Open research questions in Neuroscience and Neural Engineering
193 gap statements mined from Neuroscience and Neural Engineering papers in our 7.9M-paper local library, which holds 1,347 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
Current commercial nerve guidance conduits lack internal microarchitecture capable of guiding multiple fascicular pathways. Conventional neurophysiological systems are expensive, non-portable, and require specialized personnel.
Design-Stage Feasibility Study of an Integrated 3D-Printed Nerve Conduit and Portable Monitoring System · 2026 · DOINeed for multidisciplinary innovation to revolutionize healthcare and human-machine interaction.
The lack of knowledge on the biocompatibility of polymer materials for neural implants. The need to identify materials that can minimize foreign body reaction and ensure long-term biocompatibility. The gap in understanding the toxicity of polymer materials for neural implants.
Foreign Body Reaction to Neural Implants: A Comparative Study of Polymer Toxicity and Tissue Response · 2025 · DOITraditional electrodes have inadequate mechanical adaptability and reusability. There is a need for electrodes that can provide stable, long-duration recordings. Existing electrodes may not be suitable for continuous ophthalmic diagnostics and advanced wearable eye care applications.
There is a need for advanced neural interfaces that meet the requirements for precision, functionality, and safety. Current neural interfaces have limitations in terms of sensitivity, heat management, and biocompatibility.
Restoring motor and sensory function after spinal cord injury (SCI) through intraspinal microstimulation (ISMS) has primarily focused on gray matter targets, while the longitudinally organized axon tracts of spinal cord white matter remain an underexplored route for activating ascending sensory and descending motor pathways.
Nanopatterned Black Silicon Electrodes for High-Charge-Density Intraspinal Microstimulation · 2026 · DOISpatial cognition plays a critical role in survival and development, yet effective technologies for enhancing this capability remain scarce.
Modulation of place cells using targeted stimulation with bidirectional microelectrode arrays enhances spatial learning speed in mice · 2026 · DOIFurther researches are warranted to optimize CNTF properties, elucidate the underlying mechanisms of median nerve stimulation, and explore its potential in clinical applications.
Chronic CNT Fiber Interface With Median Nerve at Acupoint PC6 for Rat’s Myocardial Ischemia Control · 2025 · DOIGiven the multi-faceted parameter space of stimulation, it remains unclear how specific parameters (and their interactions) affect the spiking output of retinal ganglion cells (RGCs), particularly for direct versus network-mediated activation.
The Effects and Interactions of Epiretinal Electrical Stimulation Parameters on Direct and Network-Mediated Activation of Retinal Ganglion Cells · 2025 · DOIFollowing vision restoration, it is not yet known whether these visual regions are reinvigorated and regain a normal cortical thickness or retain the diminished thickness from blindness.
However, the neural origin of the different response components to ICMS are poorly understood, and the interactions between the three response components during trains of ICMS pulses remains unclear.
Neural mechanisms of the temporal response of cortical neurons to intracortical microstimulation · 2024 · DOINon-invasive or minutely invasive and wireless brain stimulation that can target any region of the brain is an open problem in engineering and neuroscience with serious implications for the treatment of numerous neurological diseases.
Intraneural stimulation of the auditory nerve is a promising alternative, but preclinical investigations of multi-electrode devices have been limited to acute or semi-chronic studies.
Future simulations will incorporate more realistic boundary conditions, anisotropic material behavior, and soft tissue contact models, - Future iterations will consider the integration of neurotrophic factors, - The development of preclinical prototypes is a potential future…
Design-Stage Feasibility Study of an Integrated 3D-Printed Nerve Conduit and Portable Monitoring System · 2026 · DOIStrategies to integrate neurotransmitter detection at multiple time scales, - Enable simultaneous detection of multiple analytes, - Employ methods to minimize sensor fouling and brain damage for long-term…
Recent Progress in Flexible Microelectrode Arrays for Combined Electrophysiological and Electrochemical Sensing · 2025 · DOIDevelopment of implantable electronic devices incorporating pressure or pH sensors into biliary stents, - Future development of brain-machine interfaces, - Exploration of the potential for application in the gastrointestinal…
Technological Advances and Medical Applications of Implantable Electronic Devices: From the Heart, Brain, and Skin to Gastrointestinal Organs · 2025 · DOIThe study does not provide a direct comparison with other methods, - The sample size is not explicitly stated, - The study is limited to cerebral organoids derived from human induced pluripotent stem…
Non-Invasive and Long-Term Electrophysiological Monitoring Sensors for Cerebral Organoids Differentiation · 2025 · DOIInvestigating the long-term stability of the MEA, - Exploring the application of the platform for other types of neural cells, - Developing a more efficient method for sterilizing…
Non-Invasive and Long-Term Electrophysiological Monitoring Sensors for Cerebral Organoids Differentiation · 2025 · DOIThe assumption that the voltammograms of the mixtures of DA and SE with constant DA and constant SE were the same may not be accurate, - The study used a limited number of discrete concentrations for DA and SE, - The study did not explore the effects of other factors that may affect the detection and prediction…
Pattern Recognition of Neurotransmitters: Complexity Reduction for Serotonin and Dopamine · 2025 · DOIExploring the effects of other factors that may affect the detection and prediction of NTs, - Investigating the use of other feature reduction methods, - Applying the methods to in vivo…
Pattern Recognition of Neurotransmitters: Complexity Reduction for Serotonin and Dopamine · 2025 · DOIDeveloping intelligent, responsive, and biointegrated systems, - Improving material stability, biocompatibility, and packaging durability, - Investigating regulatory approval, manufacturing scalability, and standardization of interfaces and data…
Emerging Implantable Sensor Technologies at the Intersection of Engineering and Brain Science · 2025 · DOIChronic immune responses and signal degradation. Mechanical fatigue from long-term implantation. Limitations in material stability, biocompatibility, and packaging durability.
Emerging Implantable Sensor Technologies at the Intersection of Engineering and Brain Science · 2025 · DOIFuture applications in brain-computer interfaces, - Development of more compact and power-efficient microsystems, - Investigation of the microsystem's potential for neuroscience…
Distinct Neural Activities in Hippocampal Subregions Revealed Using a High-Performance Wireless Microsystem with PtNPs/PEDOT:PSS-Enhanced Microelectrode Arrays · 2025 · DOIDeveloping a neuroelectronic interface that promotes neuron growth and development. Overcoming the neuroanatomical gap between electrodes and spiral ganglion neurons. Achieving precise stimulation and recording of neurophysiological activity.
A Neuroelectronic Interface with Microstructured Substrates for Spiral Ganglion Neurons Cultured In Vitro: Proof of Concept · 2025 · DOILimited number of experimental platforms for in vitro SGN growth and development, - The outcomes of implantation are still highly variable and often unpredictable, - The neuroanatomical gap (NAG) can severely reduce the electrical coupling (EC)…
A Neuroelectronic Interface with Microstructured Substrates for Spiral Ganglion Neurons Cultured In Vitro: Proof of Concept · 2025 · DOI
Most-cited papers in Neuroscience and Neural Engineering
- Neuronal ensemble control of prosthetic devices by a human with tetraplegia · Nature · 2006 · 2,795 citations
- Electrical bioadhesive interface for bioelectronics · Nature Materials · 2020 · 709 citations
- Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo · Nature Biotechnology · 2015 · 665 citations
- Topological supramolecular network enabled high-conductivity, stretchable organic bioelectronics · Science · 2022 · 608 citations
- A wireless millimetre-scale implantable neural stimulator with ultrasonically powered bidirectional communication · Nature Biomedical Engineering · 2020 · 453 citations
- Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics · Frontiers in Bioengineering and Biotechnology · 2021 · 441 citations
- Electroactive Biomaterials and Systems for Cell Fate Determination and Tissue Regeneration: Design and Applications · Advanced Materials · 2021 · 424 citations
- Wireless and battery-free technologies for neuroengineering · Nature Biomedical Engineering · 2021 · 347 citations
- Morphing electronics enable neuromodulation in growing tissue · Nature Biotechnology · 2020 · 319 citations
- Wearable plasmonic-metasurface sensor for noninvasive and universal molecular fingerprint detection on biointerfaces · Science Advances · 2021 · 315 citations
Most recent work
- Toward continuous monitoring systems: emerging trends of on-chip sensors in organ-on-a-chip · Microsystems & Nanoengineering · 2026
- Goal-directed learning in cortical organoids · Cell Reports · 2026
- Hydrogel-integrated multimodal physiological and modulation systems · Materials Horizons · 2026
- Skin Conformal Hydrogel Bioelectrodes for High‐Fidelity Electrophysiology and Human–Machine Interfaces · Advanced Healthcare Materials · 2026
- Shape-conformal porous frameworks for full coverage of neural organoids and high-resolution electrophysiology · Nature Biomedical Engineering · 2026
- Neural mechanisms underlying intracortical microstimulation for sensory restoration · Nature Biomedical Engineering · 2026
- Advanced liquid metal interfaces: engineering embodied cognition in closed-loop human-machine ecosystems · 中国科学通报：英文版 · 2026
- Flexible kirigami microelectrode arrays for neuronal activity recordings in non-human primate brains · Nature Electronics · 2026
- Inkube: an all-in-one solution for neuron culturing, electrophysiology, and fluidic exchange · Lab on a Chip · 2026
- Systematic evaluation of surgical insertion of flexible neural probe arrays into deeper brain targets using length modulation methods · Journal of Neural Engineering · 2026
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