Ebrahimkhani Mohammad R, Neiman Jaclyn A Shepard, Raredon Micha Sam B, Hughes David J, Griffith Linda G
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Adv Drug Deliv Rev. 2014 Apr;69-70:132-57. doi: 10.1016/j.addr.2014.02.011. Epub 2014 Mar 5.
Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drives efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models.
肝脏是人体整合代谢和免疫稳态的核心枢纽，也是大多数分子疗法的直接或间接靶点。广泛的治疗和技术需求推动了在体外捕捉肝脏生理和病理生理的努力，从预测小分子药物的代谢和毒性，到理解蛋白质、核酸疗法及靶向疗法的脱靶效应，再到作为药物开发的疾病模型。在此，我们针对基于生物反应器的模型不断演变的格局提供观点，以应对药物发现和开发中的新老挑战，重点强调维持长期肝脏特异性功能方面的设计挑战，以及生物材料和微器件中的新兴技术如何提供新的实验模型。
