Bioelectronic Medicine and Neural Interfaces: Smart Therapeutic Technologies for Biomedical Innovation

Background: Bioelectronic medicine is an emerging therapy that makes use of neural signals and the nervous system to help in the treatment of injuries and diseases. The nervous sys-tem consists of disciplined circuits that involve the communication of every major organ of the human body as all the organs of the human body are regulated and controlled by neural circuits. Objective: The objective of this review is to overview the current implementations of bioelectron-ic medicines within the human body. The main target is to heal the body without administering a wide array of exogenous drugs. On understanding these neural circuits at a molecular level, it could be possible to understand, manipulate, and modify the body’s functioning with the help of electrical impulses to modify neural impulses. Methods: The literature related to bioelectronic medicines, and their applications was collected through different websites, academic research portals, and databases, sorted, and presented in this review. Results: Bioelectronic medicine is emerging as a cutting-edge area in healthcare, demonstrating its potential to transform the diagnosis and management of inflammation and related conditions. With established efficacy in a variety of disorders and marketed available treatments, it highlights an enormous shift toward individualized and specialized therapeutic approaches, providing prom-ise for improved outcomes and a higher quality of life for patients worldwide. Conclusion: The study focuses on potential advances in bioelectronic medicine for alleviating in-flammation and inflammatory disorders such as rheumatoid arthritis, diabetes, and spinal cord in-jury. Bioelectronic treatments provide innovative therapeutic options with the potential for con-siderable clinical effects.

Neurological diseases can be treated in a whole new way with bioelectronic medicine, which uses neural connections to directly communicate with the nervous system. This field blends neuroscience, engineering, and clinical practice to make gadgets that can change nerve activity with a level of accuracy that has never been seen before. Recent progress in biomedical engineering has made it possible to create very complex neural connections that can record and trigger activity in neurones at the very small scale. For many neurological conditions, like Parkinson's disease, epilepsy, and chronic pain, these gadgets show promise as new ways to treat them. Traditionally, these conditions have been hard to control with medicine alone. Electrical activation of nerves to repair or change brain function is what bioelectronic medicine is all about. One example is vagus nerve stimulation (VNS), which has become a useful way to help people with refractory epilepsy and depression. This shows that neural interfaces can have big practical effects. Deep brain stimulation (DBS), which uses electrical signals to target specific parts of the brain, has also made a huge difference in the movement ability of people with Parkinson's disease. Adding bioelectronics to real-time data analytics and machine learning methods is also making it possible for treatments that can change based on the brain state of the patient? This personalized method not only makes treatments work better but also cuts down on side effects, which is a big change from the old way of doing things where one answer fits all. Biocompatibility of implanted devices, long-term security of neural interfaces, and ethical concerns about device placement and brain editing are some of the problems that this field is facing as it changes quickly. These problems are still being studied and tested in humans, with the goal of creating better, more successful, and less invasive solutions.

Biomaterials-based bioengineering strategies for bioelectronic medicine

Bioelectronic medicine is a multidisciplinary field that combines molecular medicine, neurology, engineering, and computer science to design devices for diagnosing and treating diseases. The advancements in bioelectronic medicine can improve the precision and personalization of illness treatment. Bioelectronic medicine can produce, suppress, and measure electrical activity in excitable tissue. Bioelectronic devices modify specific neural circuits using electrons rather than pharmaceuticals and uses of bioelectronic processes to regulate the biological processes underlining various diseases. This promotes the potential to address the underlying causes of illnesses, reduce adverse effects, and lower costs compared to conventional medication. The current review presents different important aspects of bioelectronic medicines with recent advancements. The area of bioelectronic medicine has a lot of potential for treating diseases, enabling non-invasive therapeutic intervention by regulating brain impulses. Bioelectronic medicine uses electricity to control biological processes, treat illnesses, or regain lost capability. These new classes of medicines are designed by the technological developments in the detection and regulation of electrical signaling methods in the nervous system. Peripheral nervous system regulates a wide range of processes in chronic diseases; it involves implanting small devices onto specific peripheral nerves, which read and regulate the brain signaling patterns to achieve therapeutic effects specific to the signal capacity of a particular organ. The potential for bioelectronic medicine field is vast, as it investigates for treatment of various diseases, including rheumatoid arthritis, diabetes, hypertension, paralysis, chronic illnesses, blindness, etc.

Plant-derived bioactive compounds and their novel role in central nervous system disorder treatment via ATF4 targeting: A systematic literature review

Rho-kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase Rho. The Rho-ROCK pathway is involved in many aspects of neuronal functions including neurite outgrowth and retraction. The Rho-ROCK pathway becomes an attractive target for the development of drugs for treating central nervous system (CNS) disorders, since it has been recently revealed that this pathway is closely related to the pathogenesis of several CNS disorders such as spinal cord injuries, stroke, and Alzheimer’s disease (AD). In the adult CNS, injured axons regenerate poorly due to the presence of myelin-associated axonal growth inhibitors such as myelin-associated glycoprotein (MAG), Nogo, oligodendrocyte-myelin glycoprotein (OMgp), and the recently identified repulsive guidance molecule (RGM). The effects of these inhibitors are reversed by blockade of the Rho-ROCK pathway in vitro, and the inhibition of this pathway promotes axonal regeneration and functional recovery in the injured CNS in vivo. In addition, the therapeutic effects of the Rho-ROCK inhibitors have been demonstrated in animal models of stroke. In this review, we summarize the involvement of the Rho-ROCK pathway in CNS disorders such as spinal cord injuries, stroke, and AD and also discuss the potential of Rho-ROCK inhibitors in the treatment of human CNS disorders.

Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation of the nervous system by precise delivery of electrical current for the treatment of clinical conditions, such as post-stroke movement recovery or drug-resistant disorders. The unquestionable clinical impact of Bioelectronic Medicine is underscored by the successful translation to humans in the last decades, and the long list of preclinical studies. Given the emergency of accelerating the progress in new neuromodulation treatments (i.e., drug-resistant hypertension, autoimmune and degenerative diseases), collaboration between multiple fields is imperative. This work intends to foster multidisciplinary work and bring together different fields to provide the fundamental basis underlying Bioelectronic Medicine. In this review we will go from the biophysics of the cell membrane, which we consider the inner core of neuromodulation, to patient care. We will discuss the recently discovered mechanism of neurotransmission switching and how it will impact neuromodulation design, and we will provide an update on neuronal and glial basis in health and disease. The advances in biomedical technology have facilitated the collection of large amounts of data, thereby introducing new challenges in data analysis. We will discuss the current approaches and challenges in high throughput data analysis, encompassing big data, networks, artificial intelligence, and internet of things. Emphasis will be placed on understanding the electrochemical properties of neural interfaces, along with the integration of biocompatible and reliable materials and compliance with biomedical regulations for translational applications. Preclinical validation is foundational to the translational process, and we will discuss the critical aspects of such animal studies. Finally, we will focus on the patient point-of-care and challenges in neuromodulation as the ultimate goal of bioelectronic medicine. This review is a call to scientists from different fields to work together with a common endeavor: accelerate the decoding and modulation of the nervous system in a new era of therapeutic possibilities.

Bioelectronic medicines aim to diagnose and treat a wide range of illnesses and ailments, including cancer, rheumatoid arthritis, inflammatory bowel disease, obesity, diabetes, asthma, paralysis, blindness, bleeding, ischemia, organ transplantation, cardiovascular disease, and neurodegenerative diseases. The focus of bioelectronic medicine is on electrical signaling of the nervous system. Understanding the nervous system's regulatory roles and developing technologies that record, activate, or inhibit neural signaling to influence particular biological pathways. Bioelectronic medicine is an emerging therapeutic option with the interconnection between molecular medicine, neuroscience, and bioengineering. The creation of nerve stimulating devices that communicate with both the central and peripheral nervous systems has the potential to completely transform how we treat disorders. Although early clinical applications have been largely effective across entire nerves, the ultimate goal is to create implantable, miniature closed-loop systems that can precisely identify and modulate individual nerve fibers to treat a wide range of disorders. The data bases such as PubMed, and Clinicaltrial.gov.in were searched for scientific research, review and clinical trials on bioelectronic medicine. The field of bioelectronic medicine is trending at present. In recent years, researchers have extended the field's applications, undertaken promising clinical trials, and begun delivering therapies to patients, thus creating the groundwork for significant future advancements. Countries and organizations must collaborate across industries and regions to establish an atmosphere and guidelines that foster the advancement of the field and the fulfillment of its prospective advantages.

Recording neural signals from delicate autonomic nerves is a challenging task that requires the development of a low-invasive neural interface with highly selective, micrometer-sized electrodes. This paper reports on the development of a three-dimensional (3D) protruding thin-film microelectrode array (MEA), which is intended to be used for recording low-amplitude neural signals from pelvic nervous structures by penetrating the nerves transversely to reduce the distance to the axons. Cylindrical gold pillars (Ø 20 or 50 µm, ~60 µm height) were fabricated on a micromachined polyimide substrate in an electroplating process. Their sidewalls were insulated with parylene C, and their tips were optionally modified by wet etching and/or the application of a titanium nitride (TiN) coating. The microelectrodes modified by these combined techniques exhibited low impedances (~7 kΩ at 1 kHz for Ø 50 µm microelectrode with the exposed surface area of ~5000 µm²) and low intrinsic noise levels. Their functionalities were evaluated in an ex vivo pilot study with mouse retinae, in which spontaneous neuronal spikes were recorded with amplitudes of up to 66 µV. This novel process strategy for fabricating flexible, 3D neural interfaces with low-impedance microelectrodes has the potential to selectively record neural signals from not only delicate structures such as retinal cells but also autonomic nerves with improved signal quality to study neural circuits and develop stimulation strategies in bioelectronic medicine, e.g., for the control of vital digestive functions.

<p>Takotsubo syndrome (TTS) is usually triggered by psychological or physical stress. One of the many physical sources of stress are central nervous system (CNS) disorders. CNS disorders most frequently triggering TTS include subarachnoid bleeding, epilepsy, ischemic stroke, migraine, and intracerebral bleeding. More rare CNS-triggers of TTS include posterior reversible encephalopathy syndrome (PRES), amyotrophic lateral sclerosis, encephalitis, or traumatic brain or spinal cord injury. TTS triggered by any of the CNS disorders needs to be recognized since adequate treatment of TTS may improve the general outcome from the CNS disorder as well. Neurologists need to be aware of TTS as a complication of specific CNS disorders but TTS may be triggered also by CNS disorders so far not recognised as causes of TTS.</p>

Neural prosthesis is based on brain-computer interface (BCI), which directly acts on the muscle system or an external device by analyzing EEG control commands, so as to compensate the efferent pathway of brain-spinal cord-muscle and recover motor function of patients with spinal cord injury. The technology involves comprehensive research of multiple disciplines such as brain science, cognitive neuroscience, biomedical engineering, information and communication engineering, control science and engineering. This paper reviews recent advances of neural prosthesis in the rehabilitation treatment of patients with spinal cord injury. DOI: 10.3969/j.issn.1672-6731.2017.06.002

Cannabis-Based Medicines ??? GW Pharmaceuticals

Central nervous system (CNS) disorders, such as ischemic stroke, Alzheimer’s disease, Parkinson’s disease, spinal cord injury, glioma, and epilepsy, involve oxidative stress and neuronal apoptosis, often leading to long-term disability or death. Emerging studies suggest that oxidative stress may induce epigenetic modifications that contribute to CNS disorders. Non-coding RNAs are epigenetic regulators involved in CNS disorders and have attracted extensive attention. Long non-coding RNAs (lncRNAs) are non-coding RNAs more than 200 nucleotides long and have no protein-coding function. However, these molecules exert regulatory functions at the transcriptional, post-transcriptional, and epigenetic levels. However, the major role of lncRNAs in the pathophysiology of CNS disorders, especially related to oxidative stress, remains unclear. Here, we review the molecular functions of lncRNAs in oxidative stress and highlight lncRNAs that exert positive or negative roles in oxidation/antioxidant systems. This review provides novel insights into the therapeutic potential of lncRNAs that mediate oxidative stress in CNS disorders.

In the absence of approved treatments to repair damage to the central nervous system, the role of neurosurgeons after spinal cord injury (SCI) often remains confined to spinal cord decompression and vertebral fracture stabilization. However, recent advances in bioelectronic medicine are changing this landscape. Multiple neuromodulation therapies that target circuits located in the brain, midbrain, or spinal cord have been able to improve motor and autonomic functions. The spectrum of implantable brain-computer interface technologies is also expanding at a fast pace, and all these neurotechnologies are being progressively embedded within rehabilitation programs in order to augment plasticity of spared circuits and residual projections with training. Here, we summarize the impending arrival of bioelectronic medicine in the field of SCI. We also discuss the new role of functional neurosurgeons in neurorestorative interventional medicine, a new discipline at the intersection of neurosurgery, neuro-engineering, and neurorehabilitation.

Modulation of the peripheral nervous system (PNS) has a great potential for therapeutic intervention as well as restore bodily functions. Recent interest has focused on autonomic nerves, as they regulate extensive functions implicated in organ physiology, chronic disease state and appear tractable to targeted modulation of discrete nerve units. Therapeutic interventions based on specific bioelectronic neuromodulation depend on reliable neural interface to stimulate and record autonomic nerves. Furthermore, the function of stimulation and recording requires energy which should be delivered to the interface. Due to the physiological and anatomical challenges of autonomic nerves, various forms of this active neural interface need to be developed to achieve next generation of neural interface for bioelectronic medicine. In this article, we present an overview of the state-of-the-art for peripheral neural interface technology in relation to autonomic nerves. Also, we reveal the current status of wireless neural interface for peripheral nerve applications. Recent studies of a novel concept of self-sustainable neural interface without battery and electronic components are presented. Finally, the recent results of non-invasive stimulation such as ultrasound and magnetic stimulation are covered and the perspective of the future research direction is provided.