Biomed Research International
·
2022
·
IF 3.246
Yan Xu,Mingwei Cheng,Peijun Zhu,Shuo Yang,Chunhua Lai,Shulan Xu
During bone tissue regeneration, neovascularization is critical, and the formation of a blood supply network is crucial for bone growth stimulation and remodeling. Previous studies suggest that bioelectric signals facilitate the process of angiogenesis. Owing to their biomimetic electroactivity, piezoelectric membranes have garnered substantial interest in the field of guided bone regeneration. Nevertheless, the knowledge of their influence due to varying surface potentials on the progression of angiogenesis remains ambiguous. Therefore, we proposed the preparation of an electroactive material, P(VDF-TrFE), and investigated its effects on the activity and angiogenic functions of human umbilical vein endothelial cells (HUVECs). The HUVECs were directly cultured on P(VDF-TrFE) membranes with different surface potentials. Subsequently, cell viability, proliferation, migration, tube formation, and expressions of related factors were assessed through appropriate assays. Our results revealed that the negative surface potential groups exerted differential effects on the modulation of angiogenesis in vitro. The P(VDF-TrFE) membranes with negative surface potential exhibited the greatest effect on cellular behaviors, including proliferation, migration, tube formation, and promotion of angiogenesis by releasing key factors such as VEGF-A and CD31. Overall, these results indicated that the surface potential of piezoelectric P(VDF-TrFE) membranes could exert differential effects on angiogenesis in vitro. We present a novel approach for designing bioactive materials for guided bone regeneration.
研究领域:
生物材料
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组织工程
·
再生医学
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细胞生物学
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生物医学工程
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DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Xiang Wu,Fuxiao Wang,Ruiyang Li,Biao Yu,Tianhang Qi,Yunpeng Li,Xiao Chen,Jian Wang,Zhen Geng,Peiran Song,Long Bai,Dongyang Zhou,Hou-Feng Zheng,Qin Zhang,Jiacan Su
Conventional hydrogel drug delivery systems are limited in recapitulating the natural spatiotemporal progression of bone regeneration due to their passive release mechanisms. Here, an enzyme-responsive deoxyribonucleic acid (DNA)-polyethylene glycol (PEG) hydrogel is developed to actively coordinate the sequential processes of angiogenesis, osteogenesis, and mineralization through rational material design. The hydrogel integrates matrix metalloproteinase (MMP)-cleavable peptide-crosslinked PEG networks conjugated with actin-stabilized vascular endothelial growth factor (VEGF)-binding DNA strands, enabling spatiotemporally controlled therapeutic release. Upon implantation, MMPs trigger the hydrogel degradation, releasing VEGF to induce angiogenesis while simultaneously promoting osteogenic differentiation. The actin-stabilized DNA framework maintains structural integrity during this stage, preventing premature phosphate release. Subsequent matrix remodeling liberates nuclease that catalyzes DNA to generate phosphate ions, which synergize with peptides in hydrogels and endogenous calcium to drive mineralization. Molecular dynamics simulations reveal the underlying mechanism of hydrogel-mediated mineralization, demonstrating enhanced calcium phosphate formation. Such temporally controlled cascade significantly improves vascular density, osteogenic marker expression, and mineral deposition compared to controls. This work establishes a bioresponsive platform that dynamically interacts with the biological microenvironment to orchestrate multi-phase bone regeneration, offering new possibilities for complex tissue repair.
研究领域:
生物医学工程
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组织工程
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药物递送系统
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生物材料
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再生医学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Mengtian He,Dayang Xie,Qiannan Cao,Mingxia Jiang,Hongqian Liu,Yingli Yao,Wenming Zheng,Huilin Yuan,Pijun Su,Siting Zhang,Yuxuan He,Shuting Zeng,Yaqing Zeng,Huapan Fang,Hong Wu,Huayu Tian
Retinal neovascularization is one of the most prevalent fundus neovascular diseases, affecting vision and potentially leading to severe complications, such as retinal detachment or irreversible blindness. Current treatments primarily involve intravitreal injections (IVT) of anti-vascular endothelial growth factor (anti-VEGF) agents. However, such treatment often requires repeated injections, develop incomplete responses, and are associated with adverse effects. Therefore, novel therapeutic agents need to be developed that exhibit low side effects and improved therapeutic efficacy of retinal neovascularization. Herein, we develop a novel polymeric gene carrier, phenylboronic acid-modified linear polyethylenimine (LPEI-PBA) that is capable of loading plasmid expressing short hairpin RNA ( p shVEGF), which self-assembles with dexamethasone sodium phosphate (DSP) via electrostatic interactions to form a polymer-based gene-drug co-delivery system ( D SP/L P EI- P BA/ p sh V EGF, DPPV ) for combined neovascularization inhibition. DSP not only exerts anti-inflammatory effects but also enhances the transfection efficiency of LPEI-PBA. DPPV demonstrated favorable anti-neovascular effects both in vitro and in vivo . In an oxygen-induced retinopathy model, a single intravitreal administration of DPPV can significantly inhibited pathological neovascularization, accompanied by the downregulation of glial activation markers glial fibrillary acidic protein (GFAP) and ionized calcium-binding junction molecule 1 (IBA-1), as well as the pro-inflammatory factor interleukin-1β (IL-1β), and the upregulation of the anti-inflammatory factor ARG-1. In conclusion, DPPV nanoparticles effectively inhibit pathological retinal neovascularization through dual anti-inflammation and anti-angiogenesis, showing a promising therapeutic option for fundus neovascularization diseases.
研究领域:
纳米医学
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基因治疗
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眼科学
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药物递送系统
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2020
·
IF 3.644
Zhou Wencheng,Zi Liu,Cen Ying,You Chao,Tian Meng
Skin wound caused by trauma, inflammation, surgery, or burns remains a great challenge worldwide since there is no effective therapy available to improve its clinical outcomes. Herein, we report a copper sulfide nanoparticles-incorporated hyaluronic acid (CuS/HA) injectable hydrogel with enhanced angiogenesis to promote wound healing. The prepared hydrogel could not only be injected to the wound site but also exhibited good photothermal effect, with temperature increasing to 50°C from room temperature after 10 min of near-infrared light irradiation. The cell culture experiments also showed that the hydrogel has no cytotoxicity. In the rat skin wound model, the hydrogel treated wounds exhibited better healing performances. Masson’s trichrome staining suggested that collagen deposition in wounds treated with the hydrogel was significantly higher than other groups. The immunohistochemical staining showed that the hydrogel can effectively upregulate the expression of vascular endothelial growth factor (VEGF) in the wound area at the incipient stage of healing, and the CD 31 immunofluorescence staining confirmed the enhanced angiogenesis of the hydrogel. Taken together, the prepared CuS/HA hydrogel can effectively increase the collagen deposition, upregulate the expression of VEGF, and enhance the angiogenesis, which may contribute to promote wound healing, making it a promising for application in treating skin wound.
研究领域:
生物医学工程
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材料科学
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组织工程
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伤口愈合
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
·
2013
·
IF 3.848
Lin-Hui Zhang,Yong-Liang Jia,Xi-Xi Lin,Hong-Quan Zhang,Xin-Wei Dong,Jun-Ming Zhao,Jian Shen,Hui-Juan Shen,Fen-fen Li,Xiao-Feng Yan,Wei Li,Yu-Qing Zhao,Qiang-Min Xie
Background Ginseng is a traditional Chinese herb that has been used for thousands of years. In the present study, effects and mechanisms of AD-1 were evaluated for its development as a novel anti-lung cancer drug. Methods The cytotoxic activity was evaluated by MTT assay. Flow cytometry was employed to detect cell cycle, apoptosis and ROS. Western blot and immunohistochemistry were used to analyze signaling pathways. Lung cancer xenograft models were established by subcutaneous implantation of A549 or H292 cells into nude mice. Results AD-1 concentration-dependently reduces lung cancer cell viability without affecting normal human lung epithelial cell viability. In A549 and H292 lung cancer cells, AD-1 induces G 0 /G 1 cell cycle arrest, apoptosis and ROS production. The apoptosis can be attenuated by a ROS scavenger — N-acetylcysteine (NAC). In addition, AD-1 up-regulates the expression of p38 and ERK phosphorylation. Addition of a p38 inhibitor SB203580, suppresses the AD-1-induced decrease in cell viability. Furthermore, genetic silencing of p38 attenuates the expression of p38 and decreases the AD-1-induced apoptosis. Treatment with NAC reduces AD-1-induced p38 phosphorylation, which indicates that ROS generation is involved in the AD-1-induced p38 activation. In mice, oral administration of AD-1 (10–40 mg/kg) dose-dependently inhibited the growth of xenograft tumors without affecting body weight and decreases the expression of VEGF, MMP-9 and CD34 in tumor tissue. TUNEL staining confirms that the tumors from AD-1 treated mice exhibit a markedly higher apoptotic index. Conclusions and general significance These data support development of AD-1 as a potential agent for lung cancer therapy.
研究领域:
肿瘤学
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药理学
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细胞生物学
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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 DRUG TARGETING
·
2021
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IF 5.121
Xiangtian Deng,Qingcheng Song,Yiran Zhang,Weijian Liu,Hongzhi Hu,Yingze Zhang
Background Existing therapeutic efficacy of chemotherapy and photodynamic therapy (PDT) is always affected by some resistance factors from tumour environment (TME), such as hypoxia and the antioxidant defense system.Purpose This study aims at developing a cascaded intelligent multifunctional nanoplatforms to modulate the TME resistance for synergistically enhanced chemo- and photodynamic therapies.Methods In this study, we synthesised hollow manganese dioxide nanoparticles (HMDNs) loaded with the hydrophilic chemotherapeutic drug (acriflavine, ACF) and the hydrophobic photosensitizer (chlorine6, Ce6), which was further encapsulated by pH-sensitive liposome to form core-shell nanocomposite, with surface modified with arginine-glycine-aspartic acid (RGD) peptide to achieve tumour targeting.Results After uptake by tumour cells, the liposome shell was rapidly degraded by the low pH, and the inner core could be released from the liposome. Then, the released HMDNs/ACF/Ce6 would be dissociated by low pH and high levels of intracellular GSH within TME to release encapsulated drugs, thereby resulting in synergistic effects of chemotherapy and PDT. Meanwhile, the released ACF could bind with HIF-1a and then inhibit the expression levels of HIF-1’s downstream signalling molecules P-gp and VEGF, which could further strengthen the antitumor effects. As a result, HMDNs/ACF/Ce6@Lipo-RGD NPs with laser irradiation exhibited superior anti-tumour therapeutic efficiency.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Bionic Engineering
·
2021
·Vol. 18
·期 6
·1378-1390
·
IF 2.682
Li Pengfei,Ruan Liming,Wang Ruofan,Liu Tianqi,Song Gao,Gao Xiaofei,Jiang Guohua,Liu Xiaoyan
Nanofibers (NFs) have been widely used in tissue engineering such as wound healing. In this work, the antibacterial ZnO quantum dots (ZnO QDs) have been incorporated into the biocompatible poly (ε-caprolactone)/collagen (PCL/Col) fibrous scaffolds for wound healing. The as-fabricated PCL-Col/ZnO fibrous scaffolds exhibited good swelling, antibacterial activity, and biodegradation behaviors, which were beneficial for the applications as a wound dressing. Moreover, the PCL-Col/ZnO fibrous scaffolds showed excellent cytocompatibility for promoting cell proliferation. The resultant PCL-Col/ZnO fibrous scaffolds containing vascular endothelial growth factor (VEGF) also exhibited promoted wound-healing effect through promoting expression of transforming growth factor-β (TGF-β) and the vascular factor (CD31) in tissues in the early stages of wound healing. This new electrospun fibrous scaffolds with wound-healing promotion and antibacterial property should be convenient for treating wound healing.
研究领域:
组织工程
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伤口愈合
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生物材料
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纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Zhongyuan Zhang,Wenshu Xu,Zhenhua Zhang,Xiaoxue Chen,Hui Jin,Ningning Jiang,Hui Xu
This study was to investigate the potential mechanisms of treatment with metformin (Met) combined with kaempferol (Kae) against postmenopausal osteoporosis. Experiments were conducted in both ovariectomy (OVX)-induced osteoporosis rats and in vitro using RAW264.7 cells, MC3T3-E1 cells, and HUVECs. Results demonstrated the therapeutic effect of Met combined with Kae on osteoporosis. In vivo, Kae alone and in combination with Met treatments enhanced tibial trabecular microstructure, bone mineral density (BMD), and mechanical properties in OVX rats without causing hepatotoxicity and nephrotoxicity. It also reduced bone resorption markers (CTX-1 and TRAP) and increased the bone formation marker (PINP) level in the serum of OVX rats. The expression of bone resorption marker TRAP was reduced, while bone formation markers Runx2 and ALP were enhanced in the bone tissue of OVX rats. Furthermore, Met combined with Kae also promoted the expression of angiogenesis-related markers CD31 and VEGF in OVX rats. In vitro, MC3T3-E1s cells treated with Met combined with Kae showed higher expression of ALP, Runx2, and VEGF. Interestingly, the treatment did not directly promote HUVECs migration and angiogenesis, but enhanced osteoblast-mediated angiogenesis by upregulating VEGF levels. Additionally, Met combined with Kae treatment promoted VEGF secretion in MC3T3-E1, and activated the Notch intracelluar pathway by upregulating HES1 and HEY1 in HUVECs. Meantime, their stimulation on CD31 expression were inhibited by DAPT, a Notch signaling inhibitor. Overall, this study demonstrates the positive effects of Met combined with Kae on osteoporotic rats by promoting osteogenesis-angiogenesis coupling, suggesting their potential application in postmenopausal osteoporosis.
研究领域:
药理学
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骨科
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Zhiqiang Jia,Dini Lin,Chengxuan Tang,Xiaoliang Sun,Lingling Cao,Liangle Liu
Bacterial infection is one of the main causes of delayed wound healing. Hence, the development of antimicrobial dressings with good biocompatibility has high clinical significance and social value. The natural macromolecule, serum albumin, has superior biocompatibility, low immunogenicity, and a good drug-carrying capacity. In this study, human serum albumin (HSA) was modified with methacrylic anhydride to obtain photo-crosslinking properties. Then, the photo-crosslinking HSA was applied to produce homogenized microspheres (HMS) through the nitrogen elution-assisted microfluidic technique and ultraviolet light. Effective loading of vascular endothelial growth factor (VEGF) was achieved by utilizing the adsorption of HSA onto zinc ions and their crosslinking with His-tagged VEGF. The prepared HMS-Zn@VEGF exhibited broad-spectrum antibacterial activity and simultaneously exerted proangiogenic effects in vitro , effectively promoting the healing of infected wounds in rats. In vivo experiments using rats showed that HMS-Zn@VEGF promoted the deposition of collagen around the wound, improved the local inflammatory response, and promoted angiogenesis. In conclusion, our prepared HMS-Zn@VEGF microspheres have good biocompatibility, antimicrobial properties, and angiogenic ability, which can be used for infected wound healing.
研究领域:
生物医学工程
·
药剂学
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伤口愈合
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Minghai Dai,Xiufei Lin,Peng Hua,Simeng Wang,Xiaoliang Sun,Chengxuan Tang,Chi Zhang,Liangle Liu
Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu 2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu 2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.
CAS / MDL:
研究领域:
生物医学工程
·
组织工程
·
材料科学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2019
·
IF 2.121
Huilin Ye,Junjin Zhu,Dan Deng,Shue Jin,Jidong Li,Yi Man
Membranes play pivotal role in guided bone regeneration (GBR) technique for reconstruction alveolar bone. GBR membrane that is able to stimulate both osteogenic and angiogenic differentiation of cells may be more effective in clinic practice. Herein, we fabricated the Sr-doped calcium phosphate/polycaprolactone/chitosan (Sr-CaP/PCL/CS) nanohybrid fibrous membrane by incorporating 20 wt% bioactive Sr-CaP nanoparticles into PCL/CS matrix via one-step electrospinning method, in order to endow the membrane with stimulation of osteogenesis and angiogenesis. The physicochemical properties, mechanical properties, Sr2+ release behavior, and the membrane stimulate bone mesenchymal stem cell (BMSCs) differentiation were evaluated in comparison with PCL/CS and CaP/PCL/CS membranes. The SEM images revealed that the nanocomposite membrane mimicked the extracellular matrix structure. The release curve presented a 28-day long continuous release of Sr2+ and concentration which was certified in an optimal range for positive biological effects at each timepoint. The in vitro cell culture experiments certified that the Sr-CaP/PCL/CS membrane enjoyed excellent biocompatibility and remarkably promoted rat bone mesenchymal stem cell (BMSCs) adhesion and proliferation. In terms of osteogenic differentiation, BMSCs seeded on the Sr-CaP/PCL/CS membrane showed a higher ALP activity level and a better matrix mineralization. What’s more, the synergism of the Sr2+ and CaP from the Sr-CaP/PCL/CS membrane enhanced BMSCs angiogenic differentiation, herein resulting in the largest VEGF secretion amount. Consequently, the Sr-CaP/PCL/CS nanohybrid electrospun membrane has promising applications in GBR.
研究领域:
材料科学
·
生物材料
·
组织工程
·
生物医学工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2014
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IF 5.9
Haiyan Zhu,Chunyan Dong,Haiqing Dong,Tianbin Ren,Xuejun Wen,Jiansheng Su,Yongyong Li
Polylysine with cleavable PEGylation and hydrophobic histidylation (mPEG-SS-Lysn-r-Hism) was designed and developed for efficient siRNA delivery and tumor therapy. mPEG-SS-Lysn-r-Hism was used to carry and deliver small interfering RNA (siRNA) for silencing endogenous vascular endothelial growth factor (VEGF) expression and inhibiting tumor growth in HepG2 tumor-bearing mice. In this gene vector, histidine(Bzl) was selected for hydrophobic histidylation for the proton sponge ability of the imidazole ring and hydrophobic benzyl group. Cleavable PEGylation was introduced for in vivo circulation as well as selective PEG detachment in response to intracellular reduction condition in order to release the genetic payload. PEG detachment induced gene release was supported by agarose gel electrophoresis retardation assay, undertaken in the intracellular relevant reduction condition. In vitro transfection evaluation of histidylated copolymers, using pEGFP as genetic model, indicated significantly higher GFP expression than unmodified counterparts, comparable to the gold standard PEI. The efficacy of hydrophobic histidylation was found to be pronounced in mesenchymal stem cells (MSCs). In vivo application of the VEGF-siRNA package by tailored mPEG-SS-Lysn-r-Hism showed distinct tumor suppression in terms of macroscopic tumor volume and molecular analysis.
研究领域:
药学
·
分子生物学
·
基因治疗
·
癌症研究
✓ 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）