Ranjith Kumar Kankala*, Shi-Bin Wang and Ai-Zheng Chen* Pages 5354 - 5366 ( 13 )
Current preclinical drug evaluation strategies that are explored to predict the pharmacological parameters, as well as toxicological issues, utilize traditional oversimplified cell cultures and animal models. However, these traditional approaches are time-consuming, and cannot reproduce the functions of the complex biological tissue architectures. On the other hand, the obtained data from animal models cannot be precisely extrapolated to humans because it sometimes results in the distinct safe starting doses for clinical trials due to vast differences in their genomes. To address these limitations, the microengineered, biomimetic organ-on-a-chip platforms fabricated using advanced materials that are interconnected using the microfluidic circuits, can stanchly reiterate or mimic the complex tissue-organ level structures including the cellular architecture and physiology, compartmentalization and interconnectivity of human organ platforms. These innovative and cost-effective systems potentially enable the prediction of the responses toward pharmaceutical compounds and remarkable advances in materials and microfluidics technology, which can rapidly progress the drug development process. In this review, we emphasize the integration of microfluidic models with the 3D simulations from tissue engineering to fabricate organ-on-a-chip platforms, which explicitly fulfill the demand of creating the robust models for preclinical testing of drugs. At first, we give a brief overview of the limitations associated with the current drug development pipeline that includes drug screening methods, in vitro molecular assays, cell culture platforms and in vivo models. Further, we discuss various organ-on-a-chip platforms, highlighting their benefits and performance in the preclinical stages. Next, we aim to emphasize their current applications toward pharmaceutical benefits including the drug screening as well as toxicity testing, and advances in personalized precision medicine as well as potential challenges for their commercialization. We finally recapitulate with the lessons learned and the outlook highlighting the future directions for accelerating the clinical translation of delivery systems.
Organ-on-a-chip, tissue engineering, microfluidic platforms, drug delivery systems, personalized precision medicine, microfluidic circuits.
Institute of Biomaterials and Tissue Engineering, Huaqiao University, Xiamen 361021, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian Provincial Key Laboratory of Biochemical Technology (Huaqiao University), Xiamen 361021