CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Jiamei Xiao,Jie Ding,Zhuoting Yu,Jiaze Gao,Mingze Zeng,Xiaoyang Wu,Borui Su,Chengheng Wu,Dan Wei,Jing Sun,Hongsong Fan
Peripheral nerve injury (PNI) is a common clinical complication of diabetes, however, lacks effective clinical treatment due to complex pathological microenvironment. Considering both biomimetic remodeling and pathological reversal, we proposed a boronic ester bonding integrated strategy to develop dextran-based hydrogel patch with dopamine methacrylate-conjugated exosomes (mExo) immobilization. Aldehyde/phenylboronic acid difunctional dextran was synthesized to establish hydrogel skeleton and provide self-adhesion and ROS/glucose modulation capacities for neuroprotection. Meanwhile, mExo as therapeutic factors were immobilized into hydrogels via boronic ester bonding and released in pathologic response to target mitochondrial dysfunction and achieve neurotherapy. Through in vitro assays, the composite hydrogel patch was shown to reduce oxidative stress by ROS scavenging, thereby protecting the mitochondrial morphological and functional homeostasis of healthy RSC96 cells. Indeed, the sustained released exosome conjugates regulated bioenergy metabolism and alleviated mitochondrial dysfunction in hyperglycemia damaged RSC96 cells by the up-regulated expression of E-cadherin and AMPK proteins. In vivo experiments proved that through correcting diabetic pathology and targeted treatment of damaged mitochondria, the hydrogel patch inhibited neuronal apoptosis and finally promoted axon regeneration, remyelination and motor function recovery after PNI in diabetic rats. The synergistic “two-pronged” strategy of biomimetic remodeling and pathological reversal opens a promising opportunity for non-invasive treatment of diabetic PNI.
研究领域:
生物医学工程
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再生医学
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糖尿病治疗
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产品关联
DOI
高影响因子
Journal of Integrative Medicine-JIM
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2025
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IF 4
Yan Zhang,Xin-yue Zhao,Meng-ting Liu,Zhu-chen Zhou,Hui-bin Cheng,Xu-hong Jiang,Yan-rong Zheng,Zhong Chen
Objective Treating peripheral nerve injury (PNI) presents a clinical challenge due to limited axon regeneration. Strychni Semen, a traditional Chinese medicine, is clinically used for numbness and hemiplegia. However, its role in promoting functional recovery after PNI and the related mechanisms have not yet been systematically studied. Methods A mouse model of sciatic nerve crush (SNC) injury was established and the mice received drug treatment via intragastric gavage, followed by behavioral assessments (adhesive removal test, hot-plate test and Von Frey test). Transcriptomic analyses were performed to examine gene expression in the dorsal root ganglia (DRGs) from the third to the sixth lumbar vertebrae, so as to identify the significantly differentially expressed genes. Immunofluorescence staining was used to assess the expression levels of superior cervical ganglia neural-specific 10 protein (SCG10). The ultra-trace protein detection technique was used to evaluate changes in gene expression levels. Results Strychni Semen and its active compounds (brucine and strychnine) improved functional recovery in mice following SNC injury. Transcriptomic data indicated that Strychni Semen and its active compounds initiated transcriptional reprogramming that impacted cellular morphology and extracellular matrix remodeling in DRGs after SNC, suggesting potential roles in promoting axon regeneration. Imaging data further confirmed that Strychni Semen and its active compounds facilitated axon regrowth in SNC-injured mice. By integrating protein–protein interaction predictions, ultra-trace protein detection, and molecular docking analysis, we identified myeloperoxidase as a potentially critical factor in the axon regenerative effects conferred by Strychni Semen and its active compounds. Conclusion Strychni Semen and its active compounds enhance sensory function by promoting axonal regeneration after PNI. These findings establish a foundation for the future applications of Strychni Semen and highlight novel therapeutic strategies and drug targets for axon regeneration. Please cite this article as: Zhang Y, Zhao XY, Liu MT, Zhou ZC, Cheng HB, Jiang XH, Zheng YR, Chen Z. Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia. J Integr Med . 2025; Epub ahead of print.
研究领域:
神经科学
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中药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2024
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IF 8
Jiamei Xiao,Zhuoting Yu,Yuan Tian,Mingze Zeng,Borui Su,Jie Ding,Chengheng Wu,Dan Wei,Jing Sun,Hongsong Fan
Nerve conduit is an alternative strategy in peripheral nerve injuries (PNI) treatment both for neural signals recording and therapeutic electrical stimulation (ES). Most conventional conduits suffer from surgical suturing and lacking real-time insights of nerve recovery, as well as failing in integrating therapy strategies. Herein, we introduce a bi-layered hydrogel conduit with microneedles (BHCM), in which poly (N-isopropylacrylamide) (PNIPAm)-incorporated polyethyleneimine (PEI) forms the outer layer for conductivity and electro-driven drug loading and release, whereas PNIPAm/alginate/tannic acid hydrogel (PNIPAm/SA/TA) forms the inner layer to ensure biocompatible mechanics and strong tissue adhesion. Meanwhile, the differences in doping manipulated different critical solution temperature (LCST) and swelling between the double layers determine the self-curling performance. Therefore, the BHCM responds to temperature and self-curls into conduit to wrap and bind to sciatic nerve, avoiding the complicated suturing and enhancing the interfacial electrical transmission. By puncturing the epineurium, the microneedles strongly enhance the electrochemical performance, and synergistically facilitate controllable drug delivery as well as electrical stimulation and recording efficiency. Further, BHCM is demonstrated to regulate macrophage polarization from M1 to M2 through electrically stimulated Rhein release, thereby reducing inflammation and facilitating diabetic PNI repair. The present design aims to improve biosafety, surgical simplicity to realize overall recovery of injured nerves, making it a promising candidate for advanced peripheral nerve repair strategies.
研究领域:
生物医学工程
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神经科学
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材料科学
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产品关联
DOI
高影响因子
Bioactive Materials
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2021
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IF 14.593
Can Liu,Lei Fan,Zhenming Tian,Huiquan Wen,Lei Zhou,Pengfei Guan,Yian Luo,Chuncheung Chan,Guoxin Tan,Chengyun Ning,Limin Rong,Bin Liu
Conductive scaffolds have been shown to exert a therapeutic effect on patients suffering from peripheral nerve injuries (PNIs). However, conventional conductive conduits are made of rigid structures and have limited applications for impaired diabetic patients due to their mechanical mismatch with neural tissues and poor plasticity. We propose the development of biocompatible electroconductive hydrogels (ECHs) that are identical to a surgical dressing in this study. Based on excellent adhesive and self-healing properties, the thin film-like dressing can be easily attached to the injured nerve fibers, automatically warps a tubular structure without requiring any invasive techniques. The ECH offers an intimate and stable electrical bridge coupling with the electrogenic nerve tissues. The in vitro experiments indicated that the ECH promoted the migration and adhesion of the Schwann cells. Furthermore, the ECH facilitated axonal regeneration and remyelination in vitro and in vivo through the MEK/ERK pathway, thus preventing muscle denervation atrophy while retaining functional recovery. The results of this study are likely to facilitate the development of non-invasive treatment techniques for PNIs in diabetic patients utilizing electroconductive hydrogels.
研究领域:
生物医学工程
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神经科学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2024
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IF 9.4
Yuye Huang,Kai Ye,Andong He,Shaobo Wan,Miaoben Wu,Donghao Hu,Kailei Xu,Peng Wei,Jun Yin
Peripheral nerve injuries (PNIs) can cause neuropathies and significantly affect the patient's quality of life. Autograft transplantation is the gold standard for conventional treatment; however, its application is limited by nerve unavailability, size mismatch, and local tissue adhesion. Tissue engineering, such as nerve guidance conduits, is an alternative and promising strategy to guide nerve regeneration for peripheral nerve repair; however, only a few conduits could reach the high repair efficiency of autografts. The healing process of PNI is frequently accompanied by not only axonal and myelination regeneration but also angiogenesis, which initializes nerve regeneration through vascular endothelial growth factor A (VEGF-A). In this study, a composite nerve conduit with a poly (lactic-co-glycolic acid) (PLGA) hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with VEGF-A transfected Schwann cells (SCs) as the inner layer was established to evaluate its promising ability for peripheral nerve repair. A rat model of peripheral nerve defect was used to examine the efficiency of PLGA/GelMA-SC (VA) conduits, whereas autograft, PLGA, PLGA/GelMA, and PLGA/GelMA-SC (NC) were used as controls. VEGF-A-transfected SCs can provide a stable source for VEGF-A secretion. Furthermore, encapsulation in GelMA cannot only promote proliferation and tube formation of human umbilical vein endothelial cells but also enhance dorsal root ganglia and neuronal cell extension. Previous animal studies have demonstrated that the regenerative effects of PLGA/GelMA-SC (VA) nerve conduit were similar to those of autografts and much better than those of other conduits. These findings indicate that combination of VEGF-A-overexpressing SCs and PLGA/GelMA conduit-guided peripheral nerve repair provides a promising method that enhances angiogenesis and regeneration during nerve repair. Statement of significance Nerve guidance conduits shows promise for peripheral nerve repair, while achieving the repair efficiency of autografts remains a challenge. In this study, a composite nerve conduit with a PLGA hollow tube as the outer layer and gelatin methacryloyl (GelMA) encapsulated with vascular endothelial growth factor A (VEGF-A)-transfected Schwann cells (SCs) as the inner layer was established to evaluate its potential ability for peripheral nerve repair. This approach preserves growth factor bioactivity and enhances material properties. GelMA insertion promotes Schwann cell proliferation and morphology extension. Moreover, transfected SCs serve as a stable VEGF-A source and fostering angiogenesis. This study offers a method preserving growth factor efficacy and safeguarding SCs, providing a comprehensive solution for enhanced angiogenesis and nerve regeneration.
研究领域:
组织工程
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神经科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Li Wang,Tao Gu,Chunguang Yu,Yingying Gao,Tingting Xuan,Kaichun Shen,Guowei Wang,Zhenhai Wang
Kaempferol (Kae) is a flavonoid that has antioxidant, anti-inflammatory and neuroprotective effects. In recent years, there have been increasing reports on viral infection-induced Guillain-Barré syndrome (GBS) with high rates of disability and fatality. Therefore, in order to search for effective peripheral nerve injury repair drugs, we used rats with experimental autoimmune neuritis (EAN) as the typical animal model for GBS, and implemented Kae treatment intervention on EAN rats. Real-time quantitative polymerase chain reaction (qPCR), western blotting (WB) and immunofluorescence (IF) were utilized to detect the changes of inflammatory factors and signaling pathway proteins in peripheral nerve of rats. The impact of Kae on peripheral nerve damage in EAN rats was evaluated in multiple dimensions by clinical symptom score and neuroelectrophysiology examination, and the protective impact and mechanism of Kae on peripheral nerve injury were revealed. Our results showed that Kae increased the expression of sciatic myelin basic protein (MBP), decreased the expression of peripheral nerve macrophage infiltration and inflammatory cytokines, including TNF-α, IL-1β and IL-6, and down-regulated the expression levels of TNFR1. Additionally, it suppressed the activation of the JNK and p38 pathways. It can alleviate sciatic nerve symptoms and pathological injury in EAN rats. Therefore, we believe that Kae can be used as an adjunct drug in the treatment of GBS.
研究领域:
药理学
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神经科学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2023
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IF 9.7
Mingxi Yang,Bang Su,Zhanchuan Ma,Xiaotian Zheng,Yan Liu,Yangfan Li,Jingyan Ren,Laijin Lu,Bai Yang,Xin Yu
Activation of autophagy in Schwann cells (SCs) has emerged as a powerful trigger for peripheral nerve injury (PNI) repair. Lithium ion (Li + ) is a classical autophagy activator that plays an important role in promoting axonal extension and remyelination . However, the therapeutic window of existing lithium drugs is extremely narrow, and the adverse side effects, especially nephrotoxicity, severely limit their therapeutic value. Herein, Li + -doped carbonized polymer dots (Li-CPDs) was synthesized for the first time to change the pharmacokinetics of Li + from occupying epithelial sodium channels to lipid raft-mediated endocytosis . The in-vivo results confirmed that Li-CPDs could accelerate the removal of myelin debris and promote nerve regeneration via activating autophagy of SCs. Moreover, Li-CPDs exhibited almost no renal toxicity compared to that of raw lithium drugs. Thus, Li-CPDs could serve as a promising Li + -based nanomedicine for PNI regeneration with improved biosafety. Statement of significance Regardless of the fact that lithium drugs have been used in treatment of mental illness such as manic depression, the systemic side effects and renal metabolic toxicity still seriously restrict their clinical application. Since Li + and Na + compete for ion channels of cell membrane , the cell entry efficiency is extremely low and easily affected by body fluctuations, which seems to be an unsolvable problem. Herein, we rationally exploited the endocytotic features of CPDs to develop Li-CPDs. The Li-CPDs improved the entry pathway, greatly reduced nephrotoxicity, and inherited the biological function of Li + to activate autophagy for promoting peripheral nerve regeneration. Due to the BBB-crossing property of Li-CPDs, it also showed application prospects in future research on central nervous system diseases.
研究领域:
纳米技术
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神经科学
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药理学
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生物材料
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产品关联
DOI
PubMed
高影响因子
Theranostics
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2020
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IF 8.579
Teng Ma,Yafeng Yang,Xin Quan,Lei Lu,Bing Xia,Jianbo Gao,Fengyu Qi,Shengyou Li,Laihe Zhao,Liangwei Mei,Yi Zheng,Yanbing Shen,Zhuojing Luo,Yan Jin,Jinghui Huang
Rationale: Local hypoxia is a challenge for fabrication of cellular grafts and treatment of peripheral nerve injury. In our previous studies, we demonstrated that perfluorotributylamine (PFTBA) could provide short term oxygen supply to Schwann cells (SCs) and counteract the detrimental effects of hypoxia on SCs during the early stages of nerve injury. However, the quick release of oxygen in PFTBA compromised its ability to counteract hypoxia over an extended time, limiting its performance in peripheral nerve injury. Methods: In this study, PFTBA-based oxygen carrier systems were prepared through coaxial electrospinning to prolong the time course of oxygen release. Core-shell structures were fabricated, optimized, and the oxygen kinetics of PFTBA-enriched core-shell fibers evaluated. The effect of core-shells on the survival and function of SCs was examined in both 2D and 3D systems as well as in vivo . The system was used to bridge large sciatic nerve defects in rats. Results: PFTBA core-shell fibers provided high levels of oxygen to SCs in vitro , enhancing their survival, and increasing NGF, BDNF, and VEGF expression in 2D and 3D culture systems under hypoxic condition. In vivo analysis showed that the majority of GFP-expressing SCs in the PFTBA conduit remained viable 14 days post-implantation. We found that axons in PFTBA oxygen carrier scaffold improved axonal regeneration, remyelination, and recovery. Conclusion: A synthetic oxygen carrier in core-shell fibers was fabricated by the coaxial electrospinning technique and was capable of enhancing SC survival and nerve regeneration by prolonged oxygen supply. These findings provide a new strategy for fabricating cellular scaffolds to achieve regeneration in peripheral nerve injury treatment and other aerobic tissue injuries.
研究领域:
组织工程
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神经科学
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生物材料
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再生医学
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DOI
PubMed
高影响因子
Bioactive Materials
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2025
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IF 20.3
Anmin Wang,Wenjing Song,Wentai Guo,Baolei Huang,Xingqiang Zhu,Hailin Zhang,Wei Zhai,Ye Tian,Li Ren
Peripheral nerve injuries remain a clinical challenge due to the limitations of autografts and unstable electrical signals in existing bioelectronic therapies. It is necessary to develop innovative strategies to achieve wireless, controllable peripheral neural regeneration (PNR). In this study, we developed a magneto-electric coupling-driven electroactive nerve guidance conduits (PCLG/AgNF NGCs) with a moving magnetic field (MMF) for PNR with wireless magneto-electric coupling electrical stimulation (MECES). PCLG/AgNF displayed high conductivity (25.48 ± 3.77 S/cm) and wireless controllability of generating electrical pulses (16.67 ± 0.47 μA to 475.7 ± 9.71 μA) with an MMF. The MECES produced by PCLG/AgNF with the MMF significantly promoted cell proliferation, cell migration, and upregulated the expression of β3-tubulin, neurofilament heavy chain and growth-associated protein 43, compared to PCLG/AgNF and MMF used individually. Mechanistically, we identified that PCLG/AgNF with the MMF activated the metabolism of taurine and hypotaurine corroborated by elevated intracellular taurine, which is crucial for MECES mediated repair processes. In a rat peripheral nerve defect model, the PCLG/AgNF NGCs with the MMF showed promising results in nerve regrowth, myelination, and functional recovery, performing comparably to autografts. This strategy offers PCLG/AgNF NGCs as a wireless, controllable, precision-enabled approach and provides novel insights for the effective PNR.
研究领域:
生物医学工程
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神经科学
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生物电子学
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组织工程
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2021
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IF 13.273
Jiao Jiao,Feng Wang,Jie-Jie Huang,Jin-Jian Huang,Zong-An Li,Yan Kong,Zhi-Jun Zhang
Peripheral nerve injury can lead to paralysis, chronic pain, muscle atrophy and disability due to interrupted bioelectric signal communications between spinal cord and the innervated bodies. Bioelectric materials, particularly conductive hydrogels, have shown the increasing potentials in neural engineering because they serve as tissue scaffolds that can support cell growth and differentiation, and restore functional electric conduction. In this work, we fabricated size-tunable microfluidic hollow fibers (HF) with improved stiffness and elasticity based on a triple network called SCPAPPy, which was composed of sodium alginate/Ca 2+ (SC), polyacrylamide (PA), and polypyrrole (PPy). This HF showed a higher conductivity of 0.32 S/m than that of native sciatic nerve. Based on finite element analysis and digital oscilloscope measurement, the conductive HF was demonstrated to generate electromotive forces through electromagnetic induction by using a figure-eight coil. This creative approach could non-invasively facilitate myelination by improving Schwann cell’s growth and migration. Meanwhile, the electromotive forces drove the secretion of endogenous nerve growth factor (NGF) from Schwann cells. Moreover, exogenous nerve growth factor-7S (NGF-7S) was loaded in the HF, which was released gradually and promoted the differentiation of neurons in a controlled manner. By applying the pulsed magnetic field (MF) and NGF-7S together, it was found that the rats with 5-mm sciatic nerve defects achieved a more rapid nerve regeneration and functional recovery. In a word, our study demonstrated the practical role of electromagnetic induction on nerve repair, and opened the window of synergistic therapy combining the bioelectricity and neurotrophic factors towards peripheral nerve injury.
研究领域:
生物医学工程
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神经工程
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组织工程
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Molecular Therapy-Nucleic Acids
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2023
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IF 8.8
Xinyi Gu,Shen Wang,Dongdong Li,Bo Jin,Zhidan Qi,Jin Deng,Chen Huang,Xiaofeng Yin
Peripheral nerve injury can lead to progressive muscle atrophy and poor motor function recovery, which is a difficult point of treatment, and the mechanism needs to be further explored. In previous studies we found that miR-142a-3p was significantly upregulated and persistently high expressed in denervated mouse skeletal muscle. Here, we show that overexpression of miR-142a-3p inhibited the growth and differentiation of C2C12 myoblast, while knockdown of miR-142a-3p had a promoting effect. In vitro, knockdown of miR-142a-3p in denervated mouse skeletal muscle effectively increased proliferating muscle satellite cells and ameliorated muscle atrophy. Mechanistically, the myoregulator Mef2a was proved to be an important downstream target of miR-142a-3p, and miR-142a-3p regulates skeletal muscle differentiation and regeneration by inhibiting the expression of Mef2a. The co-knockdown of Mef2a and miR-142a-3p effectively alleviated or offset the biological effects of miR-142a-3p knockdown. In conclusion, our data revealed that miR-142a-3p regulates neurogenic skeletal muscle atrophy by targeting Mef2a.
研究领域:
神经科学
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分子生物学
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肌肉骨骼疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2025
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IF 20.3
Long Lin,Xiaojing Yuan,Lili Ma,Liang Xu,Wenyue Xie,Ying Jiang,Jidong Xiu,Hongwei Xu,Zhuoling Tian,Jianan Qu,Chunhui Zhao,Zuoying Yuan,Huilin Liu,Jianyong Huang,Xing Wang
Local electrical stimulation (LES) is a widely used clinical method to treat peripheral nerve injury. However, existing plate electrodes (PE) usually suffer from low electronic transport efficiency, whereas acupuncture electrical stimulation may cause damage to normal tissues. There is an urgent need to develop an innovative LES technique with efficient electronic transport, minimal tissue injury and enhanced biosafety. Here, we present a new stretchable transcutaneous electrical stimulation system (STESS) that integrates dissolvable conductive microneedles (DCMN) for optimal skin penetration and electronic transport, along with snake-like electrodes that offer superior flexibility, which can effectively penetrate the stratum corneum, enabling deep tissue electrostimulation with minimal injury. In vitro studies and 3D finite-element analysis demonstrate that the DCMN-based electrotherapy significantly enhances subcutaneous nerve stimulation compared to the conventional PE-based technique. By diminishing the electrical resistance of the stratum corneum, the DCMN-based electrotherapy has shown remarkable in vivo therapeutic efficacy in a rat facial nerve crush injury model. This will pave the way for innovative physiotherapeutic methodologies in the realm of neurological rehabilitation.
研究领域:
生物医学工程
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神经科学
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康复医学
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微加工技术
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生物电子学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）