3D printing for optogenetic devices in neuroengineering applications from precise in vitro control to efficient in vivo implant systems

Abstract Optogenetic devices have been widely used in neuroscience and related disciplines, providing precise neural circuit modulation with high spatiotemporal resolution. Notably, three-dimensional (3D) printing has emerged as a powerful tool for designing and fabricating optogenetic devices due to its unique capability for rapidly prototyping intricate and customized structures. In this review, we first outline and compare various 3D printing technologies, evaluating their strengths and limitations to guide the development of personalized optogenetic devices. Then, we discuss 3D-printed devices designed for in vitro research scenarios, demonstrating their potential for achieving high-throughput optogenetic platforms for cell signaling, optogenetic control of cellular functions, and tailored platforms for advanced neuromodulation. Furthermore, we detail key strategies for the development of 3D-printed devices for in vivo applications, including the construction of light-delivery systems in terms of precise device fabrication, improved optical performance, and system-level integration. Furthermore, to provide a comprehensive evaluation of the advantages and limitations of different fabrication approaches, we conduct a multi-dimensional comparison of in vivo optogenetic devices prepared by traditional and 3D printing techniques. Finally, we highlight several key challenges and future directions in this rapidly advancing field, aiming to guide the continued development and application of 3D-printed optogenetic devices.