Stretchable, dynamic covalent polymers for soft, long-lived bioresorbable electronic stimulators designed to facilitate neuromuscular regeneration

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 25, 2020

Abstract Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, eliminate the need surgical extraction. Our findings overcome key challenges bioresorbable devices by realizing lifetimes match clinical needs. The exploit a dynamic covalent polymer facilitates tight bonding itself other surfaces, soft, elastic substrate encapsulation coating wireless components. We describe underlying features chemical design considerations this polymer, biocompatibility its constituent materials. In with optimized, designs, polymers enable stable, long-lived distal rat model peripheral nerve injuries, thereby demonstrating potential programmable long-term electrical stimulation maintaining muscle receptivity enhancing functional recovery.

Language: Английский

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Peripheral Nerve Injury Treatments and Advances: One Health Perspective

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(2), P. 918 - 918

Published: Jan. 14, 2022

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that lead to the loss of structure and/or function impairment. These changes cause partial or complete motor sensory functions, physical disability, neuropathic pain, which in turn affect quality life. This review aims revisit concepts associated with PNI anatomy peripheral is detailed explain different types injury. Then, some available therapeutic strategies are explained, including surgical methods, pharmacological therapies, use cell-based therapies alone combination biomaterials form tube guides. Nevertheless, even various treatments, it difficult achieve a perfect outcome functional recovery. enhance importance new especially severe lesions, overcome limitations better outcomes. The urge for approaches understanding methods evaluate regeneration fundamental from One Health perspective. In vitro models followed by vivo very important be able translate achievements human medicine.

Language: Английский

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Modulation of the Crosstalk between Schwann Cells and Macrophages for Nerve Regeneration: A Therapeutic Strategy Based on a Multifunctional Tetrahedral Framework Nucleic Acids System

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(46)

Published: April 28, 2022

Peripheral nerve injury (PNI) is currently recognized as one of the most significant public health issues and affects general well-being millions individuals worldwide. Despite advances in tissue engineering, repair still cannot guarantee complete functional recovery. In present study, an innovative approach adopted to establish a multifunctional tetrahedral framework nucleic acids (tFNAs) system, denoted MiDs, which can integrate powerful programmability, permeability, structural stability tFNAs, with regeneration potential microRNA-22 enhance communication between Schwann cells (SCs) macrophages for more effective rehabilitation peripheral nerves. Relevant results demonstrate that MiDs amplify ability SCs recruit facilitate their polarization into pro-healing M2 phenotype reconstruct post-injury microenvironment. Furthermore, initiate adaptive intracellular reprogramming within short period further promote axon remyelination. represent new possibility enhancing may have critical clinical applications future.

Language: Английский

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Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation

Antioxidants, Journal Year: 2022, Volume and Issue: 11(2), P. 408 - 408

Published: Feb. 17, 2022

Free radicals are formed as a part of normal metabolic activities but neutralized by the endogenous antioxidants present in cells/tissue, thus maintaining redox balance. This balance is disrupted certain neuropathophysiological conditions, causing oxidative stress, which implicated several progressive neurodegenerative diseases. Following neuronal injury, secondary injury progression also caused excessive production free radicals. Highly reactive radicals, mainly oxygen species (ROS) and nitrogen (RNS), damage cell membrane, proteins, DNA, triggers self-propagating inflammatory cascade degenerative events. Dysfunctional mitochondria under stress conditions considered key mediator neurodegeneration. Exogenous delivery holds promise to alleviate regain In this regard, natural synthetic have been evaluated. Despite promising results preclinical studies, clinical translation therapy treat diseases remains elusive. The issues could be their low bioavailability, instability, limited transport target tissue, and/or poor antioxidant capacity, requiring repeated high dosing, cannot administered humans because dose-limiting toxicity. Our laboratory investigating nanoparticle-mediated enzymes address some above issues. Apart from being endogenous, main advantage catalytic mechanism action; hence, they significantly more effective at lower doses detoxifying deleterious effects than nonenzymatic antioxidants. review provides comprehensive analysis potential therapy, challenges translation, role nanoparticles/drug systems play addressing these challenges.

Language: Английский

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Anisotropic scaffolds for peripheral nerve and spinal cord regeneration

Bioactive Materials, Journal Year: 2021, Volume and Issue: 6(11), P. 4141 - 4160

Published: April 23, 2021

The treatment of long-gap (>10 mm) peripheral nerve injury (PNI) and spinal cord (SCI) remains a continuous challenge due to limited native tissue regeneration capabilities. current clinical strategy using autografts for PNI suffers from source shortage, while the pharmacological SCI presents dissatisfactory results. Tissue engineering, as an alternative, is promising approach regenerating nerves cords. Through providing beneficial environment, scaffold primary element in engineering. In particular, scaffolds with anisotropic structures resembling extracellular matrix (ECM) can effectively guide neural outgrowth reconnection. this review, anatomy cords, well treatments SCI, first summarized. An overview critical components engineering status approaches are also discussed. Recent advances fabrication surface patterns, aligned fibrous substrates, 3D hydrogel scaffolds, their vitro vivo effects highlighted. Finally, we summarize potential mechanisms underlying architectures orienting axonal glial cell growth, along challenges prospects.

Language: Английский

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Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 17(10), P. 2185 - 2185

Published: Jan. 1, 2022

Previous studies on the mechanisms of peripheral nerve injury (PNI) have mainly focused pathophysiological changes within a single site. However, recent indicated that central nervous system, PNI can lead to in both sites and target organs at cellular molecular levels. Therefore, basic not been comprehensively understood. Although electrical stimulation was found promote axonal regeneration functional rehabilitation after PNI, as well alleviate neuropathic pain, specific successful treatment are unclear. We summarize discuss via stimulation. After activity system (spinal cord) is altered, which limit damaged nerve. For example, cell apoptosis synaptic stripping anterior horn spinal cord reduce speed regeneration. The pathological posterior modulate sensory abnormalities PNI. This be observed cases ectopic discharge dorsal root ganglion leading increased pain signal transmission. injured site also an important factor affecting post-PNI repair. proximal end sends out axial buds innervate skin muscle A slow axon leads low it take long time for reinnervate From perspective organs, long-term denervation cause atrophy corresponding skeletal muscle, abnormal perception hyperalgesia, finally, loss organ function. underlying use treat include inhibition stripping, addressing excessive excitability ganglion, alleviating improving neurological function, accelerating Electrical denervated recovery Findings from included confirm series physiological occur cord, site, dysfunction. may address mentioned above, thus promoting ameliorating

Language: Английский

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A 10-micrometer-thick nanomesh-reinforced gas-permeable hydrogel skin sensor for long-term electrophysiological monitoring

Science Advances, Journal Year: 2024, Volume and Issue: 10(2)

Published: Jan. 10, 2024

Hydrogel-enabled skin bioelectronics that can continuously monitor health for extended periods is crucial early disease detection and treatment. However, it challenging to engineer ultrathin gas-permeable hydrogel sensors self-adhere the human long-term daily use (>1 week). Here, we present a ~10-micrometer-thick polyurethane nanomesh-reinforced sensor continuous high-quality electrophysiological monitoring 8 days under life conditions. This research involves two key steps: (i) material design by gelatin-based thermal-dependent phase change hydrogels (ii) robust thinness geometry achieved through nanomesh reinforcement. The resulting exhibit thickness of ~10 micrometers with superior mechanical robustness, high adhesion, gas permeability, anti-drying performance. To highlight potential applications in treatment leverage collective features, demonstrate long-term, high-precision conditions up days.

Language: Английский

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Schwann Cell Role in Selectivity of Nerve Regeneration

Cells, Journal Year: 2020, Volume and Issue: 9(9), P. 2131 - 2131

Published: Sept. 20, 2020

Peripheral nerve injuries result in the loss of motor, sensory and autonomic functions denervated segments body. Neurons can regenerate after peripheral axotomy, but inaccuracy reinnervation causes a permanent function that impairs complete recovery. Thus, understanding how regenerating axons respond to their environment direct growth is essential improve functional outcome patients with lesions. Schwann cells (SCs) play crucial role regeneration process, little known about contribution specific reinnervation. Here, we review mechanisms by which SCs differentially influence motor axons. Mature express modality-specific phenotypes have been associated promotion selective regeneration. These include molecular markers, such as L2/HNK-1 carbohydrate, expressed SCs, or neurotrophic profile denervation, differs remarkably between SC modalities. Other important factors several molecules implicated axon-SC interaction. This cell–cell communication through adhesion (e.g., polysialic acid) inhibitory MAG) contributes guiding growing targets. As many these be modulated, further research will allow design new strategies recovery injuries.

Language: Английский

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Contact Separation Triboelectric Nanogenerator Based Neural Interfacing for Effective Sciatic Nerve Restoration

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(22)

Published: Feb. 24, 2022

Abstract Peripheral nerve injuries represent one of the most common causes permanent disabilities. Therapeutic electrical stimulation has been widely used in neural regeneration for decades. Combined with implantation a cuff, several outcomes have proven effectiveness and feasibility neuroprosthetic applications. However, current strategy fails to complete repair. There is lack research on long‐term implantable nanogenerators neurostimulation scenario. Especially considering many disease models, those devices may not reach vitro simulative working setting. Thus, an implanted sciatic system that spontaneously generates biphasic electric pulses response rats’ movement developed. The signals generated by this device could stimulate injured cuff electrode. This work introduces self‐regulated contact separation triboelectric nanogenerator electrode compares it chronic therapeutic restoration effect. Neural function observed gait histological analysis. Moreover, upregulation growth associated protein 43 can be protentional target. potential clinical application facilitating closed‐loop energy harvesting stimulation.

Language: Английский

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Axonal Regeneration: Underlying Molecular Mechanisms and Potential Therapeutic Targets

Biomedicines, Journal Year: 2022, Volume and Issue: 10(12), P. 3186 - 3186

Published: Dec. 8, 2022

Axons in the peripheral nervous system have ability to repair themselves after damage, whereas axons central are unable do so. A common and important characteristic of damage spinal cord, brain, nerves is disruption axonal regrowth. Interestingly, intrinsic growth factors play a significant role regeneration injured nerves. Various such as proteomic profile, microtubule stability, ribosomal location, signalling pathways mark line between axons’ capacity for self-renewal. Unfortunately, glial scar development, myelin-associated inhibitor molecules, lack neurotrophic factors, inflammatory reactions among that restrict regeneration. Molecular cAMP, MAPK, JAK/STAT, ATF3/CREB, BMP/SMAD, AKT/mTORC1/p70S6K, PI3K/AKT, GSK-3β/CLASP, BDNF/Trk, Ras/ERK, integrin/FAK, RhoA/ROCK/LIMK, POSTN/integrin activated nerve injury considered players In addition aforementioned pathways, microRNAs, astrocytes also commendable participants this review, we discuss detailed mechanism each pathway along with key can be potentially valuable targets help achieve quick healing. We identify prospective could close knowledge gaps molecular underlying shed light on creation more powerful strategies encourage injury.

Language: Английский

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