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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Aptamer-Directed Bidirectional Modulation of Vascular Niches for Promoted Regeneration of Segmental Trachea Defect

Runfeng Cao,Zhenying Chen,Qing Ye,Weiyan Sun,Weikang Lin,Hai Tang,Xingseng Yang,Junhao Liang,Yi Chen,Lei Wang,Qingfeng Bai,Ziying Pan,Yulong Hu,Dong Xie,Deping Zhao,Yong Hu,Chang Chen

The simultaneous regeneration of avascular cartilage ring and vascular connective tissue in one biomimetic tracheal substitute has remained a remarkable challenge in the clinical breakthrough of tissue-engineered trachea for repairing segmental trachea defect. Herein, an unprecedented strategy based on bidirectional modulation of vascular niches is developed through tailoring the tissue-specific scaffolds with programmable functional nucleic acids. Namely, the antiangiogenic characteristic of cartilage-specific scaffold enables development of an avascular niche, and thereby facilitating the regeneration of biomimetic cartilage. Conversely, the angiogenic capability of connective tissue-specific scaffold fosters the creation of a vascular niche, and thus enhancing the regeneration of biomimetic connective tissue. Importantly, the steadily immobilized nucleic acids in specific scaffolds enable the seamless integration of angiogenic and antiangiogenic functions without mutual interference. As such, biomimetic tracheas are successfully engineered with the vascular connective tissue scattering between avascular cartilage rings using the assembly of tissue-specific scaffolds. The results from in vivo trachea regeneration and the in situ trachea reconstruction demonstrate the satisfactory tissue-specific regeneration of (a)vascular niches along with optimal structural, mechanical, and physiological features. This study represents the first demonstration of trachea regeneration promoted by modulation of tissue-specific vascular niches, which adds an additional dimension for the clinical trachea reconstruction.

研究领域: 组织工程 · 再生医学 · 生物材料 · 生物医学工程 · 分子生物学
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CHIRALITY · 2019 ·Vol. 31 ·期 4 ·283-292 · IF 1.927

Preparation and characterization of a new open-tubular capillary column for enantioseparation by capillary electrochromatography

Yingjie Li,Yimin Tang,Shili Qin,Xue Li,Qiang Dai,Lidi Gao

In order to use the enantioseparation capability of cationic cyclodextrin and to combine the advantages of capillary electrochromatography (CEC) with open-tubular (OT) column, in this study, a new OT-CEC, coated with cationic cyclodextrin (1-allylimidazolium-β-cyclodextrin [AI-β-CD]) as chiral stationary phase (CSP), was prepared and applied for enantioseparation. Synthesized AI-β-CD was characterized by infrared (IR) spectrometry and mass spectrometry (MS). The preparation conditions for the AI-β-CD-coated column were optimized with the orthogonal experiment design L 9 (3 4 ). The column prepared was characterized by scanning electron microscopy (SEM) and elemental analysis (EA). The results showed that the thickness of stationary phase in the inner surface of the AI-β-CD-coated columns was about 0.2 to 0.5 μm. The AI-β-CD content in stationary phase based on the EA was approximately 2.77 mmol·m −2 . The AI-β-CD-coated columns could separate all 14 chiral compounds (histidine, lysine, arginine, glutamate, aspartic acid, cysteine, serine, valine, isoleucine, phenylalanine, salbutamol, atenolol, ibuprofen, and napropamide) successfully in the study and exhibit excellent reproducibility and stability. We propose that the column, coated with AI-β-CD, has a great potential for enantioseparation in OT-CEC.

CAS / MDL: 15299-99-7
研究领域: 分析化学 · 色谱技术
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JOURNAL OF NANOBIOTECHNOLOGY · 2025 ·Vol. 23 ·期 1 ·1-19 · IF 12.6

Decellularized extracellular matrix-loaded exosome hydrogel for cell-free tracheal scaffold in tracheal defect reconstruction and repair

Shen Zhiming,Shan Yibo,Lu Yi,Zhu Jianwei,Yuan Lei,Chen Wenxuan,Sun Fei,Wang Qi,Wang Yilun,Zhang Yaojing,Xu Xiangyu,Chen Yu,Ge Wei,Chen Wei,Si Panpan,Zhang Renquan,Shi Hongcan

Tracheal reconstruction presents a significant global clinical challenge due to the unique structure and function of the trachea, which complicates its repair. Key challenges include restoring tracheal function post-transplantation, managing surgical complications, and ensuring the long-term survival of transplanted tissue. Furthermore, adequate vascularization of the transplanted trachea, along with the repair of cartilage and epithelial cells, is critical for facilitating functional recovery and successful reconstruction. In this study, a decellularized tracheal matrix was extracted to preserve its natural bioactivity. Nanoclay and GelMA were then employed as carrier materials to integrate with the decellularized tracheal matrix, forming a hydrogel scaffold. Both nanoclay and GelMA offer tunable porous structures and surface properties that promote cell adhesion and proliferation, while providing sufficient mechanical support. By leveraging the biological functions of endothelial progenitor cell-derived exosomes, we successfully loaded exosomes onto the decellularized extracellular matrix, creating a novel cell-free tracheal scaffold for investigating tracheal defect repair. The scaffold exhibited excellent biocompatibility, promoting graft vascularization and facilitating the repair of tracheal cartilage and epithelium. These findings hold significant promise for advancing tracheal reconstruction surgery and offer valuable insights for future research in this area. Graphical abstract

CAS / MDL: 51-79-6 73-78-9
研究领域: 组织工程 · 再生医学 · 生物材料科学
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PHYTOTHERAPY RESEARCH · 2019 ·Vol. 33 ·期 5 ·1579-1591 · IF 3.766

Gambogic acid impairs tumor angiogenesis by targeting YAP/STAT3 signaling axis

Li Wan,Qun Zhang,Sheng Wang,Yong Gao,Xiaofei Chen,Yang Zhao,Xiaoping Qian

Angiogenesis is central to a wide range of physiological and pathological processes including wound healing, macular degeneration, and cancer. Excessive or inappropriate vascular supply of tumors is one of the main targets for cancer therapy. Recently, critical and selective transcriptional factors such as yes-associated protein (YAP) that control the expression of angiogenesis factors have gained increasing attention in antiangiogenic therapy. In this study, we have identified and characterized a novel inhibitor of YAP, gambogic acid (GA), which exerted striking antiangiogenic effects both in vitro and in vivo. We demonstrated that GA remarkably inhibited a variety of vascular endothelial growth factor-induced angiogenesis processes including proliferation, migration, sprouting, and tube formation of endothelial cells in vitro. In addition, GA resulted in decreased neo-vessel formation in Matrigel plugs of mice and chick chorioallantoic membrane. More importantly, we showed that GA limited tumor growth via preventing tumor angiogenesis and vascular maturation. Further mechanistic studies illustrated that GA directly targeted YAP/STAT3 signaling axis, which is critical for the transcriptional regulation of a series of angiogenic factors. Taken together, these preclinical findings suggest that GA significantly repressed tumor angiogenesis and may serve as a promising drug candidate against cancer.

CAS / MDL: 1303-00-0
研究领域: 肿瘤学 · 药理学 · 细胞生物学
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STAR Protocols · 2023 · IF 0

Protocol for fine casting, imaging, and analysis of murine vascular networks with VALID

Jingtan Zhu,Xiaomei Liu,Jianyi Xu,Zhang Liu,Yating Deng,Junyao Dai,Tingting Yu,Dan Zhu

Summary The majority of fluorescent vessel labeling techniques currently available are limited by their expense, incomplete labeling, or complexity. Here, we present VALID ( v essel l a beling via ge l atin-based l i pophilic d ye solution)—a protocol for complete labeling of different vascular networks. We describe steps for preparing different dye hydrogels, murine vascular casting and tissue harvesting, immunolabeling, tissue clearing, and imaging, as well as detailed analysis of the vascular networks. This protocol is helpful for evaluating vascular lesions in studying different vessel-associated diseases. For complete details on the use and execution of this protocol, please refer to Zhu et al. 1

研究领域: 生物学 · 医学成像 · 血管生物学
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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 25 ·4810-4822 · IF 7.571

A novel decellularized trachea preparation method for the rapid construction of a functional tissue engineered trachea to repair tracheal defects

Boyou Zhang,Fei Sun,Yi Lu,Zhihao Wang,Zhiming Shen,Lei Yuan,Qiang Wu,Cong Wu,Hongcan Shi

Long segment trachea defects are repaired by tracheal substitution, while decellularized technology has been effectively employed to prepare tissue engineering trachea (TET). However, its clinical application is restricted by the long preparation cycle, while poor vascularization is associated with the transplantation failure. In the present study, we used sodium lauryl ether sulfate (SLES) to develop a novel rapid decellularized tracheal preparation method, then constructed a TET with revascularization functions. Summarily, we decellularized rabbit trachea using various SLES concentrations. Results from histological analysis, immunohistochemical and DAPI staining, as well as DNA quantitative assay, revealed that 1–0.1% (v/v) SLES treatment not only entirely removed cellular components to reduce its immunogenicity, but also retained the tracheal matrix's gross structure. SEM images, safranine O-fast green staining, total collagen content assay and collagen II immunofluorescence revealed that low SLES concentrations preserved the bioactive components of the decellularized tracheal matrix. Next, we performed cytobiocompatible and cytotoxin assays to verify biocompatibility of the decellularized tracheal matrix, and is confirmed by the omentum transplantation of rats. Results from omentum transplantation revealed that the decellularized tracheal matrix had low immunogenicity and excellent biocompatibility. Its revascularization capacity was confirmed by histologic appearance and CD31 immunofluorescence. Based on these findings, we selected 0.1% (v/v) as the optimal SLES concentration for preparing a decellularized tracheal matrix. Next, we seeded allogeneic bone marrow stem cells (BMSC) onto the matrix to construct TET patches. In vivo tracheal defect reconstruction confirmed the biocompatibility and revascularization capacity of this novel TET, and the formation of a vascular network around the patch promoted submucosa and mucosa regeneration without significant stenosis, 4 weeks post-surgery. In conclusion, we used SLES to successfully develop a novel decellularized approach for the preparation of TET, which has low immunogenic and inflammatory responses, as well as excellent biocompatibility, and revascularization ability in vivo without additional exogenous cytokines.

研究领域: 组织工程 · 再生医学 · 生物医学工程 · 移植学
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MATERIALS & DESIGN · 2021 · IF 7.991

A dual-layer cell-laden tubular scaffold for bile duct regeneration

Jianing Yan,Xixia Liu,Jingyi Liu,Xinjie Zhang,Qiang Zheng,Junjie Nan,Mengjia Lin,Haoqi Pan,Yifan Wang,Xiujun Cai,Jun Yin

Bile duct injury is a common complication of hepatobiliary surgeries in clinical practice with poorly satisfactory treatment outcomes. Implanting a tissue-engineered tubular scaffold for supporting and replacing defected native bile duct is an important treatment option for bile duct injury. Here a dual-layer tubular scaffold with poly (lactic-co-glycolic acid) (PLGA) inner layer and gelatin methacrylate (GelMA)/poly (ethylene glycol) diacrylate (PEGDA) outer layer was fabricated using a two-stage molding method for bile duct regeneration. Further, induced mesenchymal stem cells (MSC)-derived cholangiocyte-like cells were embedded in the outer layer during fabrication. The inner layer of PLGA offered adequate mechanical strength for the scaffold, and the outer layer of GelMA/PEGDA provided excellent biocompatibility and conditions for the MSCs and their induced differentiation. Moreover, cholic acid and its derivates are believed to induce MSC-cholangiocyte differentiation in two-dimensional culture and could affect the MSCs transforming to cholangiocyte-like cells in the hydrogel. Induced-MSC-laden GelMA/PEGDA-PLGA dual-layer tubular scaffold and PLGA single-layer scaffold were transplanted into animal models for assessing the repair effect on bile duct injury. After 12 wk, induced-MSC-laden dual-layer tubular scaffold promoted bile duct repairing and enhanced more intact biliary epithelium regenerating compared to PLGA single-layer scaffold. Therefore, the induced-MSC-laden dual-layer tubular scaffold with superior biocompatibility and distinct function of inducing differentiation exerted a satisfactory effect on bile duct regeneration and could provide an ideal option for the clinical treatment of bile duct injury in the future.

研究领域: 组织工程 · 再生医学 · 生物材料 · 细胞生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Enhancing epithelial regeneration with gelatin methacryloyl hydrogel loaded with extracellular vesicles derived from adipose mesenchymal stem cells for decellularized tracheal patching.

Yi Lu,Yibo Shan,Jianwei Zhu,Zhiming Shen,Wenxuan Chen,Hao Chen,Hongcan Shi

Patch tracheoplasty offers an alternative approach to repairing congenital tracheal stenosis without tension but poses a higher risk of restenosis, granulation tissue formation, and tracheal collapse. The use of tissue-engineered patches for tracheoplasty has been proposed as a solution. Studies suggest that decellularization methods are effective in preparing tracheal patches; however, further research is necessary to improve their efficiency and safety. This study introduces a novel decellularization method using 3-[(3Cholamidopropyl)dimethylammonio]propanesulfonate (CHAPS) and DNase to create a biocompatible tracheal matrix. To enhance the regeneration of epithelial regions within decellularized tracheal scaffolds, this study conducted experimental validations at various levels, both in vivo and in vitro, by introducing extracellular vesicles derived from adipose mesenchymal stem cells as an intervention measure. The ability to promote epithelial regeneration was validated both in vitro and in vivo by incorporating a GelMA hydrogel loaded with adipose-derived mesenchymal stem cell extracellular vesicles (ADMSC-EVs). Evaluation of HBE cell proliferation on tracheal patches treated with varying concentrations of ADMSC-EVs, along with migration and invasion experiments on ADMSC-EV-treated HBE cells, demonstrated enhanced epithelialization in vitro. The inflammatory response and vascular regeneration were assessed via subcutaneous implantation in rats for two weeks. In a rabbit tracheal defect model, the hydrogel loaded with ADMSC-EVs accelerated re-epithelialization in the patch area. This approach shows promise as a novel material for tracheal patching in clinical applications.

CAS / MDL: 111-30-8 9003-98-9
研究领域: 组织工程 · 再生医学 · 干细胞生物学 · 生物医学工程
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BIOMATERIALS · 2017 · IF 8.402

A precision-guided MWNT mediated reawakening the sunk synergy in RAS for anti-angiogenesis lung cancer therapy

Yujie Su,Yahui Hu,Yu Wang,Xiangting Xu,Yang Yuan,Yunman Li,Zeyuan Wang,Kerong Chen,Fangrong Zhang,Xuefang Ding,Min Li,Jianping Zhou,Yuan Liu,Wei Wang

Multi-walled carbon nanotube (MWNT) with its versatility has exhibited tremendous superiority in drug delivery. Despite plenty of researches on MWNT based delivery systems, precision-guided assistances to maximize their profitable properties are still lacking in substantive progress. We developed here a dual-targeting and co-delivery system based on MWNT for antiangiogenesis therapy in lung cancer which aimed at renin-angiotensin system (RAS) dysregulation by synergistically conducting angiotensin II type 1 receptor (AT 1 R) and type 2 receptor (AT 2 R) pathway. In this work, iRGD peptide connected to polyethyleneimine (PEI) was linked to MWNT skeleton, accompanying with candesartan (CD) conjugated to MWNT mediated by cystamine (SS). The functionalized MWNT is assembled with plasmid AT 2 (pAT 2 ) to form iRGD-PEI-MWNT-SS-CD/pAT 2 complexes. iRGD and CD act as pilots for complexes to dually target symbolic ανβ3-integrin and AT 1 R both overexpressed on tumor angiogenic endothelium and lung cancer cell. CD as chemotherapy showed synergistic downregulation of VEGF when combining of pAT 2 and efficiently inhibited angiogenesis . iRGD-PEI-MWNT-SS-CD/pAT 2 complexes greatly appreciated drug activities by changing drug distribution and exhibited remarkable tumor growth suppression in A549 xenograft nude mice . Our work presents that such dual-targeting strategy highly improves the delivery performance of MWNT and open a new avenue for RAS related lung cancer therapy.

研究领域: 肿瘤学 · 纳米医学 · 药理学
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Scientific Reports · 2016 ·Vol. 6 ·期 1 ·1-12 · IF 5.228

Genipin cross-linked decellularized tracheal tubular matrix for tracheal tissue engineering applications

Sun Fei,Jiang Yuan,Xu Yanfei,Shi Hongcan,Zhang Siquan,Liu Xingchen,Pan Shu,Ye Gang,Zhang Weidong,Zhang Fangbiao,Zhong Chonghao

Decellularization techniques have been widely used as an alternative strategy for organ reconstruction. This study investigated the mechanical, pro-angiogenic and in vivo biocompatibility properties of decellularized airway matrices cross-linked with genipin. New Zealand rabbit tracheae were decellularized and cross-linked with genipin, a naturally derived agent. The results demonstrated that, a significant (p < 0.05) increase in the secant modulus was computed for the cross-linked tracheae, compared to the decellularized samples. Angiogenic assays demonstrated that decellularized tracheal scaffolds and cross-linked tracheae treated with 1% genipin induce strong in vivo angiogenic responses (CAM analysis). Seven, 15 and 30 days after implantation, decreased (p < 0.01) inflammatory reactions were observed in the xenograft models for the genipin cross-linked tracheae matrices compared with control tracheae and no increase in the IgM or IgG content was observed in rats. In conclusion, treatment with genipin improves the mechanical properties of decellularized airway matrices without altering the pro-angiogenic properties or eliciting an in vivo inflammatory response.

CAS / MDL: 111-30-8
研究领域: 组织工程 · 生物材料 · 生物医学工程
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COMPOSITES COMMUNICATIONS · 2023 · IF 8

High-performance, thermal management and long-term preservation Epoxy/TPEDA -Fe3O4@ carboxylic carbon nanotube electromagnetic shielding composites

Yunsheng Da,Qiang Liu,Ling Kong,Yiming Du,Xingyou Tian,Yanyan Liu,Hua Wang

In this work, a high-performance electromagnetic interference (EMI) latent curing epoxy composites with combination of modified Fe 3 O 4 and carboxylic carbon nanotube (CNTs) were prepared by magnetic orientation. The unique heterogeneous interface among magnetic nanoparticles and conductive nanowires facilitates the loss of interface polarization, the wave absorbance and the dipole polarization, makes EMI SE T of the material reach respectively 45.86 dB in X-band at the thickness of 2 mm ± 0.1 mm, significantly exceeding that of other epoxy-based shielding materials. In addition, the composites show excellent thermal capacity reaching 1.59 W/m·K. What's more, the oriented epoxy mixture can be preserved at room temperature for 40 days maintaining a low viscosity state without curing, which has a strong practical application prospect in the field of electronic packaging materials.

CAS / MDL: 1760-24-3
研究领域: 材料科学 · 电子工程
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Materials Today Bio · 2023 · IF 8.2

Construction of a novel cell-free tracheal scaffold promoting vascularization for repairing tracheal defects

Zhiming Shen,Fei Sun,Yibo Shan,Yi Lu,Cong Wu,Boyou Zhang,Qiang Wu,Lei Yuan,Jianwei Zhu,Qi Wang,Yilun Wang,Wenxuan Chen,Yaojing Zhang,Wenlong Yang,Yiwei Fan,Hongcan Shi

Functional vascularization is crucial for maintaining the long-term patency of tissue-engineered trachea and repairing defective trachea. Herein, we report the construction and evaluation of a novel cell-free tissue-engineered tracheal scaffold that effectively promotes vascularization of the graft. Our findings demonstrated that exosomes derived from endothelial progenitor cells (EPC-Exos) enhance the proliferation, migration, and tube formation of endothelial cells. Taking advantage of the angiogenic properties of EPC-Exos, we utilized methacrylate gelatin (GelMA) as a carrier for endothelial progenitor cell exosomes and encapsulated them within a 3D-printed polycaprolactone (PCL) scaffold to fabricate a composite tracheal scaffold. The results demonstrated the excellent angiogenic potential of the methacrylate gelatin/vascular endothelial progenitor cell exosome/polycaprolactone tracheal scaffold. Furthermore, in vivo reconstruction of tracheal defects revealed the capacity of this composite tracheal stent to remodel vasculature. In conclusion, we have successfully developed a novel tracheal stent composed of methacrylate gelatin/vascular endothelial progenitor exosome/polycaprolactone, which effectively promotes angiogenesis for tracheal repair, thereby offering significant prospects for clinical and translational medicine.

CAS / MDL: 111-30-8
研究领域: 组织工程 · 生物医学工程 · 再生医学 · 细胞生物学
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