Modelling and emulating 3D multi-tissue interactions by microfluidic chip technology
Unit(s) of assessment: General Engineering; Sport and Exercise Sciences, Leisure and Tourism
Research theme: Medical Technologies and Advanced Materials
School: School of Science and Technology
Mice and rats are experimental models widely used in drug development. These, however, exhibit a metabolism and physiology distinctly different to humans and for this reason, do not provide accurate predictions on drug efficacies and safety. This mismatch between species accounts for the 95% attrition rates between pre-clinical and clinical stages of the drug development process. As a result, patients have delayed access to innovative drugs that would allow them better management of musculoskeletal, cardiac and cancer diseases. Microfluidic chips are perfused microdevices that support the culture of relatively complex human cell models under physiological fluid flow shear stress. As these models exhibit human relevance they are postulated to provide more accurate predictions to drug responses than rodents and to accelerate drug discoveries. This project aimed at piloting the fabrication of microfluidic chips depicting unique design features – a resealable lid, and to develop a bone-on-a-chip that mimic the native bone organisation.
Addressing the Challenge
Using 3D printing we successfully piloted the fabrication of chips with multiple designs, materials, and resealable lids. To have a resealable lid is important to allow the insertion of extracellular matrix and cells, however most commercially available microfluid chips lack this feature. We also developed a sequential cell seeding protocol with osteocytes and osteoblasts in a pump-free microfluidic chip OrganoPlate® 3-lane (Mimetas). This protocol enabled the generation of a cell co-culture mimicking the native presentation of bone. Cell viability was consistently maintained as determined by the resazurin (alamar blue) and calcein AM/ethidium homodimer-1 (LIVE/DEAD) assays.
This project was led by Dr Lívia Santos, Prof. Carole Perry, and Dr Yvonne Reinwald and stems from a shared interest in developing healthcare technologies and improving people's lives.
Making a Difference
The bone-on-a-chip has the potential to underpin the development of novel drugs aimed at tackling bone diseases e.g., osteoporosis. This will benefit patients by providing earlier access to innovative drugs and on the other hand animal welfare by enabling the replacement of animals. Findings were presented as a Turbo Talk at the Tissue and Cell Engineering Society and the UK Society for Biomaterials at the University of Nottingham.