A team of chemists, biologists, and engineers is building light-controlled chemical switches that could sculpt living tissue into three-dimensional shapes. The problem is that growing replacement organs or complex tissue models in the lab currently lacks precision—natural signalling molecules called morphogens spread uncontrollably, making it nearly impossible to recreate the intricate patterns found in real tissue. This project aims to solve that by borrowing tools from photopharmacology, a field where drugs are modified with molecular switches that snap on or off when hit with specific wavelengths of light. The researchers will design light-addressable morphogens, build the optical hardware to project 3D light patterns into cell cultures, and test whether they can direct stem cells to form defined structures. If successful, the work would provide proof-of-concept for a fundamentally new way to engineer tissue. Downstream applications could include disease models built from a patient’s own cells, platforms for testing personalised treatments, or eventually synthetic organs. The project is primarily fundamental science—no immediate clinical product—but it opens a route to controlling biological form with the same precision that photopharmacology already brings to individual proteins and cells.
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Tissue engineering is an exciting and rapidly advancing field within biomedical science that holds great promise for revolutionising healthcare. The development of therapeutic approaches to repair, replace, restore, regenerate, and improve tissue and organ function is increasingly important in a society with a rapidly ageing population. Realising the huge potential of tissue engineering necessarily requires the development of new and disruptive methodologies, while overcoming interdisciplinary barriers to enable close collaboration between biologists, chemists, and engineers. The pattern and shape of developing tissue is governed by the dynamic regulation and distribution of soluble biological ligands called morphogens. Recreating such complexity in the context of ex vivo tissue regeneration/engineering presents a significant and unsolved challenge. In theory, controlling and directing tissue development with light represents a major opportunity, due to the high spatial and temporal precision possible when using light as a stimulus. However, light-addressable morphogens, which would be required for the realisation of this approach, are currently unknown. Light-addressable morphogens should be accessible through the burgeoning field of photopharmacology. By combining the principles of pharmacology, photochemistry and optics, photopharmacology enables precise spatiotemporal control over the action of biologically-active agents. The strategic insertion of a light-responsive element (photoswitch) into the structure of a known pharmacological agent allows for a biological activity that can be turned "ON" and "OFF" using light. So far, successful applications in photopharmacology have targeted ion channels, receptors and enzymes, as well as peptides, lipids, and nucleic acids, but the approach has never been applied to the fields of tissue engineering or regenerative medicine. Through a team with expertise spanning physics, engineering, chemistry, biochemistry, molecular, developmental and stem cell biology, this project aims to develop the photopharmacological chemical tools, instrumentation and biological models to demonstrate 3D light patterning of complex tissue. Successful achievement of this aim will provide proof of concept data that can be further developed in order to realise the wider vision of the approach. We expect downstream applications of the approaches pioneered in this project to have transformational and disruptive impact. For example, using light-patterning to recreate complex 2D and 3D architectures of healthy or dysfunctional cells will allow for the generation of models to study diseases, models to investigate personalised medicine, models for further developmental biology studies, or the creation of synthetic organs.
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