Being a man who comes from tomorrow has advantages: if we want to explain in this way the more than 1400 patents registered by Robert Langer. But coming from the future can also cause problems of misunderstanding among contemporaries: “In the beginning they took me for crazy. Engineers like me were not highly regarded or valued in medical research,” recalls Langer, who is now a full-fledged pioneer. . And for his research on biomaterials, for having developed nanomedicine, with his innovations on the controlled release of healing molecules, he was awarded the 2022 Balzan Prize, which he will receive on November 25 in Rome from the hands of Sergio Mattarella.
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On several occasions you have proven yourself ahead of your time. What do you see today?
“Among the things that fascinate me most is regenerative medicine and in particular tissue engineering. That is to use stem cells to build new tissues and organs from scratch. With this approach we can build, for example, new skin for burns or new blood vessels for heart attacks.
And we may someday even have organs and tissues on a chip. This is an area that is still a little ahead of our time, but many teams are at work, including that of MIT. Another area where we will see great developments in the coming years is that of genetic therapies, which for me mean both gene editing with Crispr / Cas9 technology and medicine with messenger RNA that we used for Covid vaccines and with which Moderna is developing vaccine therapies against solid tumors “.
What was your contribution to tissue engineering, and what applications are drawn from your idea today?
“In the early 1980s the surgeon Joseph Vacanti and I proposed the idea of creating three-dimensional” scaffolding “that imitated the supporting structure of an organ or tissue and that allowed cells, if surrounded by the right means and the right stimuli, This is because if you simply insert stem cells into one place on the body, but don’t give them a supporting structure, the cells won’t be able to build a tissue or a piece of organ.
What we formulated was a fundamental principle, which was then followed and put into practice by many. And it has led to artificial skin and many other applications that are now in clinical trials, such as building new blood vessels, a new pancreas, and ways to regain hearing.
To facilitate the work, you can take a tissue (even from a donor) and remove the cells, leaving only the extracellular matrix, and then use this as a scaffold so that the patient’s stem cells can organize themselves into the necessary tissue. In other cases it may be that some substances produced by the cells may be useful as growth factors for stem cells. And the basic idea today also serves to make the so-called “tissues and organs on a chip”.
Researchers have already developed a gastrointestinal tract on a chip and a liver on a chip. And at MIT some of my students have created a “heart on chip”, while I, together with the neuroscientist Li-Huei Tsai, are developing a “brain on chip” “.
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What is the advantage of having organs (or parts of organs) and tissues on chips?
“It will speed up drug testing, avoiding the use of animals and shortening human clinical trials. With organs and tissues on a chip, thousands and thousands of experiments can be conducted in a very short time. And even more things can be learned about the biology of basis, because we will be able to study the response of our organs and tissues in conditions other than natural ones “.
1,400 patents licensed to over 400 pharmaceutical companies: how do you find inspiration?
“Often the ideas come to me looking at things in fields completely unrelated to medicine. One day, I was reading an article in Life, entitled” The cars of the future “: he explained that in case of dents on the hood due to an accident, one day, thanks to special materials, you can simply heat the dent and the metal will regain its original shape, making the defect vanish.
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It may sound like science fiction, but I knew it was a known phenomenon: the memory of form. So I thought: we could use the same principle to produce “smart” polymers to be inserted into the body. I discussed this idea with one of my PhD students, Andreas Lendleinand we started a project to create biodegradable materials with shape memory and activated both through a change in temperature and the effect of light, publishing several studies on Science e Nature“.
Can you give us some examples?
“If you have a wound to an internal organ and need a suture, today you need a surgical operation to open the space needed to stitch. We have designed a biodegradable thread that can be inserted into the body in a minimally invasive way and then activated. suitably, it can self-tie.
Another application is the removal of thrombus: just insert a needle into the blood vessel that penetrates the thrombus, and then let the polymer thread with shape memory come out from the opposite side. At that point you can activate it via laser and make it take on a spiral shape that allows, by withdrawing the needle from the vein, to drag the clot behind it, removing it “.
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Another application of his idea of ”shape memory” concerns the administration of drugs …
“The main problem with pills is that they cannot release healing molecules for more than a day, because stomach contents are evacuated daily. So those on a cure have to take pills every day, but many forget to do so. It would take a pill that succeeds. to remain in the stomach for several days.
And at MIT, together with Giovanni Traverso, we found a system to obtain this result: a capsule which, once in the stomach, thanks to the memory of the shape, takes on a star shape that has a larger diameter than the pylorus, i.e. the exit of the stomach. This way the pill gets stuck in the stomach and continues to release the drug. Having a star shape, it does not – of course – prevent normal stomach contents from passing through the pylorus. After the set 2-3 weeks, the capsule biodegrades “.
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Is there any more frontier solution on the horizon?
“The RoboCap: a robotic capsule. Physical conditions in the gastrointestinal tract can severely limit the effectiveness of oral medications. It is for this reason that diabetics cannot take insulin in pill form – orally, insulin has a lower bioavailability than” 1% – but they have to inject it.
Our robotic capsule, once ingested and arrived in the intestine, is activated and thanks to a helical structure it begins to rotate, cleaning the place where it is from the mucus. At that point he can release the drug, which is thus absorbed in the ideal quantity. Animal experiments show that with RoboCap we significantly raise the concentration of insulin in the blood. “
Born in Albany in 1948, Robert Samuel Langer Jr., chemical engineer, is a giant of biotechnology and more: he is the most cited engineer in history and is the third most cited scientist ever. He has registered over 1,400 patents and is co-founder of over 40 biotech companies: the most famous is Moderna. The Langer Lab at MIT in Boston is the largest biomedical engineering laboratory in the world.