Organ-on-chip models: new opportunities for biomedical research

Animal models are frequently used in biomedical research. However, recently a controversial debate about the transferability of data obtained in mouse models to human conditions emerged. Although cell-based in vitro approaches can be an alternative, conventional cell culture methods hardly reflect cellular cross-communication and neglect essential physiological parameters. Biochipembedded tissue culture allows an optimal supply with nutrients and oxygen, an efficient removal of catabolic metabolites, and enables a physiological cell polarization and communication within tissues creating a complex physiological microenvironment in vitro. The combination of animal as well as human organ-on-chip with reliable in vivo models will create new possibilities for an integrative research strategy covering analysis from the cellular mechanistic level in vitro to the phenotype level in vivo. Standard 2D cell culture still represents the most widely used technique to study cellular behavior, for example, in response to altered signaling pathways or treatment with pharmacological substances. However, its relative ease of use frequently is accompanied by severe limitations. Enrichment of waste products, limited supply with nutrients restricted by slow diffusion or lack of cell type-specific mechanostimulatory forces often result in rapid dedifferentiation of cells under these nonphysiological conditions. Novel microfluidically perfused organ-on-chip technologies represent innovative alternatives to circumvent these problems, allowing the establishment of organ models mimicking the 3D arrangements of cell types and cell layers close to physiological conditions [1]. Recently developed organ-on-chip systems are composed of multiple organ-specific cell types that are arranged in a bioinspired fashion resembling key features of organ-specific morphology. Although the research field of organ-on-chip models is still in its infancy, some of these models are already capable of closely reflecting in vivo cell–cell communication thereby creating an endogenous microenvironment that resembles key issues of organ physiology with defined organ-specific functions in vitro. Bhatia and Ingber [2] recently defined organs-on-chip as “...microOrgan-on-chip models: new opportunities for biomedical research