2021 FRAME Innovation Grant winner Dr Roger Domingo-Roca from the University of Strathclyde was awarded £8,133.48 to help explore the development of a 3D tumour model which incoporates the flow of nutrients the tumour cell would experience in the body.

The problem

Cancer research commonly uses animals to understand disease progression. Animal models, however, often fail to provide the detailed insight into human conditions that we need to develop treatments for those affected.

But there are scientists working on alternatives. A recent focus has been on developing human based models that mimic human tissues and can replicate real life physiological environments. Creating these ‘microphysiological systems’ requires well-characterised tissue-mimicking materials which also faithfully replicate the complexity of the tiny blood vessels that develop within and around tumours.

To complicate matters, soft tissues are very complex structures, and their properties can change depending on multiple factors. For example, how they are compressed or stretched when we move can affect their acoustic properties, and therefore how they respond to ultrasound. And ultrasounds are vital for accurate diagnosis and monitoring of cancers.

Methods like organs-on-chips (also referred to as ‘microphysiological systems’), are advancing our ability to replicate the function of the desired organ or tissue, but they’re still relatively simple. For example they still lack the complexity of the microvasculature, which is fundamental in tumour growth and in other diseases. The successful development of both healthy and diseased tissue-mimicking materials is critical for the future of animal free medical research.

The project

Roger Domingo-Roca at the University of Strathclyde, is working with his team to lay the groundwork in developing a 3D model of solid tumours that mimic their natural intricate structure, right down to the network of micro-blood vessels being grown to supply the tumour’s interior with oxygen and nutrients.

Roger’s vision is to replicate the complexity of the tumour and its microvasculature in 3D, potentially based on real patient scans, thereby creating a human-relevant non-animal model.

Since winning a FRAME Innovation Grant in 2021, Roger and his team have tested a series of different hydrogels, looking at their morphological, mechanical and acoustic properties, and cellular compatibility.

The first step was to determine whether the hydrogels supported independent 3D printing of 3D entangled networks, which they then tested by perfusing different coloured dyes through them. They’ve since successfully managed to reproduce the microvasculature of real tissue using the different hydrogels in a single 3D-printed model.

The next step was to see if this 3D structure supports the growth of human cells, both on, and within it. This ‘biocompatibility’ testing was done by culturing human umbilical vein endothelial cells in the laboratory. Using fluorescence microscopy, the team have analysed the behaviour of these cells on all the hydrogels that they developed. They discovered that each material influences cellular morphology and function and have identified which provide the most realistic ‘response’ giving similar cell count and morphology to traditional cell culture approaches using tissue culture plastics. They’ve shown that human umbilical vein endothelial cells have the ability to adapt to curved surfaces (inside 3D-printed channels and on plated gels with a meniscus), which gives them huge potential for developing lab-based vascular endothelial systems.

The potential

Reproducing the complex structures of soft tissues must include their dynamic mechanical behaviour, as they stretch, compress or bend with our body movement and position. Roger’s approach aims to narrow the gap between current organ-on-chips and real life tissue microenvironments, replacing animal tissues in models for experimental medicine.