02 October 2015

New materials and fabric engineering

MIT Professor Robert Langer on the ways of forming new tissues, polymer frameworks and the use of computer technology in biology.

Tissue engineering largely began with research conducted many years ago by me and Javier Conte, who now heads the Department of Pediatric Surgery at the Massachusetts General Hospital. Besides us, many other people participated in it. The basic idea of tissue engineering is to combine materials and mammalian cells, including stem cells, to form a new tissue or organ. There are several strategies that we are working on together with other scientists.

One strategy that may be able to help in the fight against diabetes is the following: you take, say, islet cells and put them in a capsule made of a special material, thereby preventing immune rejection. So, for this method you will need a special material, such as alginate, or something else. You take the cells of this material, put them in water and then use a syringe to inject them into a calcium bath, that is, a bath with ions of a certain type. This leads to helification. This way you get something like beads, each the size of a pore. The cells are inside these beads, and the following happens (I'll show it with the example of diabetes): insulin passes through some pores, and glucose passes through others, while antibodies and immune cells cannot penetrate the capsule due to their large size, so the inside of the bead is protected from them. So you can put a small artificial pancreas in a microcapsule, and that's great, isn't it?

However, difficulties may arise with this method: in some cases, a fibrous membrane forms around the microcapsules, preventing the passage of insulin and glucose. Therefore, Dan Anderson and I have made one of the main directions of our laboratory's work the creation of superbiocompatible materials, as I call them, that will not be enclosed in a capsule. Now, together with the Foundation for Research in the Field of Diabetes Mellitus in Adolescents, we are conducting experiments on primates to test the results. It was an example of already existing and applied material.

The next direction in tissue engineering is polymer frames, which can be given any shape. Cells can be placed on them, and as soon as they are there, they self-organize, forming a new tissue or organ. It can be cartilage, bone, new skin for burn victims or patients with diabetic ulcers. To do this, you need to do the following things: the first is to create materials to which cells can be attached, and the second is to create a structure of a suitable shape and structure. For example, when creating cartilage, you can shape it into a nose or ear, depending on your goals. Or you can also give the polymer certain properties, such as elasticity. And then the cells are placed on polymer scaffolds, grown and turned into tissue. Already, this technology is being used to create skin instead of burnt, to create objects of various clinical trials, including cartilage, cornea, and even, possibly, to restore the spinal cord. However, this area has a very wide application.

The issue of materials is acute in many of these areas, both from the point of view of chemistry and from the point of view of production. Speaking of chemistry, I'll just list a number of potentially useful materials that we – and a number of other scientists – are trying to create. The first: a biocompatible material capable of joining with the help of ionic bonds – to solve the problem of diabetes. Second: materials with certain amino acids facing outward. They are useful for attaching certain types of cells, such as neurons. Third: materials with the required elasticity, necessary for some parts of our body, such as blood vessels, which are very elastic. Fourth: materials that allow cells, including stem cells, to differentiate, that is, to turn into any desired type of cells. There are a number of other chemical problems related to materials.

There are also production problems: how to give the right shape, the right structure. A number of techniques are used to solve some of them.

For example, 3D printing has received a lot of attention recently, because it allows you to create very complex designs, but it is not limited to it.

There are many other ways to create structures, fibers, and nanostructured systems. So there are still many unsolved problems and problems in terms of materials – both chemical and industrial.

One of the most important such problems is the issue of material safety, but when working with innovative chemical solutions, it can only be confirmed by testing. Secondly, materials should interact well with cells and do it the way you want. Thirdly, in many cases, materials must decompose naturally, because we do not need eternal materials - we want them to do their job and then disappear. And, of course, when you combine materials with cells, their interaction can also lead to all sorts of consequences – for example, tissue reactions or other undesirable things. I would say that tissue engineering in this regard is more experimental than theoretical science. That is, of course, there are theoretical works, but there is still no complete understanding of how to grow a tissue or organ, so many experiments are being conducted with various materials, cell types, methods of growing them, experiments on animals, sometimes on humans. It seems to me that we cannot do with the already existing volume of theoretical knowledge in this area, so we have to experiment so much. Take immune rejection or why a fibrous membrane is formed. We simply don't know much, or we don't know enough about the causes and mechanisms of such phenomena. Yes, I would say, unfortunately, our knowledge is scarce. And if so, then we have to rely on empirical knowledge.

In my opinion, in order to use computer technology productively in biology, we need a theoretical basis. For example, they helped in decoding the human genome, because they managed to construct DNA sequencers and develop a sufficient understanding of what to do. And when it comes to a biological process that is not fully understood, it is very difficult to use computers, because you simply cannot program it. So I would say that a number of scientists – including us – are currently working on creating new tissues, we can already create skin (although we could work more efficiently if we understood the necessary things better) for transplantation to patients with diabetic ulcers and burn victims. We are also testing the possibility of creating cartilage, intestines, vocal cords, spinal cord. I think there are still many serious tasks to be solved. We – and a number of other scientists – are working on them.

Let's look at the encapsulation of pancreatic cells. The main problem with them is that if you enclose cells in a polymer shell, then a tissue reaction will occur, and this is a serious problem, since it prevents the passage of molecules into and out of the capsule. So even if insulin is produced, it will remain in the capsule. So we need a material that has high biological compatibility (and does not cause tissue reactions), or somehow prevent the formation of a fibrous membrane. Specialists working on the problems of tissue engineering come from different fields: these are chemical engineers, biologists, materials scientists, surgeons, and cytologists. The field is very interdisciplinary. And I think it's great, because they learn from each other: a chemist-engineer learns something from a biologist, and vice versa, a biologist learns from a chemist.

Tissue engineering is a promising field of research, there are a huge number of diseases that cannot be treated with medication, and if it turns out to help people with liver diseases or diabetes, or restore their spinal cord, it will be a real breakthrough. In my opinion, what is happening in science now is truly innovative and exciting, for example, excellent biological research, stem cell research, excellent materials research. In general, tissue engineering is a very promising field for both science and medicine.

About the author: Robert Langer Professor of Chemical and Biomedical Engineering, Massachusetts Institute of Technology.Portal "Eternal youth" http://vechnayamolodost.ru

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