3D In Vitro Technology for Drug Discovery

3D In Vitro Technology for Drug Discovery
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DOI:
10.2174/157488612800492753
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发表时间:
2012-01-01
影响因子:
1.5
通讯作者:
Hosseinkhani, Hossein
Hosseinkhani, Hossein
中科院分区:
其他
文献类型:
--
作者:
Hosseinkhani, Hossein

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三维(3D)体外系统,可以模拟器官和组织的结构和功能在体内,将是非常有益的各种生物学应用,从基础生物学毒性测试和药物发现。已经有几种尝试来生成3D组织模型,但是这些模型中的大多数需要昂贵的设备,并且其中最严重的缺点是它们离体内成熟的人体器官太远。由于这些问题,药物发现、毒性测试和生物技术工业中的研究和开发是非常昂贵的,并且涉及无数动物的牺牲,并且花费数年时间将单一药物/产品推向市场或发现化学实体的毒性或其他方面。我们的团队一直在积极研究几种替代模型,通过融合生物材料科学,纳米技术和生物学原理来生成3D体外活体器官,称为“人体器官芯片”,以模仿自然器官/组织,以减少动物试验和临床试验。我们已经制造了一种新型的机械和生物学生物模拟胶原基水凝胶,其将提供互连的微孔,其中以类似于具有细胞外基质(ECM)分子的人体器官的方式对人体样品进行3D细胞/器官培养将是可能的。这些产品在不同尺度上模拟天然器官和组织的物理、化学和生物学特性。本文将回顾我们的几个实验的结果,到目前为止,在这个方向和未来的前景。
Three-dimensional (3D) in vitro systems that can mimic organ and tissue structure and function in vivo, will be of great benefit for a variety of biological applications from basic biology to toxicity testing and drug discovery. There have been several attempts to generate 3D tissue models but most of these models require costly equipment, and the most serious disadvantage in them is that they are too far from the mature human organs in vivo. Because of these problems, research and development in drug discovery, toxicity testing and biotech industries are highly expensive, and involve sacrifice of countless animals and it takes several years to bring a single drug/product to the market or to find the toxicity or otherwise of chemical entities. Our group has been actively working on several alternative models by merging biomaterials science, nanotechnology and biological principles to generate 3D in vitro living organs, to be called "Human Organs-on-Chip", to mimic natural organ/tissues, in order to reduce animal testing and clinical trials. We have fabricated a novel type of mechanically and biologically bio-mimicking collagen-based hydrogel that would provide for interconnected mini-wells in which 3D cell/organ culture of human samples in a manner similar to human organs with extracellular matrix (ECM) molecules would be possible. These products mimic the physical, chemical, and biological properties of natural organs and tissues at different scales. This paper will review the outcome of our several experiments so far in this direction and the future perspectives.