A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy Assays

Abstract

In oncology, the poor success rate of clinical trials is becoming increasingly evident due to the weak predictability of preclinical assays, which either do not recapitulate the complexity of human tissues (i.e., in vitro tests) or reveal species-specific outcomes (i.e., animal testing). Therefore, the development of novel approaches is fundamental for better evaluating novel anti-cancer treatments. Here, a multicompartmental organ-on-chip (OOC) platform was adopted to fluidically connect 3D ovarian cancer tissues to hepatic cellular models and resemble the systemic cisplatin administration for contemporarily investigating drug efficacy and hepatotoxic effects in a physiological context. Computational fluid dynamics was performed to impose capillary-like blood flows and predict cisplatin diffusion. After a cisplatin concentration screening using 2D/3D tissue models, cytotoxicity assays were conducted in the multicompartmental OOC and compared with static co-cultures and dynamic single-organ models. A linear decay of SKOV-3 ovarian cancer and HepG2 liver cell viability was observed with increasing cisplatin concentration. Furthermore, 3D ovarian cancer models showed higher drug resistance than the 2D model in static conditions. Most importantly, when compared to clinical therapy, the experimental approach combining 3D culture, fluid-dynamic conditions, and multi-organ connection displayed the most predictive toxicity and efficacy results, demonstrating that OOC-based approaches are reliable 3Rs alternatives in preclinic.

Fluoropolymer Functionalization of Organ-on-Chip Platform Increases Detection Sensitivity for Cannabinoids

“…We then quantified the CBD absorption in microfluidic channels with surface modification using Teflon AF 2400. We first compared the unmodified microchannels and the microchannels modified with 1% Teflon AF 2400 under static incubations of CBD, as some OOC systems are more suitable for cell culture under static conditions [ 41 ]. Interestingly, we were able to detect a 35-fold increase in the CBD signal from the surface-modified microchannels compared to the bare PDMS channels ( Figure 6 A).…”

An Insight on Microfluidic Organ-on-a-Chip Models for PM2.5-Induced Pulmonary Complications

“…Single organ-on-a-chip has a comparatively simpler design in contrast to multiple organs-on-a-chip. Both fall into the category of microphysiological systems, as they are designed to simulate human physiological conditions and provide insights into the pathophysiology of any disease. , The decision whether to use single or multiple organ-on-a-chip depends on the functional requirements of the physiological processes. The degree of complexity should be kept as low as possible to the minimum required amount to avoid the additional factors that are undesired, which hamper the procedure and can affect the result. , Another approach is to decide which functional tissue to incorporate within the organ on chip, which may include various types such as an engineered tissue, performed organoid, stem cells, etc.…”

“…Both fall into the category of microphysiological systems, as they are designed to simulate human physiological conditions and provide insights into the pathophysiology of any disease. 104 , 117 The decision whether to use single or multiple organ-on-a-chip depends on the functional requirements of the physiological processes. The degree of complexity should be kept as low as possible to the minimum required amount to avoid the additional factors that are undesired, which hamper the procedure and can affect the result.…”