Abstract

Simple SummaryCancer is one of the diseases with a high mortality rate worldwide. Of the current strategies to study new diagnostic and treating tools, organs-on-chip are quite promising regarding the achievement of more personalized medicine. In this work, 75 out of 820 of the most recent published scientific articles were selected and analyzed through a systematic process. The selected articles present the different microfluidic platforms where cell culture was introduced and was used for the evaluation of cancer treatments efficacy and/or toxicity.The development of cancer models that rectify the simplicity of monolayer or static cell cultures physiologic microenvironment and, at the same time, replicate the human system more accurately than animal models has been a challenge in biomedical research. Organ-on-a-chip (OoC) devices are a solution that has been explored over the last decade. The combination of microfluidics and cell culture allows the design of a dynamic microenvironment suitable for the evaluation of treatments’ efficacy and effects, closer to the response observed in patients. This systematic review sums the studies from the last decade, where OoC with cancer cell cultures were used for drug screening assays. The studies were selected from three databases and analyzed following the research guidelines for systematic reviews proposed by PRISMA. In the selected studies, several types of cancer cells were evaluated, and the majority of treatments tested were standard chemotherapeutic drugs. Some studies reported higher drug resistance of the cultures on the OoC devices than on 2D cultures, which indicates the better resemblance to in vivo conditions of the former. Several studies also included the replication of the microvasculature or the combination of different cell cultures. The presence of vasculature can influence positively or negatively the drug efficacy since it contributes to a greater diffusion of the drug and also oxygen and nutrients. Co-cultures with liver cells contributed to the evaluation of the systemic toxicity of some drugs metabolites. Nevertheless, few studies used patient cells for the drug screening assays.

Highlights

  • The development of new tools for diagnostic and treatment is a process of great importance due to the complexity and variety of diseases that affect the population

  • The different OoC devices were used for model validation, and some contributed to the test of novel treatments such as magnetic microwires [34] and drug-loaded nanocarriers [28]

  • The 3D dynamic cultures provided by the OoC improved some of the features that were lacking in the static culture conditions, such as continuous and well distribute medium supply, waste removal, and oxygen perfusion

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Summary

Introduction

The development of new tools for diagnostic and treatment is a process of great importance due to the complexity and variety of diseases that affect the population. Nanoparticles have shown potential as drug carriers or antibacterial agents, but they have difficulty reaching clinical tests due to the complexity in ascertaining their interaction with specific cellular pathways in specific environments [2]. It is of general agreement in the scientific community that the current models used in the preliminary tests of new diagnostic or treatment techniques do not properly represent the tissue microenvironment found in humans. The research of new in vitro preclinical platforms is being focused on the replication of the in vivo tissue- and organ-level physiological interactions and manifestations of the disease [3,5]

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