Frontiers in Bioengineering and Biotechnology
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2021
·
IF 5.89
Dong Wenpei,Song Zhicheng,Liu Suihong,Yu Ping,Shen Zhipeng,Yang Jianjun,Yang Dongchao,Hu Qinxi,Zhang Haiguang,Gu Yan
Application of synthetic or biological meshes is the main therapy for the repair and reconstruction of abdominal wall defects, a common disease in surgery. Currently, no ideal materials are available, and there is an urgent need to find appropriate ones to satisfy clinical needs. Electrospun scaffolds have drawn attention in soft tissue reconstruction. In this study, we developed a novel method to fabricate a composite electrospun scaffold using a thermoresponsive hydrogel, poly (N-isopropylacrylamide)-block-poly (ethylene glycol), and a biodegradable polymer, polylactic acid (PLA). This scaffold provided not only a high surface area/volume ratio and a three-dimensional fibrous matrix but also high biocompatibility and sufficient mechanical strength, and could simulate the native extracellular matrix and accelerate cell adhesion and proliferation. Furthermore, rat adipose-derived stem cells (ADSCs) were seeded in the composite electrospun scaffold to enhance the defect repair and regeneration by directionally inducing ADSCs into endothelial cells. In addition, we found early vascularization in the process was regulated by the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. In our study, overexpression of HIF-1α/VEGF in ADSCs using a lentivirus system promoted early vascularization in the electrospun scaffolds. Overall, we expect our composite biomimetic scaffold method will be applicable and useful in abdominal wall defect regeneration and repair in the future.
研究领域:
组织工程
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生物材料
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再生医学
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外科研究
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
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2025
·Vol. 39
·期 16
·e70901
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IF 4.2
Yanping Dai,Xiaoqin Gao
Aging-related decline in male fertility is closely associated with impaired sperm quality and dysregulated autophagy/apoptosis in reproductive tissues. This study elucidates the protective role of the AKT2/mTOR/VEGF axis in mitigating age-induced epididymal dysfunction and sperm deterioration. Utilizing iTRAQ proteomics and transcriptome sequencing in young (6-month) versus aged (18-month) rat models, we identified AKT2 and VEGF as key regulators of reproductive aging. Functional validation revealed that AKT2/mTOR/VEGF activation suppressed oxidative stress, preserved mitochondrial membrane potential, and inhibited autophagy/apoptosis in rat epididymal epithelial cells (REECs, cells lining the epididymis involved in sperm maturation and transport) through downstream targets including Bcl-2, Bax, and LC3-II. Notably, extracellular vesicles (EVs) derived from AKT2-activated REECs enhanced sperm motility and reduced sperm DNA fragmentation through reactive oxygen species (ROS) scavenging and autophagy modulation. Pharmacological inhibition of VEGF or AKT2 exacerbated cellular stress responses, while lentivirus-mediated AKT2 overexpression reversed age-related epididymal damage in vivo. Mechanistically, the pathway crosstalk between mTOR-driven VEGF secretion and EV-mediated intercellular communication emerged as a critical mechanism for maintaining sperm viability. These findings establish AKT2/mTOR/VEGF signaling as a central coordinator of epididymal homeostasis and propose EV-based therapies as promising strategies to counteract male reproductive aging. Graphical The AKT2/mTOR/VEGF axis inhibits oxidative stress in REECs, alleviating autophagy and apoptosis. It promotes sperm activity and motility by secreting EVs, reducing sperm autophagy and apoptosis, and thereby increasing the IVF rate.
研究领域:
生殖生物学
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细胞信号传导
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衰老研究
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分子生物学
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泌尿学
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蛋白质组学
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基因组学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2017
·Vol. 5
·期 33
·6963-6972
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IF 4.543
Qiang Wang,Yanxia Zhang,Bin Li,Liang Chen
The controlled co-release of osteoinductive and angiogenic factors is an efficient approach to promote vascularized bone regeneration, and a suitable controlled release system can largely reduce the usage of these factors to avoid cost and safety problems. In this study, a cell-free vascularized bone tissue engineering system based on a silk fibroin (SF)/nanohydroxyapatite (nHAp) scaffold was developed, in which very low doses of osteoinductive and angiogenic factors, bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), were embedded and released in a controlled manner to facilitate bone formation and vascularization, respectively. BMP-2 and VEGF were adsorbed onto SF microspheres (diameter of 1.5 ± 0.3 μm) that were prepared using a co-flow capillary device, and these microspheres were subsequently incorporated within the SF/nHAp scaffolds to provide controlled release. BMP-2 and VEGF were incorporated into SF microspheres via chemical covalent bonding and physical adsorption, respectively, leading to their controlled and sustained release from the SF/nHAp scaffolds. The rapid initial release of VEGF mimicked its expression at the early bone healing stage and promoted angiogenesis, and the relatively slow and sustained release of BMP-2 facilitated osteogenic differentiation both in vitro and in vivo, and the bone completely bridged the rat calvarial defects after 12 weeks of implantation. Overall, our findings suggest that the controlled dual release of very low doses of BMP-2 (300 ng per scaffold) and VEGF (20 ng per scaffold) from SF/nHAp scaffolds results in a synergistic effect on vascularized bone regeneration; this controlled release system can largely reduce the usage of BMP-2 as compared to other systems.
研究领域:
组织工程
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生物材料
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骨再生
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
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2024
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IF 5.5
Daohuan Lu,Kehan Cai,Zhiwen Zeng,Jun Huang,Nianfang Ma,Botao Gao,Shan Yu
The formation of robust vascular systems within voluminous scaffolds remains a formidable barrier in the realm of tissue engineering. There is a growing interest in the integration of biomaterial scaffolds with multiple physical and chemical stimuli to augment the process of vascularization. This study aims to investigate the combined impact of macroporous structures and vascular endothelial growth factor (VEGF) on cell migration and vascularization. Heparinized hyaluronic acid (HepHA) macroporous hydrogels with differing pore sizes, composed by methacrylated hyaluronic acid (HAMA) and methacrylated heparin (HepMA), were fabricated by a gelatin microspheres (GMS) template leaching method. After characterization of their physical properties, VEGF was immobilized on the HepHA hydrogels. The in vitro release study indicated that the HepHA hydrogels can provide sustained release of VEGF. Subsequently, cells migration of human umbilical vein endothelial (HUVECs) assessment indicated that HUVECs cultured on VEGF-loaded HepHA hydrogels with larger pores (VEGF@HepHA250) migrated the furthest. Finally, the hydrogels were implanted and evaluated using a dorsal subcutaneous model. The histological analyses conducted in vivo were consistent with the in vitro results, VEGF@HepHA250 hydrogels exhibited the most pronounced vascularization four weeks post-implantation, indicating that hydrogels with expanded pores and an enriched VEGF promoted angiogenesis within the hydrogels. This study sheds light on the synergistic effects of VEGF release on 3D cell migration and vascularization within hydrogels of differing pore sizes, thus providing novel insights into the strategic design and fabrication of tissue-engineered scaffolds that are amenable to vascularization.
研究领域:
组织工程
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生物材料
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细胞生物学
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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
ACS Applied Bio Materials
·
2025
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IF 4.7
Zeyu Liu,Yanxin Liu,Tongyu Shi,Kun Fu
Treating large, irregularly shaped bone defects continues to be a major challenge in clinical practice. In this work, an innovative injectable antimicrobial delivery platform is introduced. The therapeutic system leverages the combination of quaternary chitosan salt (QCS) and tannic acid (TA), synergistically supplemented with BMP-2 and VEGF, to enhance the regenerative efficacy. Hydrogen bonding between QCS and TA enhances mechanical strength, while the localized delivery of BMP-2 and VEGF promotes osteogenesis and angiogenesis. The sustained antimicrobial activity of QCS/TA further supports a regenerative microenvironment. Mechanistic analysis showed upregulated osteogenic gene expression in the QCS/TA/BMP-2/VEGF group, consistent with in vivo results─nearly 80% defect closure within 8 weeks. The injectable QCS/TA hydrogel platform incorporated with BMP-2 and VEGF represents a promising strategy for repairing bone defects, emphasizing its pioneering role in addressing clinical challenges.
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
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药物递送系统
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分子生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
·
IF 6.6
Xiaochen Ma,Yubo Cui,Min Zhang,Qinghua Lyu,Jun Zhao
Introduction Oxidant stress, abnormal angiogenesis, and inflammation are three key factors contributing to the development of ocular neovascular diseases (ONDs). This study aims to develop a multifunctional nanodrug, DEX@MPDA-Arg@Si (DMAS), which integrates mesoporous polydopamine, vascular endothelial growth factor (VEGF)-siRNA, and dexamethasone (DEX) to address these therapeutic targets.Methods Physicochemical properties of DMAS were measured using transmission electron microscopy and a nanoparticle size analyzer. The encapsulation efficiency and drug loading capacity of DMAS were measured using a UV-visible spectrophotometer. The in vivo therapeutic efficacy and ocular safety of DMAS were evaluated using three established mouse models, including the alkali burn-induced corneal neovascularization (CoNV) model, the oxygen-induced retinopathy (OIR) model, and the laser-induced choroidal neovascularization (CNV) model.Results The DMAS nanoparticles demonstrated a uniform bowl-like shape with an average size of 264.9 ± 2.5 nm and a zeta potential of −28.2 ± 4.2 mV. They exhibited high drug-loading efficiency (36.04 ± 3.60% for DEX) and excellent biocompatibility. In vitro studies confirmed its potent antioxidant, anti-inflammatory, and anti-apoptotic properties. In vivo, DMAS treatment led to significant therapeutic effects across all models. It effectively inhibited CoNV, promoted corneal repair, and modulated inflammation in the alkali burn model. In the OIR model, DMAS reduced retinal neovascularization by decreasing VEGF expression. In the laser-induced CNV model, it significantly reduced the CNV area and lesion thickness.Conclusion This research developed a multifunctional nanodrug, DMAS, capable of co-delivering VEGF-siRNA and DEX, offering synergistic therapeutic benefits for treating ONDs. The DMAS nanodrug demonstrates promising anti-inflammatory, antioxidative, and anti-angiogenic effects, highlighting its potential as a versatile and effective treatment for multiple ocular conditions.
研究领域:
药学
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纳米技术
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眼科
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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
Meng Zhang,Yumei Wang,Jiayi Wang,Jiayi Zuo,Feng Jiang,Feng Cao
Neovascular ocular diseases are a leading cause of irreversible vision loss. Although intravitreal anti-VEGF therapy is the standard treatment, its invasive delivery and limited efficacy in some patients emphasize the need for non-invasive strategies targeting multiple angiogenic pathways. In this study, we developed a novel hybrid nanoplatform for the non-invasive co-delivery of axitinib (Axi) and telmisartan (Tel) to synergistically inhibit both VEGF and Ang-2 signaling pathways. Poorly soluble drugs were incorporated into layered double hydroxides (LDHs) via a micelle-assisted intercalation strategy and subsequently modified with hyaluronic acid (HA) conjugated to Gly-Val-Sar (GVS), a novel PepT1-targeted tripeptide. The Zn-containing LDH provided controlled drug release, and exhibited anti-inflammatory properties. HA modification prolonged ocular retention, and GVS enhanced transmembrane transport. The resulting Axi/Tel-D@LDH-HA-GVS nanocomposites demonstrated favorable physicochemical properties, efficient uptake by human conjunctival and retinal pigment epithelial cells, and potent inhibition of hypoxia-induced angiogenesis in vitro. In vivo, the formulations exhibited prolonged ocular retention, effective posterior tissue distribution, and good biosafety. In a diabetic retinopathy model, Axi/Tel-D@LDH-HA-GVS nanocomposites restored retinal structure and markedly reduced the expression of VEGF, Ang-2, TNF-α, and IL-6. Collectively, this study provides a promising non-invasive and synergistic strategy for targeted treatment of ocular neovascular diseases.
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PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Yudong Song,Cui Tang,Chunhua Yin
Given that vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), over-expressed in breast cancer cells and M2-like tumor-associated macrophages (M2-TAMs) within tumor microenvironment (TME), work synergistically and independently in mediating tumor progression and immunosuppression, combinatorial immune-based approaches targeting them are expected to be a potent therapeutic modality for patients. Here, polyethylene glycol (PEG) and mannose doubly modified trimethyl chitosan (PEG = MT) along with citraconic anhydride grafted poly (allylamine hydrochloride) (PC)-based nanoparticles (NPs) (PEG = MT/PC NPs) with dual pH-responsiveness were developed to deliver VEGF siRNA (siVEGF)/PIGF siRNA (siPIGF) to both M2-TAMs and breast cancer cells for antitumor immunotherapy. With prolonged blood circulation and intelligent pH-sensitivity, PEG = MT/PC NPs were highly accumulated in tumor tissues and then internalized in M2-TAMs and breast cancer cells via mannose-mediated active targeting and passive targeting, respectively. With the charge-reversal of PC, PEG = MT/PC NPs presented effective endosomal/lysosomal escape and intracellular siRNA release, resulting in efficient gene silencing. Due to the synergism between siVEGF and siPIGF in anti-proliferation of tumor cells and reversal of the TME from pro-oncogenic to anti-tumoral, PEG = MT/PC/siVEGF/siPIGF NPs (PEG = MT/PC/siV-P NPs) exerted robust suppression of breast tumor growth and lung metastasis. This combination strategy may provide a promising alternative for breast cancer therapy.
研究领域:
癌症生物学
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药学
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纳米技术
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免疫疗法
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Xiaolan Ou,Ze Wang,Daojiang Yu,Wenlai Guo,Andrei V. Zvyagin,Quan lin,Wenrui Qu
ABSTRACT Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus (DM), significantly contributing to the risk of amputation and mortality. Reactive oxygen species (ROS) can induce both neurological and structural harm through direct impact and pyroptosis, underscoring the critical role of ROS regulation in mitigating DPN. In this research endeavor, we propose harnessing the inherent antioxidant properties of sulfhydryl groups by grafting them onto gold nanodots through an amidation reaction, resulting in the creation of ROS-responsive AuNDs. Additionally, we aim to synthesize AuNDs-VEGF, wherein VEGF is attached to AuNDs via electrostatic interactions, as a therapeutic strategy for addressing DPN in rat models. The results of in vivo experiments showed that AuNDs and AuNDs-VEGF nanoparticles could increase the nerve conduction velocity, shorten the latency of nerve conduction in the sciatic nerve, promote the regeneration of nerve trophectodermal vessels, improve the structure and function of the sciatic nerve, reduce the apoptosis of neural cells, and alleviate the atrophy of the gastrocnemius muscle. Thus, VEGF-loaded ROS-responsive nanodots present a promising avenue for ameliorating diabetic peripheral neuropathy. This innovative approach not only extends the application possibilities of nanodots but also introduces a novel avenue for the treatment of diabetic neuropathy.
研究领域:
纳米技术
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神经科学
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糖尿病研究
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药学
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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
MICROVASCULAR RESEARCH
·
2021
·
IF 3.514
Yi Wang,Yang Yao,Rong Li,Binghui Wu,Huiqin Lu,Jing Cheng,Zhe Liu,Junhui Du
Introduction Choroidal neovascularization (CNV) is the main pathological change of wet age-related macular degeneration. Anti-VEGF drugs are the most commonly used treatment for CNV. The biggest drawback of anti-VEGF drugs is the recurrence of CNV, which requires repeated therapy several times. Autophagy activation may be involved in reducing the therapeutic effect of anti-VEGF drugs. So, this study aims to elucidate the effect and mechanism of anti-VEGF drugs on endothelial autophagy and neovascularization in vitro. Methods RF/6A cells were randomly divided into five groups: The control group, hypoxia group (1% O 2 , 5% CO 2 , 94% N 2 ), anti-VEGF group (group1: Ranibizumab 100 μg/ml; group2: Aflibercept , 400 μg/ml; group3: Conbercept , 100 μg/ml). Autophagy-related proteins were examined by Western blot . RFP-GFP-LC3 was used to detect autophagy and autophagic flow. Subsequently, we used autophagy inhibitors (3-MA or CQ) to inhibit Conbercept induced autophagy and to observe its effect on angiogenesis in vitro. Proliferation, migration, and tube formation of endothelial cells can be used to study neovascularization in vitro. In this research, the CCK-8 assay was used to detect cell proliferation . Cell migration and tube formation were assessed by wound assay and matrix method, respectively. Flow cytometry and Tunel were used to detect cell apoptosis . Finally, the mechanism of Conbercept activated autophagy was studied. Western blot was used to detect the expression of p53 and DRAM (damage-regulated autophagy modulator), upstream activators of autophagy. Results The protein levels of Beclin-1 and LC3-2/1 in Ranibizumab and Conbercept groups were significantly higher than in the hypoxia group( P < 0.05). While the expression of P62 was decreased ( P < 0.05). The autophagic flux was showed the same results. However, Aflibercept showed the opposite effect on autophagy. Compared with the Conbercept group, autophagy inhibitor 3-MA or CQ can further inhibit cell proliferation and promotes cell apoptosis ( P < 0.05). Conbercept significantly inhibited cell migration compared with the hypoxia group (633.08 ± 72.52 vs. 546.33 ± 24.61), while the autophagy inhibitor group (3-MA or CQ) had a more obvious inhibition effect (309.75 ± 86.36 and 263.33 ± 68.67) ( P < 0.05). For tube formation, the number of tube formation was decreased significantly in the Conbercept group (32.00 ± 2.00) compared to the hypoxia group (39.00 ± 1.53) and even further reduced in 3-MA or CQ group (24.00 ± 3.61, 20.00 ± 2.65). The length of master segments in the hypoxia group was 15,668.00 ± 894.11. It was decreased in Conbercept (13,885.34 ± 730.03). In 3-MA or CQ group, the length of master segments dropped further (11,997.00 ± 433.66, 10,617.67 ± 543.21). Compare with the hypoxia group, the expression P53 and DRAM were increased in the Conbercept group ( P < 0.05). Autophagy-related proteins LC-3, Beclin-1, and DRAM were inhibited by P53 inhibitor Pifithrin-α (PFTα) ( P < 0.05). Conclusion Ranibizumab and Conbercept can trigger the autophagy of vascular endothelial cells while Aflibercept can inhibit it. The combination of Conbercept and autophagy inhibitor can significantly inhibit the formation of angiogenesis in vitro. The mechanism of autophagy activation is related to the activation of the p53/DRAM pathway.
研究领域:
眼科学
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细胞生物学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2021
·
IF 6.291
Jinsong Zhang,Jie Cui,Xinying Li,Xiaohui Hao,Lingli Guo,Hongli Wang,Heliang Liu
Silicosis, a type of lung inflammation and fibrosis caused by long-term inhalation of SiO 2 particles, lacks effective treatment currently. Based on the results of our previous animal experiments, in lungs of SiO 2 -induced silicosis rats, a large number of lymphatic vessels are generated in the early stage of inflammation, which is of great significance for the removal of dust and inflammatory mediators. Here, the molecular mechanism of lymphangiogenesis is further studied. Vascular endothelial growth factor (VEGF-C) is a key pro-lymphangiogenic factor, and its elevated expression is closely related to lymphangiogenesis. In this investigation, we demonstrated that the protein level of VEGF-C was differentially expressed in bronchoalveolar lavage fluid (BALF) and alveolar macrophages (AM) in silicosis patients and healthy controls. We further stimulated human monocyte-macrophage line U937 with SiO 2 , collected the culture supernatants as conditioned medium (CM) for culturing lymphatic endothelial cells (LECs) in vitro, and observed the expression of VEGF-C in the supernatant and its effect on LEC tube formation. The results showed that both CM and single VEGF-C recombinant protein stimulation significantly enhanced LEC proliferation [(1.80 ± 0.18), (1.73 ± 0.16)], chemotaxis [chemotactic cell number (101.40 ± 13.83), (93.40 ± 9.61)], and tube formation [tube number (32.20 ± 7.26), (25.00 ± 6.25); branch number (77.20 ± 6.80), (84.60 ± 7.90)], whereas CM treated with VEGF-CmAb inhibited the proliferation (1.37 ± 0.17), chemotaxis [chemotactic cell number (57.40 ± 8.62)], and tube formation [tube number (7.40 ± 1.85); branch number (47.20 ± 13.44)] of LECs. In addition, CM and VEGF-C can promote the expression of vascular endothelial growth factor receptor 3 (VEGFR-3) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) in LECs, which may further mediate lymphangiogenesis by up-regulating the Src/eNOS downstream signaling molecular pathway. This study is the first to clarify the molecular mechanism of pulmonary lymphangiogenesis in silicosis and may point in the direction of eventual treatments, surveillance, and regulation at a molecular level.
研究领域:
呼吸科
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分子生物学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 11
·1882-1892
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IF 5.047
Chenmin Wang,Yuanman Yu,Han Chen,Shuang Zhang,Jing Wang,Changsheng Liu
Nutrients and oxygen are delivered mainly by blood vessels to nourish the cells and tissues in the body. Thus, biomaterials are processed by loading cytokines, such as vascular endothelial growth factors (VEGF), to facilitate angiogenesis in order to accelerate tissue regeneration. Nevertheless, the unpredictable biosecurity of exogenous cytokines is still a controversial issue for its clinical application. In this study, we constructed a kind of cytokine reservoir utilizing the binding affinity between heparin-like sulfate polysaccharide and endogenous growth factors. Two types of sulfated chitosan hydrogels, namely 6-O-sulfated chitosan (6-O-SCS) and 2-N,6-O-sulfated chitosan (2-N,6-O-SCS) hydrogels, were formed on the surface of the gelatin sponge matrix. The microstructure of the SCS-coated scaffolds is porous and interconnected, which is beneficial for cellular infiltration. Besides, human umbilical vein endothelial cells (HUVECs) can adhere and proliferate well on the surface of the scaffolds. Notably, sulfated chitosan-coated scaffolds exhibit an ability to capture VEGF in vitro & vivo, especially for the 2-N,6-O-SCS-coated scaffold. It is also verified by mice models that sulfated chitosan-coated scaffolds result in a concentrated VEGF microenvironment in specific domains as cytokine reservoirs and induce mass microvessels after implantation into subcutaneous tissues. As such, the sulfated chitosan-coated scaffolds served as VEGF reservoirs to accelerate angiogenesis and wound healing. This beneficial strategy may be applicable to in situ tissue regeneration by capturing more cytokines and promoting healing.
研究领域:
生物材料
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组织工程
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生物医学工程
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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