Advances in neural implant technology offer promising treatments for neurodegenerative diseases. Early efforts focused on electrode arrays for recording neural activity, enabling brain mapping and brain-machine interfaces. However, effective diagnosis and treatment require integrating monitoring and stimulation. Optogenetics, controlling neurons with light, offers high temporal accuracy and selective targeting, minimizing signal interference during recording. This approach has driven efforts to address neurological diseases. Comprehensive understanding of neural interplay necessitates implantable interfaces with high spatial and temporal resolution. Micro-neural implant electronics (µ-NIE) based on microelectromechanical systems (MEMS) are widely used, but inorganic materials cause mechanical mismatches with brain tissue, leading to damage and inflammation. Improvements using nanomaterials, soft polymers, and flexible structures enhance biocompatibility and enable long-term implantation, but secondary surgeries are still needed for removal. Bioresorbable neural implants offer a solution by degrading into harmless byproducts, eliminating the need for removal surgeries. While various transient neural electronics exist for recording, monitoring, and stimulation, multifunctional bioresorbable implants remain challenging due to material integration difficulties and design complexity. This study addresses this challenge by introducing a fully bioresorbable, flexible hybrid opto-electronic system for simultaneous electrophysiological recording and optical stimulation.

The literature extensively covers advancements in neural implant technology, highlighting the transition from simple recording electrodes to more sophisticated systems integrating stimulation and monitoring capabilities. The benefits and challenges of using inorganic materials in neural implants are well-documented, particularly the issue of tissue damage and inflammation due to mechanical mismatch. The field has seen significant progress in improving biocompatibility through the use of nanomaterials, soft polymers, and flexible designs. However, the need for secondary surgeries to remove implants remains a significant clinical challenge. The emergence of bioresorbable implants represents a major step forward, offering the potential to eliminate this need. Despite the progress in developing bioresorbable devices for single functionalities, the integration of multiple functions, such as simultaneous recording and stimulation, remains a significant hurdle. The existing literature lacks comprehensive examples of fully bioresorbable hybrid systems capable of achieving both optogenetic stimulation and high-fidelity electrophysiological recording, which necessitates innovative material selection and device design.

The study details the design and fabrication of a fully bioresorbable flexible neural implant. The device integrates a biodegradable poly(lactic-co-glycolic acid) (PLGA) waveguide for optical stimulation and a biodegradable Mo/Si bilayer electrode array for electrophysiological recording. The PLGA waveguide, optimized for total internal reflection (TIR), minimizes light transmission losses. The Mo/Si bilayer structure minimizes photoelectric artifacts from light absorption by the silicon layer during stimulation. Fabrication involved several steps: PLGA waveguide fabrication using soft lithography; Mo/Si electrode array fabrication through solid-state phosphorus doping, wet etching, and transfer printing; and device integration by bonding the electrode array to the PLGA waveguide and attaching ACF cables and fiber optic cannula. Device characterization included light transmission optimization through waveguide tip angle and electrode grid design adjustments, electrochemical impedance spectroscopy (EIS) to assess electrical properties, and accelerated degradation tests to determine bioresorption rate. In vitro photo-induced artifact evaluation was performed using a brain-mimicking hydrogel, while in vivo evaluations were conducted in wild-type and Thy-1:Channelrhodopsin-2 (ChR2) transgenic mice. In vivo experiments involved ECoG recording and optogenetic stimulation, with data analysis using MATLAB. Cell viability and immunohistochemistry analysis assessed biocompatibility.

The fabricated bioresorbable hybrid device successfully combined optogenetic stimulation and electrophysiological recording. The waveguide design, with a 50° tilted tip, maximized light transmission to the target tissue while minimizing reflections. The Mo/Si bilayer electrodes effectively eliminated photo-induced artifacts observed in monolayer Si electrodes, both in vitro and in vivo. In vivo experiments in Thy-1:ChR2 transgenic mice demonstrated reliable recording of spontaneous and induced seizure-like activity, as well as evoked LFPs during optogenetic stimulation for over two weeks. The device maintained stable performance for approximately three weeks before biodegradation began to affect functionality. Complete biodegradation occurred within eight weeks. In vitro cell viability tests showed high cell survival rates on the biodegradable electrodes, confirming excellent biocompatibility. Immunohistochemistry analysis revealed no significant difference in immune responses between the implantation site and the contralateral hemisphere, further supporting the biocompatibility of the device. The device’s functionality was verified by recording both spontaneous and pilocarpine-induced seizure-like activities, demonstrating its capacity to capture both physiological and pathological neural signals. Optogenetic stimulation yielded strong evoked LFPs with minimal artifacts.

This study successfully demonstrated a fully bioresorbable hybrid opto-electronic neural implant capable of simultaneous electrophysiological recording and optogenetic stimulation. The optimized waveguide and electrode design achieved efficient light transmission and artifact reduction, addressing a critical challenge in integrating optogenetics with neural recording. The excellent biocompatibility and successful chronic in vivo experiments validated the device's suitability for long-term implantation. The results address the need for transient neural implants that eliminate the risks and complications associated with secondary surgeries for device removal. This technology holds significant promise for neuroscience research and the treatment of neurological disorders requiring precise, targeted stimulation and real-time monitoring. The ability to record both physiological and pathological neural signals makes this device valuable for studying brain function and disease mechanisms.

This study presents a significant advancement in bioresorbable neural implants by creating a fully bioresorbable hybrid opto-electronic system capable of simultaneous electrophysiological recording and optogenetic stimulation. The device's superior biocompatibility, efficient light delivery, artifact minimization, and successful in vivo performance demonstrate its potential for both fundamental neuroscience research and clinical applications in treating neurological disorders. Future research should focus on increasing channel density, improving the control over biodegradation kinetics, and integrating wireless capabilities for more practical clinical translation.

While the study demonstrated the successful integration of optogenetic stimulation and electrophysiological recording in a bioresorbable device, there are several limitations. The current design uses a wired connection, limiting the freedom of movement for the animal. Future work will need to address this by integrating wireless communication capabilities. The study also used a relatively small number of electrodes. Increasing the electrode density is crucial for studying more complex neural circuits and obtaining higher spatial resolution. Further research should aim to optimize the biodegradation rate to extend the functional lifetime of the implant while ensuring timely bioresorption.