible electronics using a conducting polymer, and the team has demonstrated a method to directly print these electrical structures on or in living organisms. Although the process is at a proof-of-concept stage, the researchers believe that their additive manufacturing method, when fully developed, has the potential to print patient-specific implants for a variety of applications, including real-time health monitoring and medical interventions, such as treating epilepsy or pain. The researchers used the polymer polypyrrole in the work, as well as an erbium-doped fiber laser with a 780-nm wavelength and operating at a repetition rate of 100 MHz. They performed in silico toxicity screening of the ink components to identify and confirm cytocompatible formulations and created 3D objects with integrated electronics using a multiphoton fabrication process. They found that 3D printing with light-transmitting materials yielded well-resolved, conductive, micrometer-scale features. In the first part of the two-stage study, the researchers used a high-resolution laser printer (a nanoscribe) and an additive process to 3D-print an electrical circuit directly within a silicone matrix. They assessed the fidelity of the printing process using OCT and then demonstrated that the 3D-printed electronics could stimulate mouse neurons in vitro. “We took 3D-printed electrodes and placed them on a slice of mouse brain tissue that we kept alive in vitro. Using this approach, we could evoke neuronal responses that were similar to those seen in vivo,” said Damian Cummings, a researcher at University College London. In the second stage, the researchers 3D-printed conducting structures directly in C. elegans nematode worms, demonstrating that the entire process — ink formulations, laser exposure, and printing — was compatible with living organisms. The researchers selected C. elegans in part due to its high sensitivity to heat, desiccation, and physical injury, which makes the organism an ideal testing ground for biosafe laser-based in vivo printing approaches in biomedicine, the researchers said in their paper. “Achieving laser printing on/in live C. elegans would require the lowest possible laser power that enables ink polymerization and biocompatible ink components,” they said. Rather than using needles, researcher Alexandre Benedetto said, the researchers used smart ink and lasers to “tattoo” conductive patches onto the tiny worms. The results showed that the researchers could use the technology to achieve the resolution, safety, and comfort levels required for medical applications, he said. Although improvements in infrared laser technology and in smart ink formulation and delivery are critical to translating 3D-printing of medical electronics to the clinic, the method developed by the Lancaster team could help pave the way for biomedical innovations. According to John Hardy, a researcher on the work, technologies such as the one demonstrated by the team could be used to fix broken implanted electronics through a process such as laser dental or eye surgery. (Left) A researcher uses nanoscribe. The printing has to be undertaken in orange light. (Center) Examples of shapes printed using this technique. (Right) Material that was printed in worms included an embedded star shape from printed ink. Unpolymerized material, such as the ink, shines green under UV light. Courtesy of Lancaster University. Star and square images courtesy of Alexandre Benedetto. The technical advantages of electronics produced via this multiphoton fabrication technique could include more accurate targeting (i.e., fewer cells stimulated or recorded from) to minimize adverse effects such as tissue damage and immunological reactions. Further, they could create the potential for more simultaneous sites for stimulation or recording with optimized signal-to-noise ratios. Potential applications include improved electrodes for deep brain stimulation for the treatment of Parkinson’s disease and epilepsy; neuroprosthetics for traumatic brain injury; new ways to monitor and treat neuromuscular disorders; and new approaches to neuromodulation for pain. The experimental results also demonstrate the potential for using additive manufacturing approaches to produce integrated electronics for bespoke medical applications. The researchers are investigating different types of materials that could be used for 3D-printing electronics, and also looking into the types of structures that it is possible to print using the multiphoton fabrication process. They are also developing prototypes to show to potential end users who may be interested in co-developing the technology, which is estimated to be about 10 to 15 years away from full development. The research was published in Advanced Materials Technologies (www.doi.org/10.1002/admt.202201274).