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New approaches to safe implantation

September 25, 2020

Мedicine has proposed many solutions, including implants, transplants, and various implantable biomedical devices for the treatment of a wide range of human pathologies.

The main task of scientists is to minimize complications caused by implanted objects in the human body. Negative consequences can also be expressed in poor acceptance and in the progress of chronic inflammation.

We are going to tell now what scientists of the Project 5-100 universities offer in order to help patients avoid postoperative complications.

Scientists of Tomsk State University explore the surface properties of implants and research new materials and technologies for sustainable immune tolerance.

The scientists conduct research on reducing implant rejection in the laboratory of translational-cellular, molecular, and biomedicine at TSU in two areas: first, they conduct experiments on modifying natural polymers for better integration with patient tissues, and second, and they select methods of immunomodulation to control the body's reaction to the introduction of the implant.

In the first area, for example, natural polymers (collagen, hyaluron, alginate, chitosan, etc.), which have a composition similar to the tissues of the human body, are applied to the implant. Scientists have found that this similarity accelerates the recovery process.

The second approach is aimed at making macrophages more slowly recognize the implanted object as foreign. Scientists are trying to create a coating on the implant that minimizes protein adsorption that is protein immune cells will not be able to stay on it and instantly react negatively.

In addition to the above-described physical approaches to impact on the surface of the implant, there is also a chemical one using hydrogels. The hydrogels are polymer scaffolds capable of retaining large amounts of fluid, as well as transporting nutrients and biologically active molecules. They allow you to interact more gently with the living tissues. The advantage of hydrogels is that they can be loaded with cytokines (proteins of activated cells of the immune system), which can regulate the release of immunomodulators around the implant. Scientists can also change the chemistry of the hydrogel, change the cell size in the gel, the degree of crosslinking, and the rate at which nutrients are released.

The main goal of the laboratory is to find the most effective and safe way of physical or chemical action on the surface of the implant for favorable engraftment.

The Research Educational Center “Additive Technologies” of TSU have been developing a technology for a full cycle of production of dental pins (implants) from a reliable hypoallergenic material - nanostructured ceramics based on zirconium dioxide for 5 years.

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Credits: TSU Press-office (Vladimir Promakhov)

“We worked on this project in an evolutionary way: first we learned to work with high-quality Japanese materials: we studied the sintering kinetics, the structural-phase states of these materials, and understood what kind of materials they were. Then we worked out the processes in the production of parts at the request of enterprises - all these are products of complex shape. After analyzing the market, we realized that the demand for dental implants was very large, and our experience allows us to produce them”, - said Vladimir Promakhov, PhD, Deputy Director of the REC "Additive Technologies" of TSU.

Small-scale production is already launched at the educational center. Negotiations are underway with dental clinics specializing in prosthetics.

MISIS develops an integrated approach to ensure the existence and functioning of the implant in the body without negative consequences and at the same time with the ability to induce specific cellular reactions.

“There are many factors that affect how successfully and quickly an implant will take root in the human body. Depending on the type of implant, on what tissue/organ it replaces, different requirements are imposed on it in terms of mechanical strength, elasticity, microstructure, the presence of bioactive components, etc. Biocompatibility is a general requirement. The implant may not lead to the development of a rejection reaction, doesn't release toxic substances and exist for a long time in the body without significant changes, but at the same time not integrate with the surrounding tissues. We need to talk not about 100% safety, but minimizing the negative outcome”, - comments Fedor Senatov, Ph.D., Head of the iPhD Biomaterial Science Program, NUST MISIS.

Using a bone implant, as an example, MISIS proposes the following methods:

1) To select some materials with biological activity, contributing to the accelerated process of integration thereof in bone tissue. For example, use bioceramics based on calcium, phosphates, silicon. Thus, the Center for Composite Materials of NUST MISIS proposed a method for the synthesis of bioactive ceramics — diopside — from eggshells, followed by an introduction into a medical polymer.

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Credits: NUST MISIS Press-office

2) To reproduce the architecture of natural bone. Bone has a complex porous structure. If you accurately simulate the size and geometry of the pores and ensure the desired wettability, then you can create conditions for the attachment of cells from the body and therefore improve the survival rate. Biomimetic approaches have been successfully applied in the development of a porous implant based on ultra-high molecular weight polyethylene.

3) To reproduce the mechanical properties of bone tissue. If the modulus of elasticity of the implant is greater than the modulus of elasticity of the bone, the effect of stress shielding will occur, leading to remodeling and embrittlement of the surrounding bone, which can lead to its secondary damage. The NUST MISIS Center for Composite Materials proposed a polymer implant with mechanical properties similar to natural bone.

4) To implant protein growth factors. A group of researchers from NUST MISIS and National Medical Research Center for Electrochemistry named after N.F. Gamaleya developed an implant with the injected BMP-2 bone protein, which significantly accelerates the integration thereof in bone tissue.

5) To create cellular or tissue-engineered structures that will immediately contain the cells/tissues of the patient himself, which will improve the survival rate. A group of researchers from NUST MISIS and National Medical Research Center of Oncology named after N. N. Blokhin has developed a cell-engineered structure used in clinical cases in veterinary medicine.

“An important approach to the creation of the implant with given properties, of geometry, load, sex, age, concomitant diseases, etc. After all, there may be a case when a person has an individual reaction to any component of the material”, - notes Fedor Senatov.

Far Eastern Federal University also supports an individual approach to treatment, because the complications that depend on the implant itself, in general, have already been minimized in world practice. Valery Tolmachev, MD, Ph.D., Maxillofacial Surgeon of the Medical Center of Far Eastern Federal University notes: “Complications occur when using any implants, as for dental implants, the proportion of complications, as a rule, does not exceed 2%. Another thing is that the quality of such complications has changed for the better; specialists with a timely treatment of patients can deal with most of them. In order to reduce the number of complications of implantation, it is necessary to plan and predict the outcome of the intervention using such modern examination methods as multispiral and cone-beam computed tomography; magnetic resonance imaging, and other methods of medical imaging; study of the patient's immune status, including using immunohistochemical methods and a number of other innovative diagnostic techniques, according to indications for their use.

There are often alternative treatments without the use of implants exist. If the patient is not sure that he will be able to follow all the recommendations related to the rules of the implant functioning, then it is better not to resort to this method.”

These alternative methods include the seemingly fantastic but already quite real experiments of scientists on growing teeth from stem cells! A year ago, in the Department of Fundamental Medicine of the School of Biomedicine of FEFU, while studying the early stage of the development of the oral cavity of the embryo during the period of tooth formation, researchers were able to identify several types of cells involved in the formation of the enamel organ, which, in fact, is the tooth rudiment. They also found out that the crown of the tooth, and its root was formed in different ways. This discovery contributed to further research at FEFU, which is now focused on the development of bioengineering techniques in dentistry, or rather, on the growth of new dental tissue.

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Credits: Primary tooth under microscope (stomatologclub.ru)

However, as the results of recent experiments demonstrate to us that it is still too early for us to say that it is possible to grow a tooth only from stem cells. The dentin-coated specimens still lack full-fledged enamel. For a successful result, scientists need a more fundamental knowledge of intercellular interactions during tooth formation.

The universities of Project 5-100 will further develop new bioengineering approaches in regenerative medicine, as well as look for ways to minimize possible complications from implantation, but due to the complexity of the task, this direction may take years. Therefore, we remind you that the best treatment is prevention!