Engineering considerations for 3D cell culture and disease modelling on-chip platforms: A review

In the era of miniaturization, the advent of sensors and chips is rapidly increasing for systematic investigation, monitoring and diagnosing unprecedented diseases in preclinical and clinical research. Early-stage detection demands a miniaturized platform/ artificial model in clinical laboratories and healthcare centers. This enables us to investigate and study the physiological processes of the samples and the drug's efficacy on them in a cost-effective and time-efficient manner. The technology of chip systems is rapidly evolving in an attempt to bridge the gaps between preclinical and clinical studies, as well as their wide applications in research laboratories in low-resource settings. Emerging research is focusing on 3D cell culture in microfluidic devices in order to facilitate the uniform distribution of nutrients and in-vitro investigation for assessing various biological processes and phenomena due to limitations in conventional 2D cell culture. It is crucial to understand extensively the significant parameters associated with the development of microfluidic chips for culturing and forming uniform 3D cell masses. The goal of this review is to highlight the various on-chip models that offer precise control over the size of 3D aggregates and their respective microenvironment, making them suitable for drug screening and delivery in therapeutic applications. Additionally, the manuscript discusses the design considerations and feasible microfabrication techniques for generating tumor models, organoids, or organ-on-chips, and the respective computational parameters that govern nutrient flow and permeation, growth conditions, and the microenvironment, cultivating the state-of-the-art microfluidic chips for 3D cell culture.