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German and Swiss research teams have combined their respective skills to develop a synthetic tissue mimic which, like living tissue, can self-protect against environmental threats. When the environment becomes more acidic, the “artificial cells” forming the synthetic tissue offer collective homeostatic protection by self-regulating acidity inside and out. These self-protecting tissue mimics could come to the rescue of our immune system, opening up new perspectives in cancer therapy.

The results of the study, led by Joshua Krehan, were published in Chem in February 2025.

Most tumours acidify their environment and, in so doing, silence the immune system. Imagine if we could enable the immune system to attack using synthetic tissues which, in the vicinity of the tumour, would raise the pH to the desired level. This may soon be possible thanks to recent work by Andreas Walther’s group on the engineering of synthetic tissues.

“Communicating materials are the future of therapies”

For more than a decade, Andreas Walther‘s group at Johannes Gutenberg University Mainz, Germany, has been focusing on the development of life-like materials and systems, from the nanometric to the macroscopic scale, with chemical intelligence.

“Chemically intelligent systems are more than just responsive systems. They can process and store information and adopt a specific response adapted to a change,” said Andreas.

Andreas is also the leader of COM2life, an initiative that aims to create intelligent synthetic materials capable of interacting and communicating with living systems. “I believe that communicating materials are the future of therapies.”

Combining expertise in pH feedback systems and microfluidics to produce homeostatic “artificial cells”

Recently, Walther’s group collaborated with Esther Amstad’s group at the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland. Combining their respective expertise in pH feedback systems and microfluidics, they have designed cell-sized capsules, which they call artificial cells (ACs), with homeostatic, i.e. self-regulating, properties.

ACs have reversible permeability, one category being permeable in an acidic environment and the other in a basic environment, and both contain certain enzymes which, in the presence of the appropriate fuel, produce a chemical reaction that modifies the pH.

“Under normal conditions, nothing happens, the pores of the ACs are closed and the fuel from the environment cannot come into contact with the enzyme,” explained Andreas.

But under external threats, with the environment suddenly becoming acidic or basic, the ACs open their pores and potentially leak a cargo.“For normal capsules, this would be the end, but in our system the enzyme inside processes the fuel and changes the pH, thereby closing the pores of the ACs via a chemo-structural feedback mechanism. The system homeostatically self-regulates its internal state and that of the environment, and it can do so multiple times,” Andreas added.

From homeostatic artificial cells to self-protecting prototissues

After working on individual artificial cells, the researchers prepared artificial spheroids (tissues composed of a single type of cell). They showed that their tissue system presented collective behaviour, similar to the circle defence strategy of the musk ox, a large mammal living in the Arctic.

“When musk oxen are threatened by predators, they form a circle of adults around the young calves, which remain in the centre. We observed a similar reaction of our prototissue when faced with external threats. If they hadn’t been in a tissue, all the ACs would have reacted and lost their contents. Here, only the outermost cells reacted to the pH pressure and sacrificed themselves to protect the innermost cells. They lost their function but stabilise their microenvironment by correcting the pH locally and sustainably.”

Next steps

Andreas Walther’s team is currently collaborating with another team from Mainz to determine whether their prototissues could be used in cancer therapies, by providing lasting support for the immune system.