Bioactive Materials
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2022
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IF 16.874
Ruofei Wang,Xia-Xiao Wu,Zhenming Tian,Tian Hu,Chaoyang Cai,Guan-Ping Wu,Gang-Biao Jiang,Bin Liu
Spinal cord injury (SCI) results in massive neuronal death, axonal disruption, and cascading inflammatory response, which causes further damage to impaired neurons. The survived neurons with damaged function fail to form effective neuronal circuits. It is mainly caused by the neuroinflammatory microenvironment at injury sites and regenerated axons without guidance. To address this challenge, a ferrofluid hydrogel (FFH) was prepared with Ferric tetrasulfide (Fe 3 S 4 ), carboxymethyl chitosan, and gold. Its internal structural particles can be oriented in a magnetic field to acquire anisotropy. Moreover, Fe 3 S 4 can release hydrogen sulfide (H 2 S) with anti-inflammatory effects under acidic conditions. Regarding in vitro experiments, 0.01g/ml Fe 3 S 4 FFH significantly reduced the inflammatory factors produced by LPS-induced BV2 cells. Oriented and longer axons of the induced neural stem cells loaded on anisotropic FFH were observed. In vivo experiments showed that FFH reduced the activated microglia/macrophage and the expression of pro-inflammatory factors in SCI rats through the NF-κB pathway. Moreover, it significantly promoted directional axonal regrowth and functional recovery after SCI. Given the critical role of inhibition of neuroinflammation and directional axonal growth, anisotropic Fe 3 S 4 FFH is a promising alternative for the treatment of SCI.
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
PubMed
高影响因子
Journal of Integrative Medicine-JIM
·
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
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Bingqing Luo,Tingting Cheng,Ying Xiang,Shengkai Sun,Yuanshan Liu,Jincong Yan,Yajie Zhang,Yi Cao,Xingzhu Liu,Renjun Pei
Optic neuropathy, characterized by the irreversible degeneration of RGCs, leads to vision loss for which treatment options remained limited. Nanoparticle-based therapeutic strategies have been developed to stimulate RGCs regeneration; however, insufficient nanoparticles delivery to RGCs and a lack of robust stimulation of RGCs intrinsic regenerative capacity, have limited their application. Here, we demonstrate that a RGC-targeting Tet1 conjugated to liposome delivery system (Lipo-T) enhances therapeutic agent delivery to RGCs while minimizing off-target effect for activating glial cells. Targeted delivery of a mTOR-specific activator MHY1485 to RGCs via Lipo-T (MHY@Lipo-T) significantly enhances in vivo RGCs survival, neurite outgrowth, and axonal regeneration without retinal inflammation from unwanted glial activation. By conferring sustained MHY1485 to degenerated retina through Lipo-T injection, and with its high target ability potential, the first use of MHY@Lipo-T expands new therapeutic option for optic nerve injury.
研究领域:
神经科学
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药学
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眼科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-16
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IF 10.6
Li Chao,Xiang Zhenyang,Hou Mengfan,Yu Hao,Peng Peng,Lv Yigang,Ma Chao,Ding Han,Jiang Yunpeng,Liu Yang,Zhou Hengxing,Feng Shiqing
Background Spinal cord injury (SCI) often leads to a loss of motor and sensory function. Axon regeneration and outgrowth are key events for functional recovery after spinal cord injury. Endogenous growth of axons is associated with a variety of factors. Inspired by the relationship between developing nerves and blood vessels, we believe spinal cord-derived microvascular endothelial cells (SCMECs) play an important role in axon growth. Results We found SCMECs could promote axon growth when co-cultured with neurons in direct and indirect co-culture systems via downregulating the miR-323-5p expression of neurons. In rats with spinal cord injury, neuron-targeting nanoparticles were employed to regulate miR-323-5p expression in residual neurons and promote function recovery. Conclusions Our study suggests that SCMEC can promote axon outgrowth by downregulating miR-323-5p expression within neurons, and miR-323-5p could be selected as a potential target for spinal cord injury repair. Graphical Abstract
研究领域:
神经科学
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分子生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2016
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IF 2.326
Tongliang Xia,Bin Huang,Shilei Ni,Lei Gao,Jiangang Wang,Jian Wang,Anjing Chen,Shaowei Zhu,Benlin Wang,Gang Li,Shugan Zhu,Xingang Li
This study describes the use of poly(propylene carbonate) (PPC) electrospun microfibres impregnated with a combination of dibutyryl cyclic adenosine monophosphate (db-cAMP) and chondroitinase ABC (ChABC) in the treatment of right-side hemisected spinal cord injury (SCI). Release of db-cAMP and/or ChABC from the microfibres was assessed in vitro using high-performance liquid chromatography (HPLC). Drug-impregnated microfibres were implanted into the hemisected thoracic spinal cord of rats, and treatment was evaluated using functional recovery examinations and immunohistochemistry . Our results demonstrated that the microfibres containing db-cAMP and/or ChABC displayed a stable and prolonged release of each agent. Sustained delivery of db-cAMP and/or ChABC was found to promote axonal regenerative sprouting , functional recovery, and reduced glial scar formation when compared to untreated control animals. The combination of both db-cAMP and ChABC was determined to be more effective than using either drug alone in the treatment of SCI. These findings demonstrate the feasibility of using PPC electrospun microfibres for multi-drug combination therapy in SCI.
研究领域:
神经科学
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再生医学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Chen Xianghang,Wang Beini,Al Mamun Abdullah,Du Kaiyi,Wang Shengfu,Hu Qianqian,Chen Xinyuan,Lu Yang,Du Anyu,Wu Yueqi,Shao Jiaqin,Wang Shuangshuang,Jiang Chang,Zhou Kailiang,Hu Siwang,Xiao Jian
Introduction Spinal cord injury (SCI) impairs the balance of gut microbiomes, which further aggravates inflammation in the injured areas and inhibits axonal regeneration. The intestinal microbiome plays an important role in SCI and regulating intestinal microbiome promotes SCI repair. However, current studies have shown that indole-3 propionate (IPA), a metabolite of gut bacteria, can promote axonal regeneration. However, the short half-life of IPA limits its effectiveness. Gut microbiota plays a role in the progression of SCI, but the studies about diet regulates intestinal flora metabolites to improve SCI are still limited and lack guiding significance. Results The results showed that Pectin-Zein-IPA NPs treatment improves motor function recovery, inhibits the activation of oxidative stress, enhances axonal regeneration and activates AKT/Nrf-2 signaling pathway following SCI. Further analysis showed that Pec-Zein-IPA NPs treatment reduced the intestinal flora metabolite accumulation of L-methionine, and alleviated neuroinflammation by improving autophagy and inhibiting pyroptosis. Pec-Zein-IPA may reduced neuroinflammation after SCI by decreasing the abundance of Clostridia − UCG-014 , Clostridia − vadinBB60 − group , Shewanella (positively correlated with L-Methionine) and increasing the abundance of Parasutterella (negatively correlated with L-Methionine). Conclusions Our findings provide a strategy for oral drug research in SCI. The results suggest that Pectin-Zein-IPA NPs have potential advantages for treatment and management of SCI. Reducing L-methionine intake may help reduce neuroinflammation after SCI. Graphical
研究领域:
神经科学
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药理学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
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2025
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IF 5.7
Wenyong Gao,Can Tang,Diancheng Hang,Hao Chen,Dongsheng Li,Youjie Yan,Wuchang Wang,Hao Peng,Xianmin Wang,Enpeng Zhang,Min Wei,Hengzhu Zhang,Xiaodong Wang
Acute spinal cord injury (SCI) induces mitochondrial oxidative stress, cellular bioenergetic crises, impaired protein degradation, and subsequent degeneration, resulting in increased neuronal vulnerability. Transplantation of exogenous mitochondria to the injury site mitigates cellular energy crises and counteracts neurodegeneration; however, the limited efficacy of mitochondrial transplantation alone constrains its therapeutic potential. In this study, we established a right-sided spinal cord hemisection model at the T10 thoracic segment in rats and transplanted a methacrylate-based gelatin (GelMA) hydrogel containing active mitochondria at the injury site to assess its therapeutic effects and underlying mechanisms. Our findings indicate that GelMA hydrogel combined with mitochondrial transplantation provides superior therapeutic benefits for SCI compared to mitochondrial transplantation alone. GelMA hydrogel enables sustained mitochondrial release at the injury site, supplying energy, upregulating NF200 expression, and promoting axonal regeneration. Additionally, it enhances M2 macrophage accumulation and improves the local inflammatory microenvironment. The structural framework of GelMA hydrogel further supports axonal regeneration. Footprint gait analysis and Basso, Beattie, and Bresnahan (BBB) motor scoring demonstrated that GelMA hydrogel combined with mitochondrial transplantation significantly improves motor function in the right hind limb of rats with SCI. Consequently, GelMA hydrogel combined with mitochondrial transplantation offers a viable and promising approach for treating spinal cord injury.
研究领域:
神经科学
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生物材料
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再生医学
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细胞治疗
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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
Theranostics
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2019
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IF 8.063
Chenggui Wang,Zhe Gong,Xianpeng Huang,Jingkai Wang,Kaishun Xia,Liwei Ying,Jiawei Shu,Chao Yu,Xiaopeng Zhou,Fangcai Li,Chengzhen Liang,Qixin Chen
Rationale: Spinal cord injury (SCI) remains a critical clinical challenge. The controlled release of FGF4, a novel neuroprotective factor, from a versatile Laponite hydrogel to the injured site was a promising strategy to promote axon regeneration and motor functional recovery after SCI. Methods: Characterization of Laponite, Laponite/Heparin (Lap/Hep) and Laponite/Heparin loaded with FGF4 (Lap/Hep@FGF4) hydrogels were measured by rheometer. Multiple comprehensive evaluations were used to detect motor functional recovery and the axonal rehabilitation after Lap/Hep@FGF4 treatment in vivo (SCI rat model). Moreover, microtubule dynamic and energy transportation, which regulated axonal regeneration was evaluated by Lap/Hep@FGF4 gel in vitro (primary neuron). Results: FGF4 released from Lap/Hep gel locally achieves strong protection and regeneration after SCI. The Lap/Hep@FGF4 group revealed remarkable motor functional recovery and axonal regrowth after SCI through suppressing inflammatory reaction, increasing remyelination and reducing glial/fibrotic scars. Furthermore, the underlying mechanism of axonal rehabilitation were demonstrated via enhancing microtubule stability and regulating mitochondrial localization after Lap/Hep@FGF4 treatment. Conclusion: This promising sustained release system provides a synergistic effective approach to enhance recovery after SCI underlying a novel mechanism of axonal rehabilitation, and shows a translational prospect for the clinical treatment of SCI.
研究领域:
神经科学
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生物医学工程
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药理学
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产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2018
·Vol. 43
·期 3
·659-668
·
IF 2.772
Yang Xiaofan,Xue Pingping,Wei Ruozheng,Liu Xin,Xu Xiang,Liu Zhenyu,Chen Yanhua,Chen Zhenbing
Neuroactive steroids such as progesterone, testosterone, and their derivatives have been widely studied for their neuroprotective roles in the nervous system. Autologous nerve transplantation is considered as the gold standard repair technique when primary suture is impossible; nevertheless, this method is far from ideal. In this study, we aimed to explore the impact of dihydrotestosterone (DHT), a 5α-reduced derivative of testosterone, on the recovery of peripheral nerve injury treated with autologous nerve transplantation. Sprague–Dawley rats were subjected to a 10-mm right side sciatic nerve reversed autologous nerve transplantation and randomly divided into groups that received DHT or DHT + flutamide (an androgen receptor blocker) daily for 8 weeks after operation. Our results demonstrated that DHT could speed up the rate of axonal regeneration and increase the expression of myelin protein zero (P0) in autograft reversal sciatic nerves. Thus, our study provided new insights into improving the prognosis of patients with long gap peripheral nerve defects.
研究领域:
神经科学
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药理学
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再生医学
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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
Small
·
2024
·
IF 13
Sipin Zhu,Qiuji Wu,Yibo Ying,Yuqin Mao,Wenjie Lu,Jie Xu,Xiong Cai,Huacheng He,Jiang Wu
Spinal cord injury (SCI) is a severe clinical disease usually accompanied by activated glial scar, neuronal axon rupture, and disabled motor function. To mimic the microenvironment of the SCI injury site, a hydrogel system with a comparable mechanical property to the spinal cord is desirable. Therefore, a novel elastic bovine serum albumin (BSA) hydrogel is fabricated with excellent adhesive, injectable, and biocompatible properties. The hydrogel is used to deliver paclitaxel (PTX) together with basic fibroblast growth factor (bFGF) to inhibit glial scar formation as well as promote axon regeneration and motor function for SCI repair. Due to the specific interaction of BSA with both drugs, bFGF, and PTX can be controllably released from the hydrogel system to achieve an effective concentration at the wound site during the SCI regeneration process. Moreover, benefiting from the combination of PTX and bFGF, this bFGF/PTX@BSA system significantly aided axon repair by promoting the elongation of axons across the glial scar with reduced reactive astrocyte secretion. In addition, remarkable anti-apoptosis of nerve cells is evident with the bFGF/PTX@BSA system. Subsequently, this multi-functionalized drug system significantly improved the motor function of the rats after SCI. These results reveal that bFGF/PTX@BSA is an ideal functionalized material for nerve repair in SCI.
研究领域:
神经科学
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Zuoxiang Dong,Jihu Zhao,Wenshuai Deng,Congxiao Wang,Zhiguo Chen,Peng Sun
Spinal cord injury (SCI) often leads to severe and long-lasting disability, profoundly impacting both the physical and mental well-being of patients. While rehabilitation and regenerative medicine represent promising avenues for SCI recovery, their combined application remains underexplored. In this study, we developed a biodegradable, low-swelling, multi-ionic hydrogel composed of oxidized dextran (ODex), dopamine-grafted gelatin (DG), and a combination of essential ions (Ca 2+ , Mg 2+ , Zn 2+ , and Fe 3+ ). This hydrogel exhibits a suite of desirable properties, including optimal pore size, excellent biocompatibility, injectability, minimal swelling, strong adhesiveness, and notable antioxidative capacity. Functionally, the hydrogel can block calcium channels, reduce neuronal excitability, and alleviate muscle stiffness. At the cellular level, it supports neuronal growth and enhances antioxidative defense mechanisms. Behavioral assessments and electrophysiological studies in animals demonstrated that the multi-ionic hydrogel promotes the generation of new neurons, axonal regeneration, synaptogenesis of various neurotransmitters, and supports remyelination. The results showed significant functional recovery in rodents, particularly in motor and sensory functions, with remarkable improvement in urinary retention. This study suggests that multi-ionic hydrogels hold great potential as a strategy for spinal cord injury repair and neural regeneration, and may also provide hope for tissue regeneration in other medical conditions.
研究领域:
生物材料
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神经科学
·
组织工程
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再生医学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）