BIOPROCESS AND BIOSYSTEMS ENGINEERING
·
2015
·Vol. 38
·期 12
·2369-2377
·
IF 1.997
Deng Fei,Chen Li,Zhang Ying,Zhao Shan,Wang Yu,Li Na,Li Shen,Guo Xin,Ma Xiaojun
Bioartificial liver (BAL) based on microcapsules has been proposed as a potential treatment for acute liver failure. The bioreactors used in such BAL are usually expected to achieve sufficient flow rate and minimized void volume for effective application. Due to the superiorities in bed pressure drop and operation velocity, magnetically stabilized fluidized beds (MSFBs) show the potential to serve as ideal microcapsule-based bioreactors. In the present study, we attempted to develop a microcapsule-based MSFB bioreactor for bioartificial liver device. Compared to conventional-fluidized bed bioreactors, the bioreactor presented here increased perfusion velocity and decreased void volume significantly. Meanwhile, the mechanical stability as well as the immunoisolation property of magnetite microcapsules were well maintained during the fluidization. Besides, the magnetite microcapsules were found no toxicity to cell survival. Therefore, our study might provide a novel approach for the design of microcapsule-based bioartificial liver bioreactors.
研究领域:
生物工程
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医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2013
·Vol. 102
·期 7
·2408-2416
·
IF 2.834
Li Chen,Ying Zhang,Shen Li,Xiuli Wang,Na Li,Yu Wang,Xin Guo,Shan Zhao,Weiting Yu,Guangwei Sun,Yang Liu,Xiaojun Ma
Immobilization of hepatocytes in microcapsules has been a potentially alternative methodology for bioartificial livers (BALs). Moreover, the stability and permeability are the key parameters of these microcapsules. However, these alginate-based microcapsules are unstable if the surrounding medium disrupts the ionic interactions between alginate and the polycation. As hundreds of components are included in human plasma, the stability and permeability in plasma of microcapsules need to be sufficiently investigated. In the present study, the stability of three kinds of alginate-based microcapsules was evaluated when they were immersed in plasma. Our results showed that stability of alginate-α-poly ( l -lysine)-alginate (α-APA) microcapsules was well maintained, better than those of alginate-ε-poly ( l -lysine)-alginate (ε-APA) and alginate–chitosan–alginate (ACA) microcapsules. Also, factors affecting the stability of microcapsules in plasma were analyzed and it showed that heparin was the key factor that affected the stability of α-APA microcapsules, whereas heparin and low molecular electrolytes such as HCO 3 − and H 2 PO 4 − /HPO 4 2− were the factors to ε-APA and ACA microcapsules. In addition, the permeability evaluation showed no decrease in permeability of microcapsules after incubation in plasma. Our study might provide a foundation for the selection and modification of materials for microcapsule-based BAL devices. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2408–2416, 2014.
研究领域:
生物材料
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组织工程
·
再生医学
·
肝病学
·
药物递送系统
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DOI
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Jiabin Zhang,Xiaodie Chen,Yurong Chai,Yuanyuan Jin,Fenfang Li,Chenya Zhuo,Yanteng Xu,Haixia Wang,Enguo Ju,Yeh-Hsing Lao,Xi Xie,Mingqiang Li,Yu Tao
Acute liver failure (ALF) is a highly lethal condition characterized by massive tissue necrosis, excessive oxidative stress, and serious inflammatory storms, necessitating prompt medical intervention. Although hepatocyte-like cells (HLCs) derived from mesenchymal stromal/stem cells (MSCs) offer a promising alternative cell source for hepatocyte therapy, their low in-vivo integration and differentiation efficiency may compromise the eventual therapeutic efficacy. To this end, MSCs are bioengineered into multicellular spheroids in the present study. The proteomic analyses and experimental results reveal that extracellular vesicles (EVs) derived from these MSC spheroids (SpEV) contain abundant highly expressed bioactive proteins and can be efficiently endocytosed by recipient cells, resulting in enhanced pro-angiogenic and antioxidative effects. In addition, MSC spheroids exhibit superior hepatic cell differentiation compared to an equivalent number of dissociated single MSCs, particularly when being co-cultured with hexagonally patterned endothelial cells in a liver lobule-like arrangement. Following orthotopic implantation in the mouse model, the enhanced paracrine effects of SpEV, combined with an immunoregulatory decellularized extracellular matrix hydrogel carrier and functional artificial liver lobules (ALL), synergically contribute to the effective amelioration of ALF, highlighting the substantial potential for clinical translation.
研究领域:
再生医学
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肝脏疾病
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生物工程
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细胞治疗
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2022
·
IF 2.712
Junjing Zhou,Xinglian Wu,Chaochen Zhao
Hepatocyte scaffold is an essential part in bioartificial liver device. We have designed a novel hepatocyte scaffold based on porcine liver extracellular matrix (ECM) and chitosan (CTS) fabrics. This CTS-ECM scaffold can improve cell adhesion and proliferation. In the present study, an orthogonal test was designed to optimize the CTS/ECM composite scaffold, in which ECM concentration, EDC concentration and EDC to NHS ratio were taken as factors, proportion of nitrogen element and hydroxyproline content as indicators. The cytocompatibility of the novel scaffold for C3A hepatocytes was analyzed in vitro. The orthogonal test demonstrated that the optimal scaffold should be based on ECM concentration of 5 mg/mL, EDC concentration of 5 mg/mL, and EDC to NHS ratio 1:1. C3A hepatocytes cultured on the optimized CTS-ECM scaffolds showed stronger proliferation and functionality than those on Cytodex3 microcarriers (p < 0.05). The CTS/ECM composite scaffold may be widely used as a promising hepatocyte culture carrier, especially in bioartificial liver support systems.
研究领域:
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
Frontiers in Chemistry
·
2022
·
IF 5.545
Liu Yunhong,Peng Xinyan
In artificial liver blood purification system, highly efficient removal of multiple toxic metabolites from whole blood by hemoperfusion still remains a challenge in the clinical field, due to the limited unspecific absorptive capacity and low biocompatibility of adsorbents. In this work, a new pyridinyl-modified hypercrosslinked polystyrene (HCP) adsorbent, named HCP(St-DVB-VP), was constructed directly through a Friedel-Crafts post-crosslinking reaction using a small-molecule crosslinking agent for the first time. The preparation method provides in this study can avert the problem posed by the use of the toxic carcinogenic chloromethyl ether reagent in the traditional HCP resin synthesis process. The results indicated that HCP(St-DVB-VP) had a highly porous structure with a specific surface area of 761 m2 g−1. Notably, the adsorbent demonstrated excellent adsorptive properties towards both protein-bound toxins (bilirubin) and medium- and large-sized molecular toxins (PTH, IL-6) in vitro experiments simultaneously. More importantly, the obtained adsorbent showed acceptable hemocompatibility. Taken together, the low-cost and ecofriendly fabrication method, broad-spectrum adsorption performance and hemocompatibility makes the HCP(St-DVB-VP) promising for whole blood perfusion in artificial liver blood purification in clinical practice.
研究领域:
材料科学
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生物医学工程
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化学工程
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Yilin Wang,Shanshan Wang,Xueqin He,Yupei Li,Tao Xu,Lin Xu,Bo Yang,Xinnian Fan,Weifeng Zhao,Changsheng Zhao
The development of wearable artificial livers was restricted to device miniaturization and bleeding risk with water-soluble anticoagulants. Herein, a double-deck column filled with solid anticoagulant microspheres and Kevlar porous microspheres (KPMs, bilirubin adsorbents) was connected with the principle machine of wearable artificial liver (approximately 9 kg) to treat hyperbilirubinemia beagles for the first time. With the initial normal dose of heparin, the double-deck column could afford 3 h hemoperfusion in whole blood without thrombus formation. The removal efficiency of the double-deck column for total bilirubin (TBIL) was 31.4%. Interestingly, the excessive amounts of hepatocyte metabolites were also decreased by approximately 25%. The “anticoagulant + column” realized safe and effective whole blood hemoperfusion without the plasma separation system and heparin pump; however, the proposed principle machine of wearable artificial liver and “anticoagulant + column” cannot completely replace the bio-liver now. The intelligence of the device and the versatility of the adsorbent need to be improved; moreover, advanced experimental techniques need to be developed to validate the survival rates in animals. Overall, this study is a meaningful trial for the development of wearable artificial livers in the future.
研究领域:
生物医学工程
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肝病学
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药理学
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产品关联
DOI
PubMed
高影响因子
Applied Sciences-Basel
·
2024
·Vol. 14
·期 11
·4537
·
IF 2.5
Yang Li,Yang Zhang,Jianping Gao,Shuguang Liao,Guifeng Zhang
Acute and chronic liver failure are clinically significant conditions, and the artificial liver support system (ALSS) is emerging as a novel and effective approach for the clinical management of liver failure. Within this framework, scaffold materials occupy a pivotal position as integral components of the bioreactor. Elevating the performance capabilities of these scaffolds not only augments the therapeutic efficacy of the artificial liver but also lays the groundwork for refining and selecting large-scale hepatocyte culture models. In this study, we introduced a novel hepatocyte scaffold material designated as PET-COL, crafted by coating polyethylene terephthalate (PET) with collagen. This involved a sequence of modifications, including alkaline hydrolysis, EDC/NHS activation and crosslinking, as well as collagen conjugation. The physicochemical attributes of the scaffold were thoroughly characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), second harmonic generation (SHG), water contact angle measurements, and high-performance liquid chromatography–mass spectrometry (HPLC-MS). Furthermore, an investigation into the material’s biological properties was conducted that encompassed SEM (HepaRG growth), fluorescence staining (assessment of cell viability), staining by trypan blue (HepaRG counting), CCK-8 (proliferation of cells), biochemical testing, and immunosorbent assay. Our findings revealed that collagen was covalently bonded to the PET surface, leading to a substantial enhancement in the material’s hydrophilicity (p< 0.001). The quantity of collagen coating was determined to be precisely 33.30 μg per scaffold. Human liver progenitor HepaRG cells thrived on the PET-COL material. Compared with the untreated group, cell viability, albumin secretion, urea synthesis, and the expression levels of CYP3A4 and CPS1 increased significantly (p< 0.001), demonstrating remarkable biological vitality. The PET-COL scaffold, as developed in this study, holds immense potential for application in bioartificial livers.
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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肝衰竭
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人工器官
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Hongyu Yin,Zhoujun Wang,Xiang Zhang,Weifeng Zhao,Ran Wei,Changsheng Zhao
Chronic liver failure (CLF) and chronic renal failure (CRF) lead to toxins accumulation, severely impairing organ functions. To address this challenge, a Janus polyethersulfone (PES)-based architecture integrated dense membrane with porous monolith is developed, pioneering an approach for simultaneous plasma separation and toxins adsorption. The porous monolith, featuring high porosity about 83.3 % and substantial specific surface area about 102.06 m 2 /g, is prepared using the freezing-induced phase separation (FIPS) technique. The porous monolith is composed of polymer networks of PES and amphiphilic copolymer of poly (vinyl pyrrolidone-co-methyl methacrylate) (VM), as well as activated carbon. Among the various monolith, the PES 18 VM 5 C 2 exhibits the optimal balance of adsorption and anti-protein adhesion. The PES-VM-incorporated dense membrane with a controlled submicron pore size is constructed atop the PES 18 VM 5 C 2 . The dense membrane effectively blocks hemocytes and the porous monolith efficiently adsorbs toxins. Together, the Janus architecture PES 18 VM 5 C 2 @M 16 allows over 85 % of bovine serum albumin (BSA) to permeate, showcasing its selective permeability. After being integrated into a custom 3D-printed supporting device, the PES 18 VM 5 C 2 @M 16 achieves significant clearance in creatinine (67.6 %), uric acid (87.4 %), and bilirubin (89.1 %) during 2-hour plasma adsorption test, with minimal impact on essential plasma components such as total protein, albumin, and cholesterol. This work presents a “Janus Interface Architecture” as next-generation platform for plasma separation and toxins adsorption, offering a promising strategy for wearable artificial liver systems.
研究领域:
生物医学工程
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材料科学
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血液透析
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血浆分离技术
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产品关联
DOI
高影响因子
Science Advances
·
2024
·Vol. 10
·期 23
·
IF 11.7
Bo Deng,Yue Ma,Jialyu Huang,Runbang He,Miaomiao Luo,Lina Mao,Enhua Zhang,Yuanyuan Zhao,Xiaoli Wang,Qiangsong Wang,Mingchang Pang,Yilei Mao,Huayu Yang,Lanxia Liu,Pengyu Huang
The utilization of three-dimensional (3D) bioprinting technology to create a transplantable bioartificial liver emerges as a promising remedy for the scarcity of liver donors. This study outlines our strategy for constructing a 3D-bioprinted liver, using in vitro–expanded primary hepatocytes recognized for their safety and enhanced functional robustness as hepatic cell sources for bioartificial liver construction. In addition, we have developed bioink biomaterials with mechanical and rheological properties, as well as printing capabilities, tailored for 3D bioprinting. Upon heterotopic transplantation into the mesentery of tyrosinemia or 90% hepatectomy mice, our 3D-bioprinted liver effectively restored lost liver functions, consequently extending the life span of mice afflicted with liver injuries. Notably, the inclusion of an artificial blood vessel in our 3D-bioprinted liver allowed for biomolecule exchange with host blood vessels, demonstrating, in principle, the rapid integration of the bioartificial liver into the host vascular system. This model underscores the therapeutic potential of transplantation for the treatment of liver failure diseases.
研究领域:
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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肝病学
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移植学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 3.475
Wei Liu,Mi Zhang,Yan Xiao,Zhaoyang Ye,Yan Zhou,Meidong Lang,Wen-Song Tan
Bioartificial liver (BAL) comprising a functional bioreactor represents a promising treatment, bridging patients with acute liver failure (ALF) to liver transplantation. In this research, a packed-bed (PB) bioreactor by utilizing galactosylated poly(ethylene terephthalate) microfibrous carrier (PET-Gal) was fabricated and evaluated in vitro . Human induced hepatocytes (hiHeps) were dynamically seeded into a PET-Gal loaded bioreactor and cultured for 10 days. During perfusion culture, the effects of bioreactor scaffold on hepatocyte seeding, growth and functionality (albumin secretion and urea production) were determined, compared with that of control with non-modified PET carrier. Afterwards, drug metabolism and detoxification ability of hiHeps were measured. Results demonstrated that the seeding rate and proliferation fold within PET-Gal loaded bioreactor were significantly higher than that of control, resulting in a cell density of (8.17 ± 0.52)×10 7 cells/cm 3 . In contrast to flattened morphology observed in the control, hiHeps cultured in PET-Gal based bioreactor displayed as three-dimensional (3D) cell aggregates with close cell-matrix and cell-cell interactions and high cell viability, leading to higher albumin secretion and urea production. Besides, there were high levels of phase I drug metabolism and ammonia elimination for PET-Gal cultured cells. Therefore, the PET-Gal based PB bioreactor fabricated herein supports high-density hepatocyte growth and meanwhile preserves hepatic functionality, showing great potential in BAL systems application.
研究领域:
生物医学工程
·
组织工程
·
肝病学
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Wei Liu,Mi Zhang,Miaomiao Zhou,Ce Gu,Zhaoyang Ye,Yan Xiao,Yan Zhou,Meidong Lang,Wen-Song Tan
For hepatocyte culture in vitro , the surface feature of utilized scaffolds exerts a direct impact on cell adhesion, growth and differentiated functionality. Herein, to regulate hepatocyte growth and differentiated functionality, modified microfibrous scaffolds were fabricated by surface grafting monoamine terminated lactobionic lactone ( L -NH 2 ) and gelatin onto non-woven poly(ethylene terephthalate) (PET) fibrous substrate (PET-Gal and PET-Gel), respectively. The physicochemical properties of PET scaffolds before and after modification were characterized. Upon 15-day culture, the effects of modified PET scaffolds on growth and differentiated functionality of human induced hepatocytes (hiHeps) were evaluated, compared with that of control without modification. Results demonstrated that both L -NH 2 and gelatin modifications improved scaffold properties including hydrophilicity, water uptake ratio, stiffness and roughness, resulting in efficient cell adhesion, ~20-fold cell expansion and enhanced differentiated functionality. After culture for 15 days, PET-Gal cultured cells formed aggregates, displaying better cell viability and significantly higher differentiated functionality regarding albumin secretion, urea synthesis, phases I (cytochrome P450, CYP1A1/2 and CYP3A4) and II (uridine 5′-diphosphate glucuronosyltransferases, UGT) enzyme activity, biliary excretion and detoxification ability (ammonia elimination and bilirubin conjugation), compared with PET and PET-Gel cultured ones. Hence, as a three-dimensional (3D) microfibrous scaffold, PET-Gal promotes hiHeps growth and differentiated functionality maintenance, which is promisingly utilized in bioartificial liver (BAL) bioreactors.
研究领域:
生物医学工程
·
细胞生物学
·
组织工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Xiang Lin,Jinbo Li,Jinglin Wang,Anne M. Filppula,Hongbo Zhang,Yuanjin Zhao
Bioartificial livers have showcased significant value in the treatment of acute liver failure (ALF). Current efforts are directed toward overcoming challenges in the development of microcarriers, with a specific emphasis on integrating higher-density liver cells to enhance detoxification capabilities. Here, inspired by the radial filtration model in hepatic lobules, ion-specific silk fibroin microcarriers are proposed with biomimetic niches for cultivating functional liver cells at high density. These biomimetic microcarriers are generated by capillary microfluidic device with controllable adjustments of ion type or concentration within the aqueous phase. When cultivating human induced pluripotent stem cell -differentiated mature liver cells on these recrystallized microcarriers, notably enhanced cell proliferation activity, as well as increased metabolic and secretory functionality is observed. Based on these features, the microcarrier-integrated bioreactor can effectively reduce hepatic transaminase levels and significantly improve urea, albumin production, and survival rate in rabbit ALF models is demonstrated. Thus, it is believed that the biomimetic microcarriers and their derived bioreactor may hold potential for clinical applications in managing ALF and other liver diseases.
研究领域:
组织工程
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再生医学
·
生物医学工程
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肝病学
·
干细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）