The role of matrix compliance on cell responses to drugs and toxins: towards predictive drug screening platforms.

Since the birth of tissue engineering, it has been redefined to include not only the development of tissues for clinical use, but also in vitro models for the study of tissue physiology and pathology. Great strides have been accomplished in the design of in vitro tissue models, yet one area in which they are underrepresented, but where they can have an immediate impact, is the development of platforms for drug screening. By providing more in vivo-like cell environments, such models could address the growing concerns about drug failures due to lack of efficacy or unexpected side effects. This review aims to address the interface between substrate compliance and cell responsiveness to toxins and drugs since compliance has been established as a major determinate of overall cell fate. Here, results from 2D substrates and 3D matrices are discussed. Additionally, examples of biomaterial-based high-throughput stiffness assays in drug screening are presented.