Organ-on-chip: Microfluidic approaches for modelling the biophysical microenvironments of diseased tissues

It is well known that over 90% of new drug candidates fail in clinical trials. This is often due to toxicity that has not been predicted in early-stage testing or a lack of drug efficacy in human trial. The lack of successful translation from early discovery to the clinic can be attributed to inadequate pre-clinical models of disease. 2D cell culture, the gold standard, lacks the complexity of in vivo tissues and animal models are inherently genetically, metabolically and immunologically different to humans. This contributes to a lack of predictability in human trial outcomes, costing the sector both time and money when finding new drug candidates for today’s healthcare needs. More recently, a move to 3D cell culture models aims to improve in vitro models of disease, however these models still lack the mechanical and hydraulic environment of in vivo tissues, including the presence of fluid flow, shear stress and mechanical movement.
Organ on Chip is an evolving technology that aims to advance current methods of in vitro disease modelling. These microfluidic platforms allow the integration of fluid flow into 3D cell culture, to emulate the natural movement of fluid through tissues that is critical to cell behaviour but also the distribution and interaction of drugs with diseased tissues. Additionally, the biophysical microenvironment of diseased tissues such as solid tumours are often neglected when developing in vitro models, with current cellular approaches lacking the mechanical rigidity found in tissues. Here, I will present work from our lab on both the mechanical characterisation of in vitro models of pancreatic cancer,1 and also bioengineering organ-on-chip approaches for modelling diseased tissues.2-4
1. Kpeglo, 2022, Matrix Biology Plus, 14, 100109
2. Kpeglo, 2024, Lab on a Chip, 24 (4), 854-868
3. Kpeglo, 2025, Scientific Reports, 24 (4), 854-868
4. Bourn, 2023, Lab on a Chip, 23 (6), 1674-1693