In-vitro tumor microenvironment models containing physical and biological barriers for modelling multidrug resistance mechanisms and multidrug delivery strategies.

The complexity and heterogeneity of the three-dimensional (3D) tumor microenvironment have brought challenges to tumor studies and cancer treatment. The complex functions and interactions of cells involved in tumor microenvironment have led to various multidrug resistance (MDR) and raised challenges for cancer treatment. Traditional tumor models are limited in their ability to simulate the resistance mechanisms and not conducive to the discovery of multidrug resistance and delivery processes. New technologies for making 3D tissue models have shown the potential to simulate the 3D tumor microenvironment and identify mechanisms underlying the MDR. This review overviews the main barriers against multidrug delivery in the tumor microenvironment and highlights the advances in microfluidic-based tumor models with the success in simulating several drug delivery barriers. It also presents the progress in modeling various genetic and epigenetic factors involved in regulating the tumor microenvironment as a noticeable insight in 3D microfluidic tumor models for recognizing multidrug resistance and delivery mechanisms. Further correlation between the results obtained from microfluidic drug resistance tumor models and the clinical MDR data would open up avenues to gain insight into the performance of different multidrug delivery treatment strategies.

Controlling Differentiation of Stem Cells for Developing Personalized Organ-on-Chip Platforms.

Organ-on-chip (OOC) platforms have attracted attentions of pharmaceutical companies as powerful tools for screening of existing drugs and development of new drug candidates. OOCs have primarily used human cell lines or primary cells to develop biomimetic tissue models. However, the ability of human stem cells in unlimited self-renewal and differentiation into multiple lineages has made them attractive for OOCs. The microfluidic technology has enabled precise control of stem cell differentiation using soluble factors, biophysical cues, and electromagnetic signals. This study discusses different tissue- and organ-on-chip platforms (i.e., skin, brain, blood-brain barrier, bone marrow, heart, liver, lung, tumor, and vascular), with an emphasis on the critical role of stem cells in the synthesis of complex tissues. This study further recaps the design, fabrication, high-throughput performance, and improved functionality of stem-cell-based OOCs, technical challenges, obstacles against implementing their potential applications, and future perspectives related to different experimental platforms.