01 December 2021

Cyborg people

How is bioprosthesis changing

Fedor Senatov, Post-science

According to the Ministry of Labor, there are about 12 million people with confirmed disabilities in Russia, of which about 200 thousand people need prosthetics. Today's technologies allow not only to solve this problem cosmetically, but also to create functional prostheses with which a full life is possible. Special attention should be paid to bioprosthetics, which aims to create prostheses that are perfectly compatible with the patient from materials that fully reproduce the properties of various tissues of the human body — from bones to skin. Together with the candidate of Physical and Mathematical Sciences Fedor Senatov, we understand what is possible today, how bioprosthetics will change in the coming years and when it will be possible to print any new organ on a 3D printer.

Bionics, bioinspiring and biomimetics: educational program

Bionics is an engineering field of science that is responsible for using the properties and functions of wildlife in human technologies. For example, to create a vehicle, you can study the flight of a bird or the movement of a shark in the water, understand how this animal moves, and transfer the obtained parameters to man-made structures.

Bioinspiring is a more general term meaning the use of biological systems in solving engineering and technical problems. For example, the hexagonal shape of a honeycomb can be repeated in architecture. However, it does not necessarily have to be something functional: natural forms find their application in art.

Finally, biomimetics means repeating the structural features of natural materials and tissues to preserve all their properties. This is important when it comes to creating an ideal prosthesis: you first need to examine the tissue that will be prostheticized, and then repeat this set of parameters on a synthetic material. Then the prosthesis will be able to replace the missing fragment as efficiently as possible.

Peek at nature: what you need for a perfect prosthesis

 There are three groups of properties in nature that need to be repeated in order to reproduce the original object: anisotropy, hierarchy, dynamism. 

Anisotropy concerns the physical properties of an object, which change depending on the direction. For example, in human bone there are trabeculae — pores elongated in one direction. They determine the properties of the bone, and because of them it is easier to break it in one direction than in the other. If you look at a human bone lengthwise and across, it is an object with different properties.

The hierarchy can be explained by the example of a tree leaf: as a rule, it has a central vein, from which branches of small veins diverge in different directions. A similar hierarchy of structure also manifests itself in our circulatory system.

The third group of properties is dynamism, which describes the ability of natural objects to adapt to the environment. Leaves change color depending on the season, muscles increase in size, bones become brittle. This also includes regeneration, for example, the fusion of the skin on a cut finger. 

To create an ideal prosthesis, it is necessary to repeat all three groups of properties. So far, scientists are only trying to understand how this or that object works, and simply reproduce these parameters.

What elements of the human body can scientists repeat now

The best situation today is with hard tissues: bone implants can already be printed — both small fragments and up to 15 cm in size. The larger the implant, the higher the probability that traditional bioinert materials will be used for its production: titanium alloys, inert polymers like polyesterephyrketone. And if it is necessary to replace a small fragment, for example, in maxillofacial surgery, it will be made of bioresorbable materials that will gradually decompose in the human body and be replaced by their own bone.

At the same time, there are difficulties, because titanium implants have a large modulus of elasticity when compared with human bone. Therefore, the load, if it is the loaded part of the skeleton, is distributed unevenly and accumulates in the implant area. And then the bone surrounding it remains with a lower load, adaptability is activated — the body adapts to the changed loads. This leads to the fact that the bone on the border with titanium is embrittled and can break. Therefore, it is important not just to make a titanium implant, but also to repeat the microstructure and mechanical properties of the bone, the chemistry of the surface and material, to attract other cells there that will develop this part of the body.

I like to say that cages are like cats. The kitty can be put in a regular box, and she will like it there. The cells that come from our body to integrate with the implant should want to integrate it. They can feel good in a fairly cheap material if they are comfortable there in geometry and size. In addition, the cells cling better to the rough surfaces of the implants, they like them more. So is a cat that will climb into exactly the box that is comfortable for her in size, and not into the one that is more expensive or more elegant.

The situation with cartilage and joints is slightly worse in bioprosthetics. Now they are often simply changed entirely — this is the so-called total endoprosthetics. Hip, knee, shoulder joints can be replaced, but it is much more difficult to grow an artificial joint and help regenerating cartilage recover. Cartilage regenerates significantly worse than bone. 

Also, soft tissue prosthetics is just beginning to develop. Scientists have learned how to create muscles for implantation, even very small areas. The corneas of the eyes and elements of the circulatory system are printed on 3D printers, but this is only the very beginning of the path. Now it is still impossible to print the liver — you can only provide a general view of the organ, but not fully recreate its filtration functions. The printed pancreas must produce insulin, and this is much more difficult than simply repeating the structure of the bone. So in the field of soft tissue prosthetics, science still has a lot of work ahead.

How long does it take to create an implant

It depends on a large number of parameters, so the spread can be very large. For example, the Scientific and Educational Center of Biomedical Engineering of the National Research Technological University "MISIS" has been working on improving one implant for 12 years. If scientists want to develop an implant from scratch and bring it to market, then in ideal conditions it will take 6-7 years. 

There are several difficulties that increase this period. For example, if a product of local consumption is being created, in this case the state will not speed up registration procedures, and clinical trials may be delayed. If cellular materials are used in the implant, then Federal Law No. 180 "On Biomedical cell Products" is connected. 

On the other hand, if there are already materials that have been used many times in tests on laboratory animals, and it is necessary to choose the conditions for creating a specific implant, then it is possible to significantly reduce the time for creating an implant. So, scientists of the small innovative enterprise (MIP) "Biomimetics" together with the N.N. Blokhin National Research Center of Oncology prepared an implant for a cat with a tumor in the paw bone in just three weeks. During this time, an X-ray was digitized, a 3D model was made, a computer simulation was performed and a database of mechanical characteristics was uploaded to the computer. Then the weak points were corrected, the implant was printed, the surface was treated to make it optimal for the cells, and within 10 days the implant was populated with cells of a four-legged patient. The resulting prosthesis allowed the animal to live fully and actively for another year.

What materials are used in bioprosthetics

Four types of materials are used to create implants: synthetic, natural, cellular engineering and tissue engineering. Synthetic ones have already been mentioned — these are titanium, polylactide and many other materials. Natural polymers are, for example, collagen, which is widely used in plastic surgery. Cellular engineering structures are a more complex option, when scientists make a frame from a certain material (it can be either synthetic or natural), and then colonize it with the patient's stem cells. 

In the tissue engineering design, not cells are used, but the patient's tissues at once. For example, they print the skeleton of an organ, implant it under the skin and allow it to sprout with all the necessary tissues: blood vessels, connective tissue. For example, scientists at Sechenov University suggest using them to grow cells and tissues for the eardrum. To do this, they plan to use three components: stem cells that can divide and create specialized tissues, a polymer framework for tissue (it is called scaffold) and hormones that stimulate cell growth and development. 

Problems and trends of bioprosthetics

The peculiarity of prosthetics is that it is an interdisciplinary field, therefore the problems relate to different fields: materials science, biology, medicine, engineering science. Even IT can be included here, since big data plays an increasingly important role in prosthetics — arrays of information collected from scientific articles and clinical practices.

A modern implant is always individualized, the final version of the same bone will be different, depending on the age and gender of the person. But individualization in materials science and biology is understood differently. In materials science, this means the selection of the necessary mechanical characteristics, elasticity, correct microstructure and chemical elements. In biology, the interaction of implants with specific cells, tissues and organs is taken into account.

From the point of view of medicine, the problem is the integration of the implant, which was invented by scientists. And from the point of view of engineering science, it is important to solve the following tasks: how to assemble the bioprinter design correctly so that it does not spoil the cells during printing; how to maintain the right environment and sterility. 

The very method of bioprinting — an engineering approach that uses the achievements of biology, materials science and medicine — is one of the key trends in the creation of implants. In the future, they plan to use genetic engineering solutions more and more — for example, to create growth factors with the help of Escherichia coli (E. coli) bacteria. For example, NICEM Gamalei, the creators of the Sputnik V vaccine (or Gam-COVID-Vac), synthesized recombinant morphogenetic human bone protein artificially, using genetic engineering methods. That is, they received growth factors not from the human body, but created them artificially.

Cellular technologies, such as the use of stem cells, are another important trend in bioprosthetics. In recent years, there has been a lot of talk about induced pluripotent cells, in 2012, Briton John Gurdon and Japanese Shinya Yamanaka even received the Nobel Prize in Physiology or Medicine for their research. These are cells that can be taken from adipose tissue and returned to their original state. Then the cells become pluripotent, they have many development options, which means that they can potentially grow the right tissue.

Bioprosthetics and cyber prosthetics

Today, cyber prostheses are becoming increasingly common — one of the types of cybernetic manipulators, devices with which humanity has been familiar for several decades. These manipulators collect watches and equipment, sew clothes, and in recent years the principles of their construction have been used to create human prostheses. These can be cyber prostheses of individual limbs or whole exoskeletal structures. In October 2019, the media reported that with the help of an exoskeleton, a completely paralyzed person was able to walk more than 100 meters.

However, if it is necessary to do something that was not included in the program of the cyber prosthesis, its carrier is guaranteed to have problems. For example, if you need to walk up the steps or wave your hand counterclockwise, but there are no settings for these modes of movement, then nothing will happen. This intention is formed in the head of a person, the cyber prosthesis does not know about it. And this is one of the key problems of such solutions.

To solve it and allow the device to more accurately fulfill the will of the owner, scientists are working on the technology of brain—computer interfaces. With its help, prostheses and exoskeletons should understand brain signals and receive information directly, rather than referring to commands laid down in advance. Biomedical engineering comes to the rescue here: scientists propose to create very small conductive structures using biocompatible materials in order to use them to connect a nerve and a certain device, for example, the same cyber prosthesis.

About the author: Fedor Senatov – Candidate of Physical and Mathematical Sciences, Director of the Scientific and Educational Center for Biomedical Engineering of the National Research Technological University "MISIS".

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