Biofabrication
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2025
·Vol. 17
·期 3
·035029
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IF 8
Xiuxiu Zhang,Zixian Wang,Zeyang Liu,Zhen Zhan,Jianwei Chen,Tao Xu
The 3D hydrogel-based tumor model demonstrates significant potential in replicating the physiological characteristics of in vivo tumor environments for mechanistic studies and drug testing. However, the challenge persists in accurately mimicking a vascularized microtumor with a compartmentalized structure in a controlled, heterogeneous, and high-throughput manner. This study introduces a vascularized 3D tumor model that incorporates an endothelial cell (EC) barrier, created by encapsulating glioma cells and human umbilical vein endothelial cells (HUVECs) within the core (6% gelatin) and shell (10% GelMa) of core–shell microbeads, respectively. Upon culture, the tumor cells develop spheroids within the liquid core, while the HUVECs in the shell migrate and adhere to the GelMa surface, ultimately forming an EC barrier. This 3D microengineered tumor model exhibits angiogenesis in solid tumor spheroids, effectively mirroring the in vivo structure and providing relevant biochemical and biophysical properties. Notably, in comparison to 2D cell cultures, the vascularized tumor model shows significantly higher half-maximal inhibitory concentrations for the anticancer drug doxorubicin. Collectively, these findings highlight the considerable potential of engineered 3D tumor models in drug testing.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2020
·
IF 10.652
Guanglin Zhu,Xuetao Shi,Yingjun Wang
The construction of 3-dimensional (3D) scaffolds with spatially distributed cells throughout remains a challenge despite their high demand for use in tissue and organ repair/regeneration. To tackle this challenge, here we demonstrate a new strategy for building such scaffolds. First, osteoblast-seeded magnetic meshes (consisted of interconnected electrospun magnetic nanoparticles/polycaprolactone composite fibres) were vertically aligned and tightly stacked by a magnetic force. Then, the resultant cell-seeded scaffolds were cultured in medium to facilitate the proliferation of osteoblasts as well as the secretion of extracellular matrix (ECM) by the cells. The type I collagen, main components of secreted ECM, further deposited and filled the interface between the adjacent layers of the meshes, resulting in increased binding between the mesh layers and subsequent successful construction of the 3D scaffold/cell complex with spatially distributed cells throughout the scaffold. Our strategy may pave an all new way to the development of artificial tissues that may take important parts in tissue regeneration and drug testing.
研究领域:
组织工程
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再生医学
·
生物材料
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高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Changcan Li,Gang Xu,Yinhan Wang,Laixin Huang,Feiyan Cai,Long Meng,Bao Jin,Zhuoran Jiang,Hang Sun,Haitao Zhao,Xin Lu,Xingting Sang,Pengyu Huang,Fei Li,Huayu Yang,Yilei Mao,Hairong Zheng
Acoustic holography (AH), a promising approach for cell patterning, emerges as a powerful tool for constructing novel in vitro 3D models that mimic organs and cancers features. However, understanding changes in cell function post-AH remains limited. Furthermore, replicating complex physiological and pathological processes solely with cell lines proves challenging. Here, we employed acoustical holographic lattice to assemble primary hepatocytes directly isolated from mice into a cell cluster matrix to construct a liver-shaped tissue sample. For the first time, we evaluated the liver functions of AH-patterned primary hepatocytes. The patterned model exhibited large numbers of self-assembled spheroids and superior multifarious core hepatocyte functions compared to cells in 2D and traditional 3D culture models. AH offers a robust protocol for long-term in vitro culture of primary cells, underscoring its potential for future applications in disease pathogenesis research, drug testing, and organ replacement therapy.
CAS / MDL:
研究领域:
生物医学工程
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组织工程
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细胞生物学
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药学
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PubMed
高影响因子
Microsystems & Nanoengineering
·
2023
·Vol. 9
·期 1
·1-14
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IF 7.9
Li Shibo,Li Chengpan,Khan Muhammad Imran,Liu Jing,Shi Zhengdi,Gao Dayong,Qiu Bensheng,Ding Weiping
Hepatic sinusoids play a key role in maintaining high activities of liver cells in the hepatic acinus. However, the construction of hepatic sinusoids has always been a challenge for liver chips, especially for large-scale liver microsystems. Herein, we report an approach for the construction of hepatic sinusoids. In this approach, hepatic sinusoids are formed by demolding a self-developed microneedle array from a photocurable cell-loaded matrix in a large-scale liver-acinus-chip microsystem with a designed dual blood supply. Primary sinusoids formed by demolded microneedles and spontaneously self-organized secondary sinusoids can be clearly observed. Benefiting from significantly enhanced interstitial flows by formed hepatic sinusoids, cell viability is witnessed to be considerably high, liver microstructure formation occurs, and hepatocyte metabolism is enhanced. In addition, this study preliminarily demonstrates the effects of the resulting oxygen and glucose gradients on hepatocyte functions and the application of the chip in drug testing. This work paves the way for the biofabrication of fully functionalized large-scale liver bioreactors.
研究领域:
生物医学工程
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组织工程
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微流控技术
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药物发现
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高影响因子
Bioactive Materials
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2024
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IF 18
Jian Wang,Dongyang Zhou,Ruiyang Li,Shihao Sheng,Guangfeng Li,Yue Sun,Peng Wang,Yulin Mo,Han Liu,Xiao Chen,Zhen Geng,Qin Zhang,Yingying Jing,Long Bai,Ke Xu,Jiacan Su
Bone organoids are emerging as powerful tools for studying bone development and related diseases. However, the simplified design of current methods somewhat limits their application potential, as these methods produce single-tissue organoids that fail to replicate the bone microarchitecture or achieve effective mineralization. To address this issue, we propose a three-dimensional (3D) construction strategy for generating mineralized bone structures using bone marrow-derived mesenchymal stem cells (BMSCs). By mixing BMSCs with hydrogel to create a bone matrix-mimicking bioink and employing projection-based light-curing 3D printing technology, we constructed 3D-printed structures, which were then implanted subcutaneously into nude mice, away from the native bone microenvironment. Even without external stimulation, these implants spontaneously formed mineralized bone domains. With long-term culture, these structures gradually matured into fully differentiated bone tissue, completing both mineralization and vascularization. This in vivo bone organoid model offers a novel platform for studying bone development, exploring congenital diseases, testing drugs, and developing therapeutic applications.
研究领域:
组织工程
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再生医学
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干细胞生物学
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骨骼发育
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药物测试
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PubMed
高影响因子
Advanced Fiber Materials
·
2021
·Vol. 3
·期 6
·383-393
·
IF 0
Lei Fan,Liang Minhua,Liu Yang,Huang Hanhao,Li Haofei,Dong Hua
Organ-on-a-chip (OOC) is now becoming a potential alternative to the classical preclinical animal models, which reconstitutes in vitro the basic function of specific human tissues/organs and dynamically simulates physiological or pathological activities in tissue and organ level. Despite of the much progress achieved so far, there is still an urgent need to explore new biomaterials to construct a reliable and efficient tissue–tissue interface and a general fabrication strategy to expand from single-organ OOC to multi-organ OOC in an easy manner. In this paper, we propose a novel strategy to prepare double-compartment organ-on-a-chip (DC-OOC) using electrospun poly( l -lactic acid)/collagen I (PLLA/Col I) nanofiber membrane as tissue–tissue interface. The unique features of PLLA/Col I nanofiber membrane like excellent biocompatibility, strong affinity to multiple cells, adjustable orientation, controllable thickness and porosity endow the tissue–tissue interface with excellent semi-permeability, appropriate mechanical support, inducible cell orientation, good cell adhesion and proliferation. The integration of 3D printing technology during the fabrication process enables precise size control of the tissue–tissue interface and stable bonding with microfluidic channels. More importantly, our fabrication strategy and OOC configuration makes it easy to extend from DC-OOC to multi-compartment organ-on-a-chip (MC-OOC). To show its possible application, in vitro jaundice disease model is established by constructing blood vessel/skin/liver/lung organ-on-a-chip via MC-OOC. The downward trends of the cell viability after perfusion of bilirubin, the variation in cell sensitivity to bilirubin for different type of cells and recovery of cell viability after blue light therapy prove the feasibility of this jaundice disease model. We believe this general strategy of constructing tissue–tissue interface and multi-organ OOC can be used for many other in vitro physiological and pathological models. Graphic Abstract a Schematic illustration on fabrication process of DC-OOC; b construction of blood vessel/skin/liver/lung organ-on-a-chip as in vitro jaundice disease model
研究领域:
生物医学工程
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组织工程
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药物测试
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疾病建模
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