JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-18
·
IF 9.429
Chen Youlu,Chen Zuoguan,Duan Jianwei,Gui Liang,Li Huiyang,Liang Xiaoyu,Tian Xinxin,Liu Kaijing,Li Yongjun,Yang Jing
Peripheral vascular disease (PVD) is a common clinical manifestation of atherosclerosis. Vascular endothelial growth factor (VEGF) gene therapy is a promising approach for PVD treatment. However, due to single-gene therapy limitations and high H2O2 pathological microenvironment, VEGF gene therapy are not as expectations and its clinical application are limited. Synergistic effects of Nerve factors and vascular factors in angiogenesis have attracted attention in recent years. In this study, VEGF and nerve growth factor (NGF) genes co-delivery nanoparticles (VEGF/NGF-NPs) were prepared by using H2O2 responsive 6s-PLGA-Po-PEG as a carrier. 6s-PLGA-Po-PEG could react with H2O2 specifically due to the internal peroxalate bond. Angiogenic effects of VEGF/NGF-NPs has been evaluated in cells and hindlimb ischemia mice model. Results showed that VEGF/NGF-NPs promoted VEGF and NGF co-expression simultaneously, eliminated excessive H2O2, strengthened reactions between SH-SY5Ys and HUVECs, and finally enhanced migration, tube formation, proliferation and H2O2 damage resistance of HUVECs. VEGF/NGF-NPs also recovered blood perfusion, promoted the expression of VEGF, NGF, eNOS and NO, and enhanced vascular coverage of pericytes. Treatment effects of VEGF/NGF-NPs may related to VEGF/eNOS/NO pathway. Altogether, VEGF/NGF-NPs eliminated excessive H2O2 while achieving gene co-delivery, and promoted stable angiogenesis. It’s a promising way for PVD treatment by using VEGF/NGF-NPs.Graphical Abstract
研究领域:
生物医学工程
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分子生物学
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基因治疗
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血管医学
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产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2024
·Vol. 19
·期 1
·1-17
·
IF 2.8
Zhang Yong,Huang Wenliang,Xiao Hongli,Ruan Shiqiang,Deng Jiang
Background With the rapid growth of the ageing population, chronic diseases such as osteoarthritis have become one of the major diseases affecting the quality of life of elderly people. The main pathological manifestation of osteoarthritis is articular cartilage damage. Alleviating and repairing damaged cartilage has always been a challenge. The application of cartilage tissue engineering methods has shown promise for articular cartilage repair. Many studies have used cartilage tissue engineering methods to repair damaged cartilage and obtained good results, but these methods still cannot be used clinically. Therefore, this study aimed to investigate the effect of incorporating nerve growth factor (NGF) into a silk fibroin (SF)/chitosan (CS) scaffold containing bone marrow-derived mesenchymal stem cells (BMSCs) on the repair of articular cartilage defects in the knees of rabbits and to explore the possible underlying mechanism involved. Materials and methods Nerve growth factor-loaded sustained-release microspheres were prepared by a double emulsion solvent evaporation method. SF/CS scaffolds were prepared by vacuum drying and chemical crosslinking. BMSCs were isolated and cultured by density gradient centrifugation and adherent culture. NGF-SF/CS-BMSC composites were prepared and implanted into articular cartilage defects in the knees of rabbits. The repair of articular cartilage was assessed by gross observation, imaging and histological staining at different time points after surgery. The repair effect was evaluated by the International Cartilage Repair Society (ICRS) score and a modified Wakitani score. In vitro experiments were also performed to observe the effect of different concentrations of NGF on the proliferation and directional differentiation of BMSCs on the SF/CS scaffold. Results In the repair of cartilage defects in rabbit knees, NGF-SF/CS-BMSCs resulted in higher ICRS scores and lower modified Wakitani scores. The in vitro results showed that there was no significant correlation between the proliferation of BMSCs and the addition of different concentrations of NGF. Additionally, there was no significant difference in the protein and mRNA expression of COL2a1 and ACAN between the groups after the addition of different concentrations of NGF. Conclusion NGF-SF/CS-BMSCs improved the repair of articular cartilage defects in the knees of rabbits. This repair effect may be related to the early promotion of subchondral bone repair.
研究领域:
生物医学工程
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骨科
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
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
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Qingsong Jiang,Liaomin Zhou,Yi Yang,Hu Long,Liming Ge,Defu Li,Changdao Mu,Wenli Lai,Zhilang Xu,Yan Wang
The structural and functional repair of critical-sized irregular bone defect is still considered a serious challenge. Most bone implant materials used in current clinic are not able to induce reconstruction of functional neural network, which is the key in bone regeneration via neural-osteogenic pathway. In this study, we aimed to manufacture a novel injectable double-crosslinked collagen/hyaluronic acid hydrogel loaded with nerve growth factor (NGF), which was capable of well filling irregularly shaped bone defects and inducing reconstruction of neural network. Hyaluronic acid (HA) was sequentially oxidized by sodium periodate and modified by methacrylic anhydride to prepare methacrylated oxidized HA (MOH) as a crosslinker. Subsequently, the Collagen-MOH@NGF (CMHN) hydrogel was established by Schiff base reaction and double-bond photocrosslinking. Our results demonstrated the excellent microporous structure, injectable, self-healing, in-situ rapid crosslinking properties of CMHN hydrogel along with suitable mechanics, rheology, swelling, degradation and biocompatibility. Significantly, the introduction of NGF endowed CMHN hydrogel with better biological properties than that without NGF. In vitro , CMHN hydrogel promoted DRG neuron growth and osteogenic differentiation of BMSCs mediated by NGF-calcitonin gene-related peptide (CGRP) axis. In vivo , CMHN hydrogel possessed a better bone repair effect than free NGF and blank hydrogel, with a long-lasting NGF-promoting neuro-osteogenic action within 8 w in a rat cranial critical defect model. Overall, the prepared injectable NGF-loaded collagen/HA dual network hydrogel is a promising material to facilitate functional and structural repair of complex bone defects.
研究领域:
生物材料
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组织工程
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再生医学
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
NEUROCHEMICAL RESEARCH
·
2018
·Vol. 43
·期 7
·1439-1453
·
IF 2.772
Jia Jingjing,Zhang Ting,Chi Jieshan,Liu Xiaoma,Sun Jingjing,Xie Qizhi,Peng Sijia,Li Changyan,Yi Li
CeO 2 nanoparticles (nanoceria) have been used in many studies as a powerful free radical scavenger, and LXW7, a small-molecule peptide, can specifically target the integrin αvβ3, whose neuroprotective effects have also been demonstrated. The objective of this study is to observe the neuroprotective effect and potential mechanism of CeO 2 @PAA-LXW7, a new compound that couples CeO 2 @PAA (nanoceria modified with the functional group of polyacrylic acid) with LXW7 via a series of chemical reactions, in H 2 O 2 -induced NGF-differentiated PC12 cells. We examined the effects of LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 on the viability of primary hippocampal neurons and found that there was no significant difference under control conditions, but increased cellular viability was observed in the case of H 2 O 2 -induced injury. We used H 2 O 2 -induced NGF-differentiated PC12 cells as the classical injury model to investigate the neuroprotective effect of CeO 2 @PAA-LXW7. In this study, LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 inhibit H 2 O 2 -induced oxidative stress by reducing the production of reactive oxygen species (ROS) and regulating Bax/Bcl-2, cleaved caspase-3 and mitochondrial cytochrome C (cyto C) in the apoptotic signaling pathways. We found that the levels of phosphorylation of focal adhesion kinase (FAK) and of signal transducer and activator of transcription 3 (STAT3) increased significantly in H 2 O 2 -induced NGF-differentiated PC12 cells, whereas LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 suppressed the increase to different degrees. Among the abovementioned changes, the inhibitory effect of CeO 2 @PAA-LXW7 on H 2 O 2 -induced changes, including the increases in the levels of p-FAK and p-STAT3, is more obvious than that of LXW7 or CeO 2 @PAA alone. In summary, these results suggest that integrin signaling participates in the regulation of apoptosis via the regulation of ROS and of the apoptosis pathway in H 2 O 2 -induced NGF-differentiated PC12 cells. LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 can play neuroprotective roles by counteracting the oxidative stress and apoptosis induced by H 2 O 2 in NGF-differentiated PC12 cells. CeO 2 @PAA-LXW7 exerting a more powerful synergistic effect via the conjunction of LXW7 and CeO 2 @PAA.
研究领域:
神经科学
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药理学
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细胞生物学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2025
·
IF 3.6
Ling Peng,Yusong Pan,Qianqian Liu,Cuilian Wei,Run Huang,Wenjie Luo,Xiuling Lin,Jun Tao,Yinghai Xie
Spinal cord injury (SCI) is a common disease worldwide. Tissue engineering scaffolds are considered a promising strategy for SCI treatment, but their efficacy is significantly limited by the local abundance of MSC (mesenchymal stem cell) and a highly inflammatory microenvironment. In this study, a multifunctional composite scaffold of polycaprolactone/chitosan (PCL/CS) loading polydopamine (PDA)-coated nerve growth factor (NGF) loaded onto was prepared using a freeze-drying method. The PCL/CS composite scaffold exhibited tunable degradation properties and excellent biocompatibility. The PDA coating demonstrated potent free radical scavenging capabilities, achieving clearance rate of 90.65%, 77.53%, and 60.77% for DPPH, H2O2, and ·OH radicals, respectively. Remarkably, the scaffold effectively reduced intracellular ROS levels within 24 h under oxidative stress conditions. Flow cytometry revealed rapid cellular internalization, with the FITC-labeled PC-5-PDA group exhibiting a 99.87% FITC+ rate within 12 h. NGF release from the scaffold induced robust neuronal differentiation of PC-12 cells, as evidenced by a 58.1% increase in neurite length (from 104.77 μm at day 3 to 165.66 μm at day 4) and upregulated expression of microtubule-associated protein 2 (MAP2). These findings demonstrate the dual functionality of the scaffold, which is effectively modulating the post-SCI inflammatory microenvironment while promoting neural regeneration.
研究领域:
生物材料
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组织工程
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神经再生
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抗氧化治疗
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干细胞生物学
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产品关联
DOI
PubMed
高影响因子
Science Advances
·
2025
·Vol. 11
·期 12
·
IF 12.5
Kaicheng Xu,Kaile Wu,Liang Chen,Yubin Zhao,Hengyuan Li,Nong Lin,Zhaoming Ye,Jianbin Xu,Donghua Huang,Xin Huang
Sensory innervation triggers the regenerative response after injury. However, dysfunction and impairment of sensory nerves, accompanied by excessive inflammation impede tissue regeneration. Consequently, specific induction of sensory innervation to mediate immunoregulation becomes a promising therapeutic approach. Herein, we developed a cell/drug-free strategy to selectively boost endogenous sensory innervation to harness immune responses for promoting tissue rehabilitation. Specifically, a dual-functional phage was constructed with a sensory nerve–homing peptide and a β-subunit of nerve growth factor (β-NGF)–binding peptide. These double-displayed phages captured endogenic β-NGF and localized to sensory nerves to promote sensory innervation. Furthermore, regarding bone regeneration, phage-loaded hydrogels achieved rapid sensory nerve ingrowth in bone defect areas. Mechanistically, sensory neurotization facilitated M2 polarization of macrophages through the Sema3A/XIAP/PAX6 pathway, thus decreasing the M1/M2 ratio to induce the dissipation of local inflammation. Collectively, these findings highlight the essential role of sensory innervation in manipulating inflammation and provide a conceptual framework based on neuroimmune interactions for promoting tissue regeneration.
研究领域:
神经生物学
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免疫学
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再生医学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2021
·
IF 7.348
Luyu Wang,Dan Zhang,Yikun Ren,Shen Guo,Jinrui Li,Shanshan Ma,Minghao Yao,Fangxia Guan
Injectable hydrogel has the advantage to fill the defective area and thereby shows promise as therapeutic implant or cell/drug delivery vehicle for tissue repair. In this study, an injectable hyaluronic acid hydrogel in situ dual-enzymatically cross-linked by galactose oxidase (GalOx) and horseradish peroxidase (HRP) was synthesized and optimized, and the therapeutic effect of this hydrogel encapsulated with bone mesenchymal stem cells (BMSC) and nerve growth factors (NGF) for traumatic brain injury (TBI) mice was investigated. Results from in vitro experiments showed that either tyramine-modified hyaluronic acid hydrogels (HT) or NGF loaded HT hydrogels (HT/NGF) possessed good biocompatibility. More importantly, the HT hydrogels loaded with BMSC and NGF could facilitate the survival and proliferation of endogenous neural cells probably by neurotrophic factors release and neuroinflammation regulation, and consequently improved the neurological function recovery and accelerated the repair process in a C57BL/6 TBI mice model. All these findings highlight that this injectable, BMSC and NGF-laden HT hydrogel has enormous potential for TBI and other tissue repair therapy.
研究领域:
生物医学工程
·
神经科学
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组织工程
·
干细胞治疗
✓ 已验证
DOI
PubMed
高影响因子
Stem Cells International
·
2021
·
IF 5.443
Haixin Song,Tao Wu,Xiaotian Yang,Yangzheng Li,Ye Ye,Bo Li,Tao Liu,Shihui Liu,Jianhua Li
Late thrombosis and restenosis remain major challenges to the safety of drug-eluting stents. Biofunctional modification to endow the surface with selective anticoagulation and promote endothelium regeneration has become a hotpot recently. In this study, chitosan and heparin were found to form three-dimensional nanoparticles by spontaneous electrostatic interaction. Based on the specific binding properties between heparin and nerve growth factor (NGF), a new type of NGF-loaded heparin/chitosan nanoparticles was constructed for surface modification. The results of material characterization show that the nanoparticles are successfully immobilized on the surface of the material. In vitro blood compatibility and endothelial cell compatibility assay showed that the modified surface could selectively inhibit platelet adhesion and smooth muscle cell overproliferation, while accelerating endothelialization via promoting endothelial cell proliferation and enhancing endothelial progenitor cell mobilization.
研究领域:
生物材料学
·
心血管医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Infectious Diseases
·
2020
·
IF 4.614
Chongshan Dai,Xilong Xiao,Yuan Zhang,Biao Xiang,Daniel Hoyer,Jianzhong Shen,Tony Velkov,Shusheng Tang
Peripheral neurotoxicity often occurs in patients receiving parenteral polymyxin therapy (i.e., colistin methanesulfonate or polymyxin B). The present study aimed to investigate the protective effect of curcumin on colistin-induced peripheral neurotoxicity using a murine model. Female C57BL/6 mice (n = 10 in each group) were randomly divided into the following: (1) control group (saline), (2) curcumin only group (200 mg/kg/day; orally), (3) colistin only group (18 mg/kg/day; i.p.), (4) colistin (18 mg/kg/day) plus curcumin 50 mg/kg/day group, (5) colistin (18 mg/kg/day) plus curcumin 100 mg/kg/day group, (6) colistin (18 mg/kg/day) plus curcumin 200 mg/kg/day group; all mice were treated for 7 days. Orally applied curcumin was detected in the brain, cerebellum, and sciatic nerve. Co-administration of oral curcumin markedly improved colistin-induced impaired sensory and motor dysfunctions in a dose-dependent manner. Curcumin supplementation at 100 and 200 mg/kg significantly decreased lipid peroxidation and upregulated catalase (CAT) and superoxide dismutase (SOD) activities, ATP levels, and Na+/K+-ATPase activity in sciatic nerve tissue, compared to the colistin alone group. Curcumin supplementation at 200 mg/kg upregulated the levels of AKT, NGF, mTOR, Nrf2, and HO-1 mRNA and concomitantly downregulated Bax, caspases-3, and -9 mRNA; it also decreased caspase-3 and caspase-9 activity. In summary, for the first time, our study reveals that the protective effect of oral curcumin on colistin induced peripheral neurotoxicity is associated with the activation of NGF/Akt and Nrf2/HO-1 pathways and inhibition of oxidative stress. This study highlights the potential clinical application of curcumin as an oral neuroprotective agent coadministered during colistin therapy.
研究领域:
药理学
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神经科学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Xu Zhang,Qian Zhu,Hao Rong,Siyao Zhu,Pan Feng,Jing Li,Yusong Wang,Hong Cheng,Wenbo Liu,Jie Sun,Zhisen Shen,Jilai Li,Yangnan Hu,Renjie Chai
Peripheral nerve injury remains a major clinical challenge due to limited regenerative capacity and insufficient therapeutic strategies. In this study, we developed biomimetic nerve guidance conduits composed of high-concentration gelatin methacryloyl (GelMA) hydrogel (GMH), providing mechanical support and structural integrity. The conduits lumen was filled with a softer, low-concentration GelMA hydrogel (GML) incorporating zeolitic imidazolate framework-8 (ZIF-8) nanoparticles encapsulating nerve growth factor (NGF), enabling sustained neurotrophic delivery. This bilayer design combines mechanical reinforcement with localized biochemical stimulation. In vitro experiments demonstrate that the system can continuously release NGF, exhibits good cellular compatibility, promotes neurite outgrowth in PC-12 cells, and can facilitate the conversion of RAW264.7 cells to an anti-inflammatory phenotype. Rat sciatic nerve injury model experiments have demonstrated that these nerve guidance conduits have a beneficial effect on the regeneration and functional recovery of nerve axons. Together, these findings highlight a versatile platform for nerve guidance conduits with the potential to improve functional recovery in peripheral nerve regeneration.
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Advances
·
2026
·
IF 6.7
Ling Peng,Yusong Pan,Jun Tao,Cuilian Wei,Qianqian Liu,Run Huang,Xiuling Lin,Rui Yue
To address core issues in spinal cord injury repair such as oxidative stress, excessive inflammation and impaired nerve regeneration, this study developed a 3D-printed multifunctional PCP-Res-NGF scaffold. The scaffold achieves stable loading of resveratrol and nerve growth factor by sequentially coating chitosan and polydopamine on the polylactic acid skeleton. Experiments show that the scaffold has pH/ROS dual-responsive drug release characteristics, fitting the S-type Weibull model in simulated injury environments and following a first-order kinetic model under physiological conditions; it exhibits significant scavenging capabilities against DPPH, ·OH, and H 2 O 2 , effectively reducing intracellular ROS levels, an effect attributed to the radical quenching properties of polydopamine and the dual action of resveratrol. By inhibiting the NLRP3 inflammasome, the scaffold shifts lipopolysaccharide-stimulated macrophages from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype, as evidenced by reduced iNOS expression (from 19.62 to 3.43) and increased ARG-1 expression (from 2.06 to 6.04). Furthermore, the scaffold promotes the differentiation of injured PC12 cells into MAP2-positive neurons. In the PCP-Res-NGF (LPS-PR) group, the neurite length reached 119.59 μm, representing a 13.26% increase compared to the LPS-only control group. This scaffold provides a promising therapeutic platform for spinal cord injury repair through synergistic antioxidant, anti-inflammatory and neurodifferentiation-promoting effects.
✓ 已验证
DOI
PubMed
高影响因子
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