What will be the implant of the future?
Bone implants
Fedor Senatov, Post-science
Every year, hundreds of bone implant surgeries are performed in the world, the need for which appears due to injuries sustained as a result of an accident, other accidents or illness - for example, due to the development of osteosarcoma, when the surgeon removes part of the bone tissue and puts a bone implant in its place.
Each of us has seen the complex structure of the bone: inside it is porous, and the outer layer is solid. The bone consists of different layers, each of which carries its own functional load. If the inner layer is spongy, then it is the trabecular bone through which nutrients pass, blood vessels germinate. The cortical bone has high strength and other properties, it carries a heavy load, so our skeleton carries us, supporting internal organs. The cortical bone has a small pore size. If we want to replace a real bone, we need to reproduce these structures in order to completely replace the lost part of the bone, which is why interest in the subject of bone implants is so high.
The area of bone implants is complex and complex. First of all, it is necessary to select a material that is chemically close to bone tissue or contains the necessary bioactive components, because our bone is involved in the vital activity of the body. The bone consists of collagen fibers, which give elasticity, and mineral hydroxyapatite – a chemical compound of calcium, phosphorus, oxygen. If we create an implant from such chemical elements as calcium, phosphorus, then we will be able to achieve chemical similarity with bone tissue and provide functional characteristics. Now hydroxyapatite is obtained from crushed bones or chemically synthesized and injected into the structure of implants. If an implant with such components is introduced into the body, it will immediately see the necessary chemical elements in front of it for the fastest possible fusion.
The problem with modern implants is that they do not fuse well or the body has undesirable reactions to foreign objects, so the requirements for bone implants are severe. First of all, the biocompatibility and bioactivity of the material. At the same time, it must be bioresistant, not deteriorate when implanted into the human or animal body. The implant must have mechanical properties. This is a big problem for modern implants. Titanium alloy-based implants are now common. From the point of view of strength and biocompatibility, these are good implants, but they have a noticeable drawback – high rigidity. If the difference between the modulus of elasticity of the bone and the modulus of elasticity of the implant is high, then bone remodeling occurs – a phenomenon when the bone remains unloaded and the rigid part of the implant takes over the load, so the bone weakens, the risk of secondary fracture increases. Therefore, the efforts of materials scientists are aimed at selecting the necessary properties of implants that are as close as possible to real bone tissue.
In modern medicine, titanium-based, magnesium-based implants, polymer implants based on inert materials are used: polyesterephyrketone, ultrahigh molecular weight polyethylene. Other implants are created on the basis of bioresorbable materials: polylactide, polyhydroxybutyrate, polyglycolides. There are many options. Bioresorbable materials are a separate interesting topic, because there are situations when it is necessary to replace a piece of bone tissue for a short period of time, and after that the body itself will be able to grow a new bone. For such purposes, implants are created that dissolve in the human body, decomposing into water and carbon dioxide, and their own bone grows in their place. The most advantageous structures of the bioresorbable material are structures including calcium, phosphorus, hydroxyapatite or calcium phosphate, octacalcium phosphate. Now bioresorbable materials are created on the basis of metals. For example, magnesium is able to oxidize under the influence of biological fluids and gradually dissolve, despite the fact that it is an important element that the body needs. The main problem for magnesium is the rate of resorption (resorption), because during it hydrogen bubbles are released, which have a negative effect on the body and on the process of fusion of the implant with bone tissue.
Choosing the right material and chemical composition is only the first part of the job. Another important factor is to simulate the structure. The structure of bone tissue is diverse. If we want to reproduce a porous or spongy bone, it is necessary to create pores of a certain size and shape in the material, because bone cells have dimensions of several tens of micrometers. Blood vessels have different sizes, so porosity should ensure the germination of the right types of tissue for maximum integration of the implant with the body.
An example of an implant is a hybrid – the combination of dissimilar materials, such as polymer and metal, in one implant. The hybrid implant of the tubular bone will be porous inside, then there is a layer of metal that takes on the load, and then a polymer layer with the desired bioactivity. Biomimetics is engaged in such imitation of real bone tissue (from the words βίος and μίμησις – reproduction of natural structures). Modern technologies, including 3D printing, have made it possible to reproduce not only the microstructure, but also the external geometry, which is very important when installing implants. When an implant is installed, it is important that its boundaries coincide with the bone tissue, the congruence of the border is observed. With the help of computed tomography, they learned to scan the place for the future implant, then they print it using a computed tomogram. For example, an implant that is installed to a cat with osteosarcoma consists of a titanium alloy printed on a 3D printer. A highly porous material imitating a spongy fabric was placed inside the base, and an insulating layer of polymer was placed on top. Such a hybrid allows not only to imitate the internal structure, but also gives an external resemblance to bone tissue.
When creating a hybrid, implants are obtained that make up for large structural defects. For example, using a combination of a metal mesh and a porous implant. A patch made of such materials can carry a load, but also quickly coalesce due to the porous part. To accelerate the implant's engraftment, growth factors are introduced into it – protein molecules that allow activating the growth of bone tissue. Proteins BMP-2, TGF-beta, growth factors that stimulate the formation of blood vessels are used. Such signaling molecules shout to the bone tissue cells that they need to get closer and start building new bone tissue.
Signaling molecules are not the only way to speed up the implant healing process. Currently, cellular engineering and tissue engineering implants are used in science. To create the first, the patient's cells are used, for example, from the bone marrow. These are mesenchymal multipotent stromal cells that have not been fully determined, so bone tissue, cartilage, and adipose tissue are obtained from them. If you put these cells inside the implant on the right surface, they will begin to differentiate in the right direction. This differentiation is stimulated by the introduction of growth factors or the creation of the right environment. Working with such implants is the cutting edge of biomaterial science. The efforts of biologists, materials scientists, and physicians are aimed precisely at creating optimal cellular engineering structures that will allow us to create bone tissue cells inside the implant. The next step is the creation of fabric–engineered structures. The skeleton of the future bone tissue is taken, made of synthetic materials that have the desired pore anisotropy – pores in the form of elongated trabeculae. If you reproduce this structure – scaffold, frame – such a frame can be combined with fabrics. With the help of 3D bioprinting, the skeleton can be combined with cellular spheroids, which will integrate with each other and create future bone tissue on the surface of the skeleton.
Another problem associated with implantology is the attachment of infections. Now 15-20% of operations end with the addition of infections. This is combated by applying antibiotics or other antibacterial substances to the surface of the bone implant, but they reduce the rate of osseointegration and can negatively affect the cells of the body. The technology of supercritical fluids is associated with the introduction of the necessary antibacterial substances into the implant. This is a state of matter that allows good penetration into solid and non-porous materials. With the help of supercritical carbon dioxide, the antibiotic molecules are forced to penetrate the non-porous implant. These molecules gradually come to the surface of the implant and slowly kill the necessary microorganisms, rather than acting with the whole dose at once. With the help of this technology, not only antibacterial substances can be injected into implants, but also antitumor drugs.
Now 4D printing is becoming another important area in which people work with bone implants. 4D printing is 3D printing, where materials with shape memory are used. From such materials, a bone implant can be printed in the form of a compressed form, placed in a bone defect, and under the influence of the temperature of the human body, this implant will straighten out, tightly fitting into the bone defect. The implants will become self-installing, and minimally invasive operations will be performed to install them. Now this technology is at the stage of laboratory research, it provides potential opportunities for the use of new materials in implantology.
About the author:
Fedor Senatov is a candidate of Physical and Mathematical Sciences, an employee of the Research Laboratory of Hybrid Nanostructured Materials, the Research Center for Composite Materials of NUST MISIS.
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