Nanyang Technological University, School of Chemical & Biomedical Engineering, Division of Bioengineering, 70 Nanyang Drive, N1.3-B2-13, Singapore 637457, Singapore.
Expert Opin Drug Deliv. 2013 Mar;10(3):369-83. doi: 10.1517/17425247.2013.751096. Epub 2013 Jan 6.
Three-dimensionally (3D) engineered biomimetic tissue models are sought after due to their high fidelity in mimicking various native tissues of the human body, this quality of which gives them an important role at the forefront of drug discovery and development. A multitude of studies have consistently indicated that gene expression profiles, cellular phenotypes, differentiation capabilities and functionalities are all affected by tissue architecture. Thus, the drug evaluation process will stand to gain immense benefits from the fairly accurate predictions of cellular responses displayed by 3D-engineered tissue models when exposed to the drugs of interest in vitro. Stemming from this fact, many studies have set out to capitalize on developing tissue models that are tailored to specific aspects of drug evaluation including the tests of novel drug delivery systems, drug efficacy and toxicity.
The areas covered include fabrication methods and usage of 3D in vitro tumor models in cancer research, focusing on the evaluation of delivery and efficacy of various anticancer drugs or other therapeutic agents. Also covered are the use of 3D in vitro inflammatory tissue models in anti-inflammation research, centering on osteoarthritis (OA) and rheumatoid arthritis (RA) and the use of 3D in vitro tissue models designed for drug toxicity evaluation specifically with liver-mimetic tissues.
Currently available 3D tissue models in various fields of research have already displayed their capabilities in predicting cellular responses to various therapeutic agents and delivery methods with better accuracy than their 2D counterparts, albeit being in need of much refinement before they can be successfully applied for reliable drug evaluation. Given further development and improvement, it is highly probable that the 3D-engineered tissue models may perform as living platforms for dynamic drug evaluation in vitro.
由于能够高度模拟人体各种天然组织,三维(3D)工程仿生组织模型受到广泛关注,这一特性使其在药物发现和开发的前沿领域发挥着重要作用。大量研究一致表明,基因表达谱、细胞表型、分化能力和功能都受到组织架构的影响。因此,药物评价过程将从 3D 工程组织模型在体外接触目标药物时显示出的相当准确的细胞反应预测中获益匪浅。基于这一事实,许多研究都致力于开发针对药物评价特定方面的组织模型,包括新型药物输送系统、药物功效和毒性的测试。
涵盖的领域包括 3D 体外肿瘤模型在癌症研究中的制造方法和用途,重点是评估各种抗癌药物或其他治疗剂的输送和功效。还包括 3D 体外炎症组织模型在抗炎研究中的用途,侧重于骨关节炎(OA)和类风湿性关节炎(RA),以及用于药物毒性评价的 3D 体外组织模型,特别是具有肝样组织的模型。
目前,各种研究领域的现有 3D 组织模型已经显示出能够更准确地预测细胞对各种治疗剂和输送方法的反应,优于其 2D 对应物,但在成功应用于可靠的药物评价之前,还需要进行大量改进。随着进一步的发展和改进,3D 工程组织模型很有可能成为体外动态药物评价的活体平台。