Search

Abstract Neural interfaces are bioelectronic devices capable of stimulating a population of neurons or nerve fascicles and recording electrical signals in a specific area. Despite their success in restoring sensory-motor functions in people with disabilities, their long-term exploitation is still limited by poor biocompatibility, mechanical mismatch between the device and neural tissue and the risk of a chronic inflammatory response upon implantation. In this context, the use of nature-derived materials can help address these issues. Examples of these materials, such as extracellular matrix proteins, peptides, lipids and polysaccharides, have been employed for decades in biomedical science. Their excellent biocompatibility, biodegradability in the absence of toxic compound release, physiochemical properties that are similar to those of human tissues and reduced immunogenicity make them outstanding candidates to improve neural interface biocompatibility and long-term implantation safety. The objective of this review is to highlight progress and challenges concerning the impact of nature-derived materials on neural interface design. The use of these materials as biocompatible coatings and as building blocks of insulation materials for use in implantable neural interfaces is discussed. Moreover, future perspectives are presented to show the increasingly important uses of these materials for neural interface fabrication and their possible use for other applications in the framework of neural engineering.

Vagus nerve stimulation (VNS) suppresses inflammation and autoimmune diseases in preclinical and clinical studies. The underlying molecular, neurological, and anatomical mechanisms have been well characterized using acute electrophysiological stimulation of the vagus. However, there are several unanswered mechanistic questions about the effects of chronic VNS, which require solving numerous technical challenges for a long-term interface with the vagus in mice. Here, we describe a scalable model for long-term VNS in mice developed and validated in four research laboratories. We observed significant heart rate responses for at least 4 weeks in 60–90% of animals. Device implantation did not impair vagus-mediated reflexes. VNS using this implant significantly suppressed TNF levels in endotoxemia. Histological examination of implanted nerves revealed fibrotic encapsulation without axonal pathology. This model may be useful to study the physiology of the vagus and provides a tool to systematically investigate long-term VNS as therapy for chronic diseases modeled in mice.

Closed-loop charge balancers make a considerable contribution to a safe and secure electrical stimulation and additionally present an alternative to bulky blocking capacitors. This CMOS-integrated, 22 V compliant Twin-Track active charge balancer accomplishes both instantaneous and long-term balanced conditions. Long-term charge balancing is achieved by a cause-based PI-controlled offset compensation of the remaining electrode voltage. A $G_{\mathrm{ m}}$ of only 1.5 nS offers a large (8 ms) time constant with only a 12 pF capacitor and leads to the first integrated PI-controller for offset compensation in neural implants. Instantaneous autonomous balancing is realized by a second concept, the consequence-based Inter-Pulse Charge Control. It uses a class-B architecture to supply the compensation currents. Thus, no additional references are required to define the safety window of the remaining electrode voltage. It consumes 31.8 ${\mu }\text{W}$ in the idle state, while the delivered output power can be as high as 11 mW. The two complementary approaches can be combined to one system, providing the opportunity to achieve a better performance. The system consumes 56 ${\mu }\text{W}$ and features a 36% mismatch correction in biphasic stimuli amplitude, as well as an autonomous 100% charge removal at maximum compensation amplitudes of 500 ${\mu }\text{A}$ , which makes it a suitable complement to monophasic stimulators. [ABSTRACT FROM AUTHOR]

A variety of metallic components have been used in medical devices where lifelong durability and physical strength are demanded. To investigate the in vivo changes of implanted metallic medical devices in humans, stainless steel sternal wires removed from patients were evaluated. Stainless steel (316L) sternal wires removed from four patients after 10, 13, 22, and 30 years of implantation were evaluated using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Macroscopically, the removed specimens maintained their metallic luster and color. Under SEM, small holes were observed sporadically at 10 years and they tended to connect in the drawing direction. The longer the implanted duration, the more numerous and deeper were the crevices observed. By EDS, sulfur, phosphorus, and calcium were identified in all areas at 10 years, in addition to the component elements of stainless steel, comprising iron, chromium, nickel, and manganese. Corrosion products observed at 30 years were identified as calcium phosphate. In conclusion, stainless steel sternal wires develop corroded pores that grow larger and deeper with time after implantation; however, the pores remain shallow even after decades of implantation and they may not be a cause of mechanical failure. An amount of metal ions equivalent to the corroded volume must have been released into the human body, but the effect of these metal ions on the body is not apparent. [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) suppresses inflammation and autoimmune diseases in preclinical and clinical studies. The underlying molecular, neurological, and anatomical mechanisms have been well characterized using acute electrophysiological stimulation of the vagus. However, there are several unanswered mechanistic questions about the effects of chronic VNS, which require solving numerous technical challenges for a long-term interface with the vagus in mice. Here, we describe a scalable model for long-term VNS in mice developed and validated in four research laboratories. We observed significant heart rate responses for at least 4 weeks in 60-90% of animals. Device implantation did not impair vagus-mediated reflexes. VNS using this implant significantly suppressed TNF levels in endotoxemia. Histological examination of implanted nerves revealed fibrotic encapsulation without axonal pathology. This model may be useful to study the physiology of the vagus and provides a tool to systematically investigate long-term VNS as therapy for chronic diseases modeled in mice., Competing Interests: IM, JH, NJ, DT, UA, EP, YC, AA, TD, EC, TZ, SL, RF, CW, YA, SZ No competing interests declared, KT holds patents broadly related to this work. He has assigned all rights to the Feinstein Institutes for Medical Research., (© 2021, Mughrabi et al.)