THE PROTECTIVE ONE
VISUAL ART
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SCIENCE
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TECHNOLOGY
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ENGINEERING
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VISUAL ART - SCIENCE - TECHNOLOGY - ENGINEERING -
by Georgios Ziakas
‘The Protective One’, by Georgios Ziakas, depicts chondrocytes, the cells found in healthy cartilage protecting our joints and bones throughout our bodies. A closer look into this vivacious piece helps to identify individual circles, pulsing with iridescence, that exist in a softer web of nets, connecting it all together. This piece has a striking resemblance to Yayoi Kusama’s ‘Infinity Mirrored Room – The Souls of Millions of Light Years Away’, where each illuminated lightbulb is said to represent a human soul from millions of light years away.
Georgios is a materials scientist with a keen interest in the use of cutting-edge technologies that merge principles of tissue engineering and biomaterials to mimic real life experimental conditions, enabling research without the use of laboratory animals. He is now a PhD researcher at Queen Mary University London (QMUL), investigating the use of these technologies to further understand cartilage mechanobiology.
“I was thrilled as my first thought was: so, this is what arthritis looks like! Now let’s see how we can make it better.”
A description from Georgios:
Inflammation in cartilage plays a critical role in the progression of various joint diseases, like osteoarthritis or rheumatoid arthritis. At the same time, cartilage is constantly exposed to mechanical forces, a key factor influencing chondrocyte behaviour and effectively modulating inflammatory responses within these cells. Apart from modulating cellular behaviour, mechanics were shown to alter drug response in vitro, expanding our understanding of the high rate of drug failure seen in preclinical trials.
My research focuses on investigating how different mechanical regimes regulate inflammatory pathways, essential for developing effective therapeutic strategies.
“Our ultimate goal is not only to further our understanding of chondrocyte responses in 3D organ chip systems but also to improve the predictability of preclinical drug testing.”
To achieve this, I utilise commercial organ-chip platforms that enable the application of mechanical forces directly on cultured cells in a controlled environment, thereby providing more physiologically relevant models.
This technology, combined with Super-Resolution Spinning Disk Confocal microscopy, allows for precise spatial characterisation of the interplay between inflammation and various mechanical strain regimes. Our ultimate goal is not only to further our understanding of chondrocyte responses in 3D organ chip systems but also to improve the predictability of preclinical drug testing. Many thanks to the Centre for Predictive In vitro Models at QMUL and the Knight Lab for making all this work happen and for their support in every step.
A deeper dive into inflammation in the context of Georgios’s research:
Inflammation is the body's response to harmful stimuli, with acute inflammation being the rapid response to injury or infection and chronic inflammation leading to conditions like osteoarthritis through prolonged and ongoing tissue damage.
For those with healthy joints, exercise has been shown to affect inflammatory responses; intensive exercise might induce acute inflammation, which is temporary and aids in tissue repair, whereas chronic inflammation from continuous strain can damage cartilage and contribute to joint diseases. On the other hand, when joints are not so healthy and tissues are already inflamed, it is unclear on the exact effects of exercise, because the mechanism is heavily dependent on duration, frequency and intensity of exercise, in addition to the primary cause of inflammation.
Georgios studies the inflammatory response of chondrocytes under existing conditions of inflammation, and the influence of mechanical strain. To do this, he images the translocation of the p65 protein from the cytoplasm of chondrocytes to their nucleus (labelled in red in the image) - a step in the NF-κB pathway, one of the major inflammatory signalling pathways, that typically occurs when cells are under stress.
He also investigates whether this process is then reverted when mechanical stimuli are applied, measuring the secretion of Nitric Oxide (labelled in green in the image) - also highly produced when cell are under stress.
A deeper dive into organ-chips in the context of Georgios’s research:
To induce the mechanical stimuli, Georgios uses an organ-chip, a microfluidic device that contains engineered miniature tissues grown inside. He uses a system that applies fluid shear stress and tissue strain to replicate the mechanical environment of human organs. This includes the spatial variation of applied strain under which our tissues and joints are for the most of our life and especially during intense movement.
“The next step would be to apply this knowledge to personalised organ-chips using patient derived cells. ”
Fluid shear stress has already shown its translational value to examine the therapeutic efficacy of chloroquine for Covid-19. While chloroquine was shown to be efficacious in cell culture experiments, it was found to be ineffective in an organ chip with mechanics applied and subsequently also in patients.
This highlights the need of incorporating biomechanics in organ-chips as traditional models often fail to predict human responses accurately, leading to high rates of drug failure in clinical trials. Georgios says that the next step would be to apply this knowledge to personalised organ-chips using patient derived cells. Despite the evident advantages, these new techniques are associated with disadvantages including lower throughput and higher complexity and cost.
What does the title of your piece signify?
The “Protective One” is a reference to the protective role of chondrocytes, acting as a shield for our joints and bones against the harsh conditions that we put them through each day.
How did it make you feel seeing this image whilst you were doing your research?
I was thrilled as my first thought was: so, this is what arthritis looks like! Now let’s see how we can make it better.
Welcome GEORGIOS!
I really enjoy communicating science and especially discussing the exciting possibilities new technologies offer for our future. I have a passion for nice images (especially fluorescent) and saw that you have already published some impressive ones!
