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Molecules (Basel, Switzerland) May 2021The nervous system is a significant part of the human body, and peripheral nerve injury caused by trauma can cause various functional disorders. When the broken end... (Review)
Review
The nervous system is a significant part of the human body, and peripheral nerve injury caused by trauma can cause various functional disorders. When the broken end defect is large and cannot be repaired by direct suture, small gap sutures of nerve conduits can effectively replace nerve transplantation and avoid the side effect of donor area disorders. There are many choices for nerve conduits, and natural materials and synthetic polymers have their advantages. Among them, the nerve scaffold should meet the requirements of good degradability, biocompatibility, promoting axon growth, supporting axon expansion and regeneration, and higher cell adhesion. Polymer biological scaffolds can change some shortcomings of raw materials by using electrospinning filling technology and surface modification technology to make them more suitable for nerve regeneration. Therefore, polymer scaffolds have a substantial prospect in the field of biomedicine in future. This paper reviews the application of nerve conduits in the field of repairing peripheral nerve injury, and we discuss the latest progress of materials and fabrication techniques of these polymer scaffolds.
Topics: Animals; Biomedical Technology; Extracellular Matrix; Humans; Peripheral Nerves; Polymers; Tissue Engineering; Tissue Scaffolds
PubMed: 34063072
DOI: 10.3390/molecules26092712 -
Current Neuropharmacology 2021Peripheral nerve injury could lead to either impairment or a complete loss of function for affected patients, and a variety of nerve repair materials have been developed... (Review)
Review
Peripheral nerve injury could lead to either impairment or a complete loss of function for affected patients, and a variety of nerve repair materials have been developed for surgical approaches to repair it. Although autologous or autologous tissue-derived biomaterials remain preferred treatment for peripheral nerve injury, the lack of donor sources has led biomedical researchers to explore more other biomaterials. As a reliable alternative, xenogeneic decellularized extracellular matrix (dECM)-based biomaterials have been widely employed for surgical nerve repair. The dECM derived from animal donors is an attractive and unlimited source for xenotransplantation. Meanwhile, as an increasingly popular technique, decellularization could retain a variety of bioactive components in native ECM, such as polysaccharides, proteins, and growth factors. The resulting dECM-based biomaterials preserve a tissue's native microenvironment, promote Schwann cells proliferation and differentiation, and provide cues for nerve regeneration. Although the potential of dECM-based biomaterials as a therapeutic agent is rising, there are many limitations of this material restricting its use. Herein, this review discusses the decellularization techniques that have been applied to create dECM-based biomaterials, the main components of nerve ECM, and the recent progress in the utilization of xenogeneic dECM-based biomaterials through applications as a hydrogel, wrap, and guidance conduit in nerve tissue engineering. In the end, the existing bottlenecks of xenogeneic dECM-based biomaterials and developing technologies that could be eliminated to be helpful for utilization in the future have been elaborated.
Topics: Animals; Biocompatible Materials; Decellularized Extracellular Matrix; Extracellular Matrix; Humans; Peripheral Nerves; Tissue Scaffolds
PubMed: 33176651
DOI: 10.2174/1570159X18666201111103815 -
Free Radical Biology & Medicine May 2022Schwann cells (SCs) are the major glial cells in peripheral nervous system. They unsheathe and myelinate axons and play an essential role in peripheral nerve...
Schwann cells (SCs) are the major glial cells in peripheral nervous system. They unsheathe and myelinate axons and play an essential role in peripheral nerve regeneration. Several studies report that Parkin-mediated mitophagy is associated with various diseases. Melatonin promotes proliferation of central glial cells. Little is known about the effect of melatonin and Parkin-mediated mitophagy on peripheral nerve repair. In this study, using a rat model of a peripheral nerve injury (PNI) and in vitro model established by RSC96 cells treated with tert-butyl hydroperoxide (TBHP), we found that Parkin-mediated mitophagy can effectively reduce the production of mitochondrial reactive oxygen species (ROS), maintain the balance of mitochondrial membrane potential, maintain autophagic flux, and inhibit mitochondrial apoptosis. At the same time, we found that the increase of Parkin under stress is a manifestation of the RSC96 cells' resistance to oxidative stress to maintain RSC96 cells' balance. In our experiment, melatonin is similar to a Parkin agonist, up-regulating the expression of Parkin, enhancing all the positive results of Parkin in a stress state, such as inhibiting active oxygen production, maintaining autophagic flux, and inhibiting mitochondrial apoptosis. In addition, we design in vivo experiments to verify in In vitro experiments. In in vivo, melatonin promotes the expression of Parkin, maintains autophagic flux, inhibits apoptosis, promotes myelin regeneration, reduces the regeneration of collagen fibers around damaged tissues, and promotes peripheral nerve repair. When adenovirus was used to down-regulate the expression of Parkin, we found that all the positive effects of melatonin were attenuated. Collectively, these findings indicate that melatonin upregulates Parkin-mediated mitophagy and promotes peripheral nerve repair. The results provide a basis for development of effective drugs for PNI treatment.
Topics: Animals; Apoptosis; Melatonin; Membrane Potential, Mitochondrial; Mitophagy; Peripheral Nerves; Rats; Reactive Oxygen Species; Ubiquitin-Protein Ligases
PubMed: 35504358
DOI: 10.1016/j.freeradbiomed.2022.04.016 -
Hand (New York, N.Y.) Jan 2022Digital nerves will experience tension under normal daily activities, and understanding the amount of tension experienced in these nerves relates directly to the...
Digital nerves will experience tension under normal daily activities, and understanding the amount of tension experienced in these nerves relates directly to the necessary strength in nerve repairs. To begin quantification of tension, the tension borne by the median and digital nerves in cadaveric hands was quantified under conditions of finger hyperextension, nerve distraction, and finger flexion. Five cadaveric hands were mounted in a special fixture that allowed finger hyperextension and flexion and could apply known distractions while the tension borne by each digital nerve was measured. Sequential dissection exposed the digital nerves so that measurements of tension in the median, common, and proper digital nerves were conducted with finger hyperextension, nerve distraction, and finger flexion. Metacarpophalangeal (MCP) hyperextension of 30° created mean nerve tensions up to 0.64 N, 5 mm of nerve distraction created mean nerve tensions up to 1.23 N, and 90° of MCP flexion relieved up to a mean of 1.18 N of nerve tension. In situ tension is present in the median and digital nerves with digital motion. Finger hyperextension and nerve distraction produce tension, whereas finger flexion reduces tension. Existing nerve repairs are strong enough to withstand in situ nerve tensions produced by reasonable digital motion if the original nerve length is present.
Topics: Fingers; Humans; Peripheral Nerves; Range of Motion, Articular; Upper Extremity
PubMed: 32088987
DOI: 10.1177/1558944720906497 -
Journal of Neural Engineering Nov 2021Neuromodulation of visceral nerves is being intensively studied for treating a wide range of conditions, but effective translation requires increasing the efficacy and...
Neuromodulation of visceral nerves is being intensively studied for treating a wide range of conditions, but effective translation requires increasing the efficacy and predictability of neural interface performance. Here we use computational models of rat visceral nerve to predict how neuroanatomical variability could affect both electrical stimulation and recording with an experimental planar neural interface.We developed a hybrid computational pipeline,sceralervensembleecording andtimulation (ViNERS), to couple finite-element modelling of extracellular electrical fields with biophysical simulations of individual axons. Anatomical properties of fascicles and axons in rat pelvic and vagus nerves were measured or obtained from public datasets. To validate ViNERS, we simulated pelvic nerve stimulation and recording with an experimental four-electrode planar array.Axon diameters measured from pelvic nerve were used to model a population of myelinated and unmyelinated axons and simulate recordings of electrically evoked single-unit field potentials (SUFPs). Across visceral nerve fascicles of increasing size, our simulations predicted an increase in stimulation threshold and a decrease in SUFP amplitude. Simulated threshold changes were dominated by changes in perineurium thickness, which correlates with fascicle diameter. We also demonstrated that ViNERS could simulate recordings of electrically-evoked compound action potentials (ECAPs) that were qualitatively similar to pelvic nerve recording made with the array used for simulation.We introduce ViNERS as a new open-source computational tool for modelling large-scale stimulation and recording from visceral nerves. ViNERS predicts how neuroanatomical variation in rat pelvic nerve affects stimulation and recording with an experimental planar electrode array. We show ViNERS can simulate ECAPS that capture features of our recordings, but our results suggest the underlying NEURON models need to be further refined and specifically adapted to accurately simulate visceral nerve axons.
Topics: Action Potentials; Animals; Axons; Computer Simulation; Electric Stimulation; Nerve Tissue; Peripheral Nerves; Rats
PubMed: 34740201
DOI: 10.1088/1741-2552/ac36e2 -
Advanced Science (Weinheim,... Apr 2022The treatment of peripheral nerve defects has always been one of the most challenging clinical practices in neurosurgery. Currently, nerve autograft is the preferred... (Review)
Review
The treatment of peripheral nerve defects has always been one of the most challenging clinical practices in neurosurgery. Currently, nerve autograft is the preferred treatment modality for peripheral nerve defects, while the therapy is constantly plagued by the limited donor, loss of donor function, formation of neuroma, nerve distortion or dislocation, and nerve diameter mismatch. To address these clinical issues, the emerged nerve guide conduits (NGCs) are expected to offer effective platforms to repair peripheral nerve defects, especially those with large or complex topological structures. Up to now, numerous technologies are developed for preparing diverse NGCs, such as solvent casting, gas foaming, phase separation, freeze-drying, melt molding, electrospinning, and three-dimensional (3D) printing. 3D printing shows great potential and advantages because it can quickly and accurately manufacture the required NGCs from various natural and synthetic materials. This review introduces the application of personalized 3D printed NGCs for the precision repair of peripheral nerve defects and predicts their future directions.
Topics: Nerve Regeneration; Peripheral Nerves; Printing, Three-Dimensional; Tissue Scaffolds
PubMed: 35182046
DOI: 10.1002/advs.202103875 -
Magnetic Resonance in Medicine Oct 2021To demonstrate and validate electric field (E-field) calculation and peripheral nerve stimulation (PNS) prediction methods that are accurate, computationally efficient,... (Meta-Analysis)
Meta-Analysis
PURPOSE
To demonstrate and validate electric field (E-field) calculation and peripheral nerve stimulation (PNS) prediction methods that are accurate, computationally efficient, and that could be used to inform regulatory standards.
METHODS
We describe a simplified method for calculating the spatial distribution of induced E-field over the volume of a body model given a gradient coil vector potential field. The method is easily programmed without finite element or finite difference software, allowing for straightforward and computationally efficient E-field evaluation. Using these E-field calculations and a range of body models, population-weighted PNS thresholds are determined using established methods and compared against published experimental PNS data for two head gradient coils and one body gradient coil.
RESULTS
A head-gradient-appropriate chronaxie value of 669 µs was determined by meta-analysis. Prediction errors between our calculated PNS parameters and the corresponding experimentally measured values were ~5% for the body gradient and ~20% for the symmetric head gradient. Our calculated PNS parameters matched experimental measurements to within experimental uncertainty for 73% of ∆G estimates and 80% of SR estimates. Computation time is seconds for initial E-field maps and milliseconds for E-field updates for different gradient designs, allowing for highly efficient iterative optimization of gradient designs and enabling new dimensions in PNS-optimal gradient design.
CONCLUSIONS
We have developed accurate and computationally efficient methods for prospectively determining PNS limits, with specific application to head gradient coils.
Topics: Electric Stimulation; Electricity; Electromagnetic Fields; Head; Magnetic Resonance Imaging; Peripheral Nerves
PubMed: 34080744
DOI: 10.1002/mrm.28853 -
Theranostics 2022Peripheral nerve injury (PNI) caused by trauma, chronic disease and other factors may lead to partial or complete loss of sensory, motor and autonomic functions, as well... (Review)
Review
Peripheral nerve injury (PNI) caused by trauma, chronic disease and other factors may lead to partial or complete loss of sensory, motor and autonomic functions, as well as neuropathic pain. Biological activities are always accompanied by mechanical stimulation, and biomechanical microenvironmental homeostasis plays a complicated role in tissue repair and regeneration. Recent studies have focused on the effects of biomechanical microenvironment on peripheral nervous system development and function maintenance, as well as neural regrowth following PNI. For example, biomechanical factors-induced cluster gene expression changes contribute to formation of peripheral nerve structure and maintenance of physiological function. In addition, extracellular matrix and cell responses to biomechanical microenvironment alterations after PNI directly trigger a series of cascades for the well-organized peripheral nerve regeneration (PNR) process, where cell adhesion molecules, cytoskeletons and mechanically gated ion channels serve as mechanosensitive units, mechanical effector including focal adhesion kinase (FAK) and yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) as mechanotransduction elements. With the rapid development of tissue engineering techniques, a substantial number of PNR strategies such as aligned nerve guidance conduits, three-dimensional topological designs and piezoelectric scaffolds emerge expected to improve the neural biomechanical microenvironment in case of PNI. These tissue engineering nerve grafts display optimized mechanical properties and outstanding mechanomodulatory effects, but a few bottlenecks restrict their application scenes. In this review, the current understanding in biomechanical microenvironment homeostasis associated with peripheral nerve function and PNR is integrated, where we proposed the importance of balances of mechanosensitive elements, cytoskeletal structures, mechanotransduction cascades, and extracellular matrix components; a wide variety of promising tissue engineering strategies based on biomechanical modulation are introduced with some suggestions and prospects for future directions.
Topics: Humans; Mechanotransduction, Cellular; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Tissue Engineering; Tissue Scaffolds
PubMed: 35836812
DOI: 10.7150/thno.74571 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Mar 2021To review the research progress of peripheral nerve mismatch regeneration, and to provide reference for its related basic research and clinical treatment. (Review)
Review
OBJECTIVE
To review the research progress of peripheral nerve mismatch regeneration, and to provide reference for its related basic research and clinical treatment.
METHODS
The pathophysiology of peripheral nerve after injury, several main factors affecting the mismatch regeneration of peripheral nerve, and the fate of axon after mismatch regeneration were summarized by referring to the relevant literature at home and abroad in recent years.
RESULTS
Distal pathways and target organs can selectively affect the mismatch regeneration of peripheral nerves; different phenotypes of Schwann cells have different effects on the mismatch regeneration of peripheral nerves; studying the mechanism of action of exosomes from different Schwann cells on different types of axons can provide a new direction for solving the mismatch regeneration of peripheral nerves.
CONCLUSION
Peripheral nerve mismatch regeneration is affected by various factors. However, the specific mechanism and characteristics of these factors remain to be further studied.
Topics: Axons; Humans; Nerve Regeneration; Peripheral Nerve Injuries; Peripheral Nerves; Schwann Cells
PubMed: 33719250
DOI: 10.7507/1002-1892.202008085 -
Progress in Neurobiology Aug 2023Myelin improves axonal conduction velocity and is essential for nerve development and regeneration. In peripheral nerves, Schwann cells depend on bidirectional...
Myelin improves axonal conduction velocity and is essential for nerve development and regeneration. In peripheral nerves, Schwann cells depend on bidirectional mechanical and biochemical signaling to form the myelin sheath but the mechanism underlying this process is not understood. Rho GTPases are integrators of "outside-in" signaling that link cytoskeletal dynamics with cellular architecture to regulate morphology and adhesion. Using Schwann cell-specific gene inactivation in the mouse, we discovered that RhoA promotes the initiation of myelination, and is required to both drive and terminate myelin growth at different stages of peripheral myelination, suggesting developmentally-specific modes of action. In Schwann cells, RhoA targets actin filament turnover, via Cofilin 1, actomyosin contractility and cortical actin-membrane attachments. This mechanism couples actin cortex mechanics with the molecular organization of the cell boundary to target specific signaling networks that regulate axon-Schwann cell interaction/adhesion and myelin growth. This work shows that RhoA is a key component of a biomechanical response required to control Schwann cell state transitions for proper myelination of peripheral nerves.
Topics: Mice; Animals; Actins; Schwann Cells; Myelin Sheath; Peripheral Nerves; Axons
PubMed: 37315917
DOI: 10.1016/j.pneurobio.2023.102481