CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Hang Xue,Liangcong Hu,Yuan Xiong,Xiangwei Zhu,Congying Wei,Faqi Cao,Wu Zhou,Yun Sun,Yori Endo,Mengfei Liu,Yi Liu,Jing Liu,Abudula Abududilibaier,Lang Chen,Chenchen Yan,Bobin Mi,Guohui Liu
Hydrogels could be promising wound healing dressings that maintain a moist environment in the wound site and accelerate wound healing. However, the lack of antibacterial effect, suitable mechanical property and adhesiveness limits their applications. Here, we designed a quaternized chitosan-Matrigel-polyacrylamide (QCS-M-PAM) hydrogel with multi-functions. The morphology, swelling ratio, mechanical test, antimicrobial property, hemostatic performance and biocompatibility of the hybrid hydrogel were investigated in vitro and vivo. The hybrid hydrogel showed a three-dimensional (3D) microporous structure, high swelling ratio, excellent stretchable and compressive property, similar modulus to human skin, good adhesiveness, and low cytotoxicity. The results of histology and molecular testing in vivo demonstrated that the hybrid hydrogel could significantly enhance wound healing, collagen deposition, and induce skin adnexal regeneration by upregulating anti-inflammatory factors, and downregulating proinflammatory factors. Together, the present antibacterial hydrogels with hemostatic and adhesive properties are considered to have promising potential used as wound dressings for full-thickness skin defect.
研究领域:
生物材料
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伤口愈合
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组织工程
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生物医学工程
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DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2022
·Vol. 8
·期 1
·e10327
·
IF 10.684
Zi-Yan Xu,Jin-Jian Huang,Ye Liu,Can-Wen Chen,Gui-Wen Qu,Ge-Fei Wang,Yun Zhao,Xiu-Wen Wu,Jian-An Ren
Organoids hold inestimable therapeutic potential in regenerative medicine and are increasingly serving as an in vitro research platform. Still, their expanding applications are critically restricted by the canonical culture matrix and system. Synthesis of a suitable bioink of bioactivity, biosecurity, tunable stiffness, and printability to replace conventional matrices and fabricate customized culture systems remains challenging. Here, we envisaged a novel bioink formulation based on decellularized extracellular matrix (dECM) from porcine small intestinal submucosa for organoids bioprinting, which provides intestinal stem cells (ISCs) with niche-specific ECM content and biomimetic microstructure. Intestinal organoids cultured in the fabricated bioink exhibited robust generation as well as a distinct differentiation pattern and transcriptomic signature. This bioink established a new co-culture system able to study interaction between epithelial homeostasis and submucosal cells and promote organoids maturation after transplantation into the mesentery of immune-deficient NODSCID-gamma (NSG) mice. In summary, the development of such photo-responsive bioink has the potential to replace tumor-derived Matrigel and facilitate the application of organoids in translational medicine and disease modeling.
研究领域:
再生医学
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组织工程
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干细胞生物学
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生物材料科学
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PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2026
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IF 7.8
Liu Han,Sun Ziyan,Jin Yizhou,Li Ruixin,Shan Zhaochen
Salivary gland defects from tumors or trauma are often accompanied by irreversible secretory dysfunction and remain a clinical challenge. Alternative cell sources and suitable scaffolds for salivary gland regeneration remain lacking. A functionalized scaffold system is fabricated by three-dimensional printing combined with freeze-drying to prepare a collagen-silk fibroin-Matrigel scaffold. The scaffold exhibits high porosity and strong water absorption capacity. Its internal surface is coated with a basement membrane extract-rich layer that enhances hydrophilicity and creates a physiologically relevant cell niche. In vitro, a synergistic co-culture system incorporating urine-derived induced pluripotent stem cells (iPSCs), parotid mesenchymal stem cells, and parotid epithelial cells directs the differentiation of iPSCs into KRT18 + /VIM + /AQP5 + iPSC-derived cells. These cells readily adhere to the scaffold, proliferate, and form acinar-like aggregates within its porous architecture. In a rat model of parotid gland trauma, implantation of the scaffold progressively promotes tissue regeneration and attenuates trauma-induced atrophy. Histological analysis reveals that the scaffold recruits host cells to organize within its pores, forming amylase-secreting acinar-like structures. This study provides a reliable seed cell source and a suitable scaffold for structural and functional parotid restoration, offering a potential strategy for salivary gland tissue engineering.
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PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-21
·
IF 17.694
Cao Yuanxiong,Tan Jiayi,Zhao Haoran,Deng Ting,Hu Yunxia,Zeng Junhong,Li Jiawei,Cheng Yifan,Tang Jiyuan,Hu Zhiwei,Hu Keer,Xu Bing,Wang Zitian,Wu Yaojiong,Lobie Peter E.,Ma Shaohua
Transplantation of mesenchymal stem cells (MSCs) holds promise to repair severe traumatic injuries. However, current transplantation practices limit the potential of this technique, either by losing the viable MSCs or reducing the performance of resident MSCs. Herein, we design a “bead-jet” printer, specialized for high-throughput intra-operative formulation and printing of MSCs-laden Matrigel beads. We show that high-density encapsulation of MSCs in Matrigel beads is able to augment MSC function, increasing MSC proliferation, migration, and extracellular vesicle production, compared with low-density bead or high-density bulk encapsulation of the equivalent number of MSCs. We find that the high-density MSCs-laden beads in sparse patterns demonstrate significantly improved therapeutic performance, by regenerating skeletal muscles approaching native-like cell density with reduced fibrosis, and regenerating skin with hair follicle growth and increased dermis thickness. MSC proliferation within 1-week post-transplantation and differentiation at 3 − 4 weeks post-transplantation are suggested to contribute therapy augmentation. We expect this “bead-jet” printing system to strengthen the potential of MSC transplantation.
研究领域:
生物医学工程
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再生医学
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干细胞生物学
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PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2018
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IF 1.911
Mo Li,Ying Wang,Jidi Zhang,Zheng Cao,Shuo Wang,Wei Zheng,Qian Li,Tianqi Zheng,Xiumei Wang,Qunyuan Xu,Zhiguo Chen
A combinatory approach using biomaterials together with cells may improve the efficacy of cell therapy for treatment of various diseases/indications. In the current study, we cultured pyramidal neural precursors (PNPs), neural stem cells (NSCs), and fibroblasts on different materials that included fibrin, collagen, hyaluronic acid (HA), sciatic nerves, and matrigel, to search for the most suitable biomaterial for culture of each cell type. Collagen was fabricated in both an aligned collagen-poly (lactic-co-glycolic acid) (PLGA) composite and an alveolate form; fibrin and hyaluronic acid were made in an aligned form only. Pyramidal neurons have strong projection ability and have potentials in neural circuit reconstruction. However, PNPs showed difficulty in attaching to and growing neurites on most of the materials tested, except for matrigel, in which neurite growth was observed in a three dimentional culture. NSCs and derivatives hold promise in treating neurological diseases. On aligned fibrin, NSCs could differentiate and grow neurites in a directional manner before fibrin was degraded in 2 days. On aligned collagen-PLGA, induced neural stem cells (iNSCs) could survive and differentiate for at least 2 weeks, but the neurites failed to extend in an aligned way. Fibroblast graft are useful in many indications, such as in skin burns. Fibroblasts generally grew better on the tested materials than did the neural cells, and fibroblasts could grow directionally on the aligned fibrin and scattered around on the alveolate collagen. The study provided information which may be used to further optimize the materials to support culture of each type of cells.
研究领域:
神经科学
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再生医学
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细胞生物学
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生物材料学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Yue Fei,Zhichen Ling,Qian Tong,Jun Wang
Purpose Angiogenesis is a tightly controlled process that initiates the formation of new vessels and its dysfunction can lead to life-threatening diseases. Apoptotic extracellular vesicles (ApoEVs) have emerged as a proangiogenic agent with high safety and isolation efficiency profile, and ApoEVs from supernumerary tooth-derived pulp stem cells (SNTSC-ApoEVs) have their unique advantages with an easily accessible parental cell source and non-invasive cell harvesting. However, the detailed characteristics of SNTSC-ApoEVs are largely unknown. This study aimed to investigate the proangiogenic capacity and function molecule of SNTSC-ApoEVs.Methods SNTSC-ApoEVs were isolated and characterized. In vitro effects of SNTSC-ApoEVs on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8, wound healing, transwell, and tube formation assays. The mRNA and protein levels of proangiogenic genes were quantified by qRT-PCR, Western blot, and immunofluorescence analysis. A Matrigel plug model was established in 6-week-old male nu/nu mice for one week, and the in vivo impact of SNTSC-ApoEVs on micro-vessel formation was assessed by histological analysis. Proteomic analysis and RNA sequencing were performed to explore the active ingredients and underlying mechanisms.Results SNTSC-ApoEVs enhanced the proliferation, migration, and angiogenesis of HUVECs in vitro. In the Matrigel plug model in vivo, SNTSC-ApoEVs promoted CD31-positive luminal structure formation. Apart from expressing general ApoEV markers, SNTSC-ApoEVs were enriched with multiple proteins related to extracellular matrix-cell interactions. Mechanistically, SNTSC-ApoEVs transferred COL1A1 to HUVECs and promoted endothelial functions by activating the PI3K/Akt/VEGF cascade.Conclusion SNTSC-ApoEVs can promote angiogenesis by transferring the functional molecule COL1A1 and activating the PI3K/Akt/VEGF pathway, making SNTSC-ApoEVs a promising strategy for the treatment of angiogenesis-related diseases.
研究领域:
干细胞生物学
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血管生成
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分子生物学
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细胞生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Zhiyuan Wang,Renfeng Liu,Youjun Liu,Yuqi Zhao,Yuhao Wang,Botao Lu,Hui Li,Cheng Ju,Weidong Wu,Xinlin Gao,Hailiang Xu,Shixiang Cheng,Yulin Cao,Shuaijun Jia,Chunping Hu,Lei Zhu,Dingjun Hao
Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.
研究领域:
干细胞生物学
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神经科学
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组织工程
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再生医学
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DOI
PubMed
高影响因子
STAR Protocols
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2024
·
IF 1.3
Zitian Wang,Xiaowei Tang,Davit Khutsishvili,Gan Sang,Edgar A. Galan,Jie Wang,Shaohua Ma
Summary In vitro organoids, including cerebral organoids, are usually developed without mechanical compression, which may contribute to a delay in maturation. Here, we present a protocol for encapsulating cerebral organoids with a thin shell of low-concentration alginate hydrogel. We describe steps for organoid generation, microfluidic chip culture, Matrigel coating, expansion culture, and alginate encapsulation. We then detail procedures for maturation culture and organoid characterization. The moderate compressive stimulation that the shell provides promotes cell proliferation and neuronal maturation. For complete details on the use and execution of this protocol, please refer to Tang et al. 1
CAS / MDL:
研究领域:
神经科学
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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
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Yixiong Duan,Yuchuan Jin,Yiyang Jia,Mingyue Zhao,Lang Bai,Shoujun Zhu,Zhentong Wei,Songling Zhang,Bai Yang,Yunfeng Li
Patient-derived tumor organoids (PTOs) closely recapitulate the histopathology, gene expression, and drug response of patient tumor tissues, thereby making them highly reliable in vitro models in preclinical cancer research. Currently, basement membrane extracts (BME or Matrigel) dominate the in vitro culture of PTO models, although BME hydrogels suffer from batch-to-batch variability, possible contamination of murine host cells, and non-tunable mechanical properties. Here, we design and prepare fully synthetic thermoreversible nanofibrillar hydrogels (TNHs) for the growth and enzyme-free release of ovarian PTOs. PTOs cultured in TNHs exhibit morphological, histological, and gene expression similarities to organoids grown in Matrigel and their corresponding tumor tissues. In addition, the on-demand release of PTOs without loss of cell viability and organoid integrity is achieved upon cooling. The released PTOs show a strong tumorigenic ability by xenografts of PTOs in mice. The results show that the fully synthetic TNHs is a highly promising alternative to BME for the establishment of ovarian PTOs in vitro.
研究领域:
癌症研究
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组织工程
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生物材料
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再生医学
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类器官技术
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DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 15
·期 5
·3210-3214
·
IF 1.692
Chen Liu,Chaoyu Mu,Zeng Li,Liang Xu
Overexpression of peptidyl-prolyl cis/trans isomerase, NIMA interacting‑1 (Pin1) is a significant marker of the occurrence and development of tumors. In the present study, the imidazoline ketone herbicide imazamethabenz was investigated as a potential antitumor drug by inhibiting Pin1. Molecular docking and enzyme activity tests verified, for the first time, that the imidazoline ketone compound imazamethabenz effectively inhibited Pin1 in vitro. MTT assays, western blotting, wound healing assay and Matrigel invasion assays revealed that imazamethabenz induced apoptosis and inhibited migration and invasion of the breast cancer cell line MCF‑7, which overexpresses Pin1, by inhibiting the Pin1‑mediated signaling pathway involving vascular endothelial growth factor and matrix metalloproteinase 9. These findings indicated that imazamethabenz offers potential applications for the treatment of tumors as a Pin1 inhibitor.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Weidong Wu,Youjun Liu,Renfeng Liu,Yuhao Wang,Yuqi Zhao,Hui Li,Botao Lu,Cheng Ju,Xinlin Gao,Hailiang Xu,Yulin Cao,Shixiang Cheng,Zhiyuan Wang,Shuaijun Jia,Chunping Hu,Lei Zhu,Dingjun Hao
The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.
研究领域:
神经科学
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干细胞生物学
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组织工程
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再生医学
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疾病建模
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DOI
PubMed
高影响因子
Stem Cell Research & Therapy
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2022
·Vol. 13
·期 1
·1-16
·
IF 8.079
Cui XiaoLing,Wang XiaoTan,Wen Jie,Li Xiao,Li Nan,Hao XuXiao,Zhao BaoXiang,Wu Xunwei,Miao JunYing
Background Human dermal fibroblasts (HDFs) have the potential to differentiate into vascular endothelial cells (VECs), but their differentiation rate is low and the mechanism involved is not clear. The small molecule pathway controls the phenotype of fibroblasts by activating cellular signaling pathways, which is a more convenient method in the differentiation strategy of HDFs into VECs. Methods In this study, HDFs were treated with the different doses of CPP ((E)-4-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl) piperazin-1-yl) styryl)-1-methylpyridin-1-ium iodide), and the mRNA and protein levels of HDFs were detected by qPCR, Western blot, flow cytometry and immunofluorescent staining. The matrigel assays, acetylated-LDL uptake and angiogenesis assays of chick embryo chorioallantoic membrane (CAM) and hindlimb ischemia model of nude mice were performed to evaluate the functions of VECs derived from HDFs. Results Here, we report that the small chemical molecule, CPP, can effectively induce HDFs to differentiate into VECs. First, we observed the morphological changes of HDFS treated with CPP. Flow cytometry, Western blot and qRT-PCR analyses showed that CPP effectively decreased the level of the HDFs-marker Vimentin and increased levels of the VEC-markers CD31, CD133, TEK, ERG, vWF, KDR and CDH5. Detection of the percentage of CD31-positive cells by immunofluorescent staining confirmed that CPP can effectively induce HDFs to differentiate into VECs. The results of Matrigel assays, DiI-ac-LDL uptake, angiogenesis assays on CAM and hindlimb ischemia model of nude mice showed that CPP-induced HDFs have the functions of VECs in vitro and in vivo. Western blot and qRT-PCR analysis showed that CPP induces HDFs to differentiate into VECs by promoting the expression of pro-angiogenic factors (VEGF, FGF-2 and PDGF-BB). Conclusions Our data suggest that the small chemical molecule CPP efficiently induces the differentiation of HDFs into VECs. Simultaneously, this new inducer provides a potential to develop new approaches to restore vascular function for the treatment of ischemic vascular diseases.
研究领域:
细胞生物学
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分子生物学
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血管生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子