WO2018038624A1

WO2018038624A1 - Composite carbon nanomaterial for repairing bone defects, a method for producing same, and an implant made from composite carbon nanomaterial

Info

Publication number: WO2018038624A1
Application number: PCT/RU2016/000562
Authority: WO
Inventors: Олег Викторович БАРЗИНСКИЙ; Сергей Константинович Гордеев; Игорь Михайлович БЕЛОВ; Светлана Борисовна КОРЧАГИНА
Original assignee: Олег Викторович БАРЗИНСКИЙ; Сергей Константинович Гордеев
Priority date: 2016-08-22
Filing date: 2016-08-22
Publication date: 2018-03-01

Abstract

In the invention, a biocompatible porous composite material for repairing bone defects is proposed which has elastic characteristics that approximate the properties of bone. The material comprises a pyrocarbon matrix and a fibre shell that consists of carbon fibre rods oriented in 4 directions. The mean size of the graphite-like fragments in the structure of the material is less than 30 nm, the mass fraction of carbon fibres in the structure of the nanomaterial is 30-38%, the open porosity of the material is not less than 5 vol.%, and the elastic modulus of the nanomaterial does not exceed 15 GPa. A manufacturing method consists in treating a shell assembled from carbon fibre rods in a gaseous medium of a hydrocarbon and 2-45 vol.% of hydrogen at a temperature greater than the decomposition temperature of the hydrocarbon, wherein the process of forming the pyrocarbon matrix is carried out at a temperature gradient inside the shell of 10-100 C/mm. An implant for repairing bone defects is made from a composite carbon nanomaterial containing a pyrocarbon matrix and a multidirectional reinforcing shell made of rods formed from carbon fibres arranged along the axis of the rods, wherein the implant material has an elastic modulus of no more than 15 GPa, the mass fraction of carbon fibres in the structure of the nanomaterial is 30-38%, the open porosity of the material is no less than 5 vol.%, and the mean size of the graphite-like fragments in the structure of the material does not exceed 30 nm.

Description

COMPOSITE CARBON NANOMATERIAL FOR REPLACING BONE DEFECTS, METHOD FOR ITS PRODUCTION AND IMPLANT FROM

COMPOSITION CARBON NANOMATERIAL

The technical field The invention relates to medicine, namely to surgery, traumatology and orthopedics and can be used in the surgical treatment of inflammatory, degenerative-dystrophic, oncological bone diseases, as well as bone injuries.

BACKGROUND OF THE INVENTION At present, materials of various classes are used for the manufacture of implants: metals (titanium), ceramics (aluminum and zirconium oxides, bio-metals, hydroxyapatite) and some synthetic polymers (high molecular weight polyethylene, polymethyl methacrylate, etc.).

Metallic, polymeric and many other materials used as implants have a number of disadvantages. Numerous studies have shown that the use of metal implants - especially for inflammatory bone diseases - often leads to resorption of bone tissue, and metal ions, diffusing into surrounding tissues, cause their damage - metallosis. The disadvantages of metal implants include fatigue of metals and their susceptibility to corrosion.

Many polymeric materials do not have biological inertness and are subject to biological aging, during which these materials can release toxic and carcinogenic products. Most importantly, they cannot be used to replace a large group of bone defects, because their mechanical properties do not provide support for the operated area.

Ceramic materials, having many advantages, are too fragile and have a high modulus of elasticity compared to bone tissue, which does not allow smooth transfer of the load from the implant to the bone and, ultimately, leads to bone resorption.

Known carbon composite porous material for the replacement of bone defects (RF patent N ° 2181600), which is the closest analogue to the invention. The material consists entirely of carbon and is a durable, porous composite with biocompatibility. Known material contains in its structure a reinforcing base and matrix. The reinforcing base is made in the form of a frame containing vertically mounted rods and horizontal layers, each of which is formed by rods. The rods of each layer of the frame are oriented relative to the rods of the subsequent and previous layers at an angle of 60 °. The rods are molded from carbon fibers. The matrix of the material is made of pyrocarbon.

A method of manufacturing a known composite material consists in forming a reinforcing base and subsequent deposition of a pyrocarbon matrix. The reinforcing base is formed in the form of a frame assembled from rods molded from carbon fibers. The frame is first assembled in layers, orienting the rods parallel to each other in each layer and at an angle of 60 ° with respect to the rods of the previous and subsequent layers. After assembling the required number of layers, vertical rods are installed in the formed vertical channels. The pyrocarbon matrix is precipitated by treatment with gaseous hydrocarbons at a temperature exceeding the temperature of their thermal decomposition.

A disadvantage of the known composite material is its relatively high stiffness: the modulus of elasticity of the material - 30-0 Sha - significantly exceeds the modulus of elasticity of the bone tissue (12-15 Sha), which reduces the effectiveness of the use of implants made from it.

Disclosure of invention

The objective of the invention is the creation of a biocompatible porous composite material for the replacement of bone defects with elastic characteristics close to the properties of the bone, a method for producing such material and implant options for the replacement of bone defects.

The technical result is achieved in a combination of composite carbon nanomaterial, a method for its manufacture and an implant made of composite carbon nanomaterial as follows:

Composite carbon nanomaterial for bone defects replacement includes a pyrocarbon matrix and a fibrous reinforcing base made in in the form of a frame of rods containing carbon fibers oriented along the axis of the rods, and containing vertically mounted rods and horizontal layers, each of which is formed in parallel by oriented rods, and the rods of each layer are oriented relative to the rods of the previous and subsequent layer at an angle of 60 °. The average size of graphite-like fragments in the structure of the material is less than 30 nm, the mass fraction of carbon fibers in the structure of the nanomaterial is 30-38%, the open porosity of the material is at least 5% by volume, and the elastic modulus of the composite nanomaterial does not exceed 15 GPa.

The reinforcing structure formed in the material in the form of a framework of rods containing carbon fibers is connected by a pyrocarbon matrix into a single composite nanostructured material. This material contains many regularly located pores. The material possesses not only high mechanical properties - compressive strength of more than 30 MPa, which is a consequence of the structural features of the reinforcement and properties of the pyrocarbon matrix, but also biocompatibility and good workability, which is ensured by nanostructured carbon, which allows the use of material for the manufacture of bone implants. It is important that the carbon structure of the material, constructed from graphite-like nanofragments with a size of not more than 30 nm, provides the material with an elastic modulus of not more than 15 GPa, which maximally approximates the properties of implants to the properties of the replaced bone, and the open porosity existing in the material is not less than 5% vol. - ensures the fixation of implants made from it due to the ingrowth of the newly formed bone into the porous structure of the material and thus the formation of a bone-carbon block. In this case, the presence of an open one, i.e. communicating with the surface, porosity, which, as shown by experiments, is active for the formation of newly formed bones in the pore volume.

The macro- and nanostructure of the manufactured carbon composite nanomaterial is formed due to the technological features of its production, implemented in the proposed method for its manufacture. In this case, not only dimensional features of graphite-like nanofragments that determine the structure of the material and its elastic properties are achieved, but also such properties as open porosity, density, and mass fraction of carbon fibers in the material. When the modulus of elasticity of the carbon composite nanomaterial is more than 15 GPa, its elastic properties exceed the elastic properties of the bone, which reduces the effectiveness of the use of the material, or rather implants from it, when replacing bone defects, because high rigidity of the implant material does not allow smooth transfer of the load from the implant to the bone and vice versa, which ultimately leads to bone resorption.

With an average size of graphite-like fragments in a carbon nanomaterial of more than 30 nm, it is not possible to realize a material structure that provides an elastic modulus of less than 15 GPa.

With an open porosity of carbon nanomaterial less than 5% vol. the osteoconductive properties of the material are reduced - implants made of such material are worse fixed in the bone bed by the newly formed bone tissue.

The mass fraction of carbon fibers in the structure of the nanomaterial is 30-38%. This interval provides a combination of the elastic modulus and porosity of the material in the ranges indicated by us. In addition, the proposed interval of the mass fraction of carbon fibers is associated with technological features of obtaining the material, primarily with the preferred density of the assembly of the reinforcing carcass when implementing the method of manufacturing the material: with a low content of carbon fibers in the material structure, the reinforcing carcass is more porous and loose, which makes it difficult stages of obtaining composite nanomaterial, and the obtained material itself has low mechanical properties - ultimate compressive strength below 30 Pa, which is unacceptable when used for the manufacture of implants. The same can be said about higher than the indicated content of carbon fibers. In this case, a too dense carbon fiber framework is obtained, which complicates the implementation of the subsequent stages of obtaining nanomaterial. Preferably, the diameter of the rods containing carbon fibers is 0.7-2 mm. When using rods with a diameter of more than 2 mm, the reinforcing base has a loose large-pore structure, less preferred for making implants for replacing bones from such material. When the diameter of the rods is less than 0.7 mm, the laboriousness of manufacturing the reinforcing base increases significantly due to the fact that the number of rods needed to assemble the frame increases. Preferably, the composite material has a density of 1.2-1.8 g / cm ³ . The lower density of the material is due to its increased porosity and leads to a decrease in the strength of the composite material, which is unacceptable when used to replace bone defects. The porosity of materials with a density above 1.8 g / cm is too low to allow the growth of newly formed bone blocks into the material in the postoperative period of bone defect replacement.

A method of manufacturing a composite carbon nanomaterial for the replacement of bone defects involves forming a reinforcing base in the form of a frame by layering rods formed of carbon fibers oriented along the axis of the rod, arranging the rods in each layer parallel to each other and at an angle of 60 ° with respect to the rods of the next and previous layers, until the required number of layers is reached, with subsequent laying of additional rods in the formed vertical channels, and the subsequent formation of mat by precipitation of pyrocarbon from a gaseous medium containing at least one hydrocarbon at a temperature higher than its decomposition temperature, while the gaseous medium additionally contains hydrogen in an amount of 2-45% vol., and the process of forming a carbon matrix is carried out with a temperature gradient inside frame 10-100 ° C / mm.

When implementing the method of manufacturing the material, fibrous reinforcing elements are used to form the reinforcing carcass — carbon fiber rods oriented along the axis of the rods, which ensures the most complete realization of the elastic modulus of the carbon fiber without damaging its structure. To obtain the rods, in particular, pultrusion technology can be used, including: - impregnation of carbon fibers with a polymer binder to form a tow,

- pulling the tow through the die to obtain the desired cross-section of the rod,

- curing the binder.

The optimal conditions for the production of carbon fiber reinforcing elements are determined by varying the concentration of the polymer binder solution, the temperature of the curing ovens, the speed of the bundles through the spinneret block. From the rods molded from carbon fibers, a carcass on a mandrel is assembled layer by layer (Fig. 1). At the first stage of assembly, the guiding rods are installed vertically in the holes along the perimeter of the mandrel, then the horizontal layers are assembled, setting the rods in the layer parallel to each other and at an angle of 60 ° with respect to the rods of the previous and subsequent layers (Fig.2). After laying the horizontal layers to the desired height, additional rods are installed in the formed through vertical channels (Fig. 3).

To simplify the assembly of large-height frames, it is preferable to assemble the frame as follows. After the assembly of the carcass layers from the rods to a predetermined height in this way, as described above, vertical rods are installed that are longer than the height of the assembled layers. Then continue to assemble the layer of the frame from the rods according to the same technological scheme, placing them in this case between the vertical rods. This simplifies the assembly of the reinforcing frame of high height, because the installation of vertical rods in the frame is a certain difficulty due to the fact that it is necessary to ensure accurate positioning of all rods in all layers of the reinforcing base. Any failure leads to the inability to install a vertical rod due to the overlap of the vertical channel with rods lying in the layer.

After completion of assembly, the frame is removed from the mandrel and the pyrocarbon matrix is synthesized.

A frame of rods molded from carbon fibers is placed in a reaction chamber and a pyrocarbon matrix is formed in a medium containing gaseous hydrocarbon (s) and hydrogen. To ensure uniform filling of the reinforcing base with a nanostructure pyrocarbon matrix, the matrix formation process is implemented in a temperature gradient of 10-100 ° C / mm. The use of a temperature gradient in the synthesis of pyrocarbon inside a porous framework allows the synthesis of the matrix to be realized in a limited space of the framework — only where the temperature of the framework exceeds the decomposition temperature of the hydrocarbon used. For this, for example, a heater is installed along the axis of the assembled frame, for example, in the form of a tube of carbon-graphite material, through which an electric current is passed. By heating the heater and cooling the outer surface of the frame, a temperature gradient is established in it. Thus, a zone is created in the reinforcing cage elevated temperature, where the temperature exceeds the decomposition temperature of the hydrocarbon. This zone is located near the heater; therefore, the matrix formation process occurs only here. Raising the temperature of the heater in accordance with the optimal conditions for obtaining material, move the zone of the process of synthesis of the pyrocarbon matrix from the heater to the periphery of the processed frame, for example, at a speed of not more than 5 mm / hour.

Low molecular weight hydrocarbons (methane, ethane, propane, acetylene, benzene, etc.) and their mixtures, for example, natural gas, at an elevated temperature, usually in the range of 550-1200 ° C, can enter into a heterogeneous chemical decomposition reaction with the formation of carbon. The course of the decomposition reaction in the pores of the carbon fiber framework ensures the formation of a pyrocarbon matrix. To obtain a carbon composite material containing graphite-like fragments less than 30 nm in size, the synthesis of the pyrocarbon matrix in the present invention is carried out from a hydrocarbon-hydrogen mixture with a hydrogen content of 2-45% vol. The use of a gas mixture when producing a composite carbon nanomaterial with a hydrogen content of less than 2% does not ensure the formation of the required structure of the pyrocarbon matrix. With a hydrogen content of more than 45% vol. the matrix formation process is very slow due to a significant decrease in the concentration of hydrocarbons in the gas medium. The formation of a uniform structure of a pyrocarbon matrix with an average size of graphite fragments of less than 30 nm is provided during the process from a hydrogen-containing gas mixture with a temperature gradient within the framework of at least 10 ° C / mm. The implementation of the synthesis process with a temperature gradient of more than 100 ° C / mm is technically difficult due to the thermophysical problems of creating such a temperature gradient in a reinforcing base. The synthesis of the pyrocarbon matrix is carried out in a special chamber, which is equipped with means for supplying, regulating and measuring gas flow. The temperature regime, gas flow rate and the process time are chosen so that the resulting composite material preferably has a density of 1.2-1.8 g / cm, while the open porosity is at least 5% of the volume of the material, and the average size of graphite-like fragments in the structure of the material did not exceed 30 nm.

The presence of hydrogen in the gas mixture limits the course of the processes of homogeneous decomposition of hydrocarbons occurring with the formation of carbon particles directly in the volume of the gas mixture, i.e. the formation of soot, the presence of which in the structure of the material is unacceptable. In addition, the presence of hydrogen significantly affects the nature of the course of homogeneous heterogeneous processes of pyrocarbon formation, significantly limiting the homogeneous component of such processes and thereby increasing the contribution of heterogeneous proper, i.e. occurring directly on the entire inner surface of the reinforcing base, the processes of formation of pyrocarbon. Thereby, obtaining a nanostructured material with an average size of graphite-like fragments in its structure not exceeding 30 nm is achieved. An implant for replacing bone defects from a composite carbon nanomaterial containing a pyrocarbon matrix and a multidirectional reinforcing frame made of rods formed of carbon fibers located along the axis of the rods,

The implant proposed in this technical solution for the replacement of bone defects consists of a carbon composite nanostructured material containing a pyrocarbon matrix and a reinforcing framework of carbon fibers, namely a multidirectional framework of rods molded from carbon fibers located along the axis of the rods (Fig 4) . The implant material has an elastic modulus of not more than 15 GPa, open porosity of the material of at least 5% vol., And the average size of graphite-like fragments in the structure of the material does not exceed 30 nm. Due to the combination of a carbon fiber macrostructure with a nanostructure, the implant has high strength (more than 30 MPa in compression) and an elastic modulus (not more than 15 GPa) well balanced with the elastic modulus of the bone. The material of the implant has good biocompatibility. Implants can have various shapes and sizes, which are most suitable for a particular application depending on the shape and size of the defect, as well as on the type of disease and method of surgical treatment.

The proposed technical solution formulated the preferred options for the shape of the implants to replace bone defects. For example, one of the preferred forms of the implant is the shape of a cylinder (Fig 5). This form is close to the form of bone defects often encountered in practice - this is the form vertebrae, intervertebral discs, tubular bones of extremities since in many cases, coincides with the shape of the compensated bone defect.

In some cases, it is preferable that the upper base of the implant is not parallel to the lower base and has an angle of inclination of 4 - 40 ° (Fig 6). This form of implants is preferred, for example, when replacing the intervertebral discs of the lower lumbar and sacral spine. Thereby, the maximum filling of the defect is achieved. The upper and lower base of the implant are in contact with the upper and lower vertebrae, respectively, located in relation to the defect. When the implant is inserted into the defect, the contact of these implant surfaces with healthy bone tissue is ensured, which creates the supportability of the spinal column.

In certain cases of surgical intervention, a slightly modified cylindrical shape is more preferable, namely, the lateral surface of the implant is formed by a cylindrical surface and a plane formed by a cut off cylindrical segment (Fig 7). This form of implant is preferred, for example, when replacing bone defects of the vertebrae. In this case, when installing the implant in the spinal column, the cylindrical surface is oriented parallel to the front side of the vertebral column, coinciding in shape with the shape of the front surface of the vertebrae. Moreover, the flat side of the implant is oriented deep into the spinal column and provides, due to the space of the cut off cylindrical segment, free space for the location of the spinal canal. This ensures maximum filling of the bone defect without deforming the spinal canal. The upper and lower base of the implant in the form of circular segments are in contact with the upper and lower vertebrae located, respectively, with respect to the bone defect. When an implant is inserted into a bone defect, the contact of these implant surfaces with healthy bone tissue is ensured, which creates the supportability of the spinal column. In some cases, it is preferable that the upper base of such an implant is not parallel to the lower base and has an inclination angle of 4-40 ° (Fig 9). This form of implants is preferred when replacing defects in long tubular bones, for example, during an osteotomy operation. The size of the implant and the angle between the bases of the cylinder are selected based on the size of the defect. Preferably, the height of the cylindrical implant is 4 to 100 mm and the diameter of the base is 10 to 30 mm. These sizes are preferred by the anthropological features of the human skeleton and the most common cases of bone defect replacement. The implant may have one through hole (for example, Fig 6 and 8). The hole may have a cylindrical or elliptical shape. The hole can be used to place osteoconductive or osteoinductive materials in it, which accelerate the formation of bone tissue, fusion of the implant with bone tissue and the formation of a single bone-carbon block in the area of the replaced defect. Such materials may be calcium phosphates (hydroxyapatite, tricalcium phosphate), including those with collagen supplements or proteins that accelerate the formation of osteoblasts (bone growth factors), or fragments of the patient’s bone tissue (autobone), which can be taken during surgery or before her. In addition, prolonged-action drugs can be placed in this hole, providing a slow release of active drugs into the operated area in the postoperative period, which is especially important in the treatment of inflammatory diseases (bone tuberculosis, osteomyelitis).

The implant may have two blind holes. These holes can be used to accommodate osteoconductive or osteoinductive materials and drugs, as described above.

Preferably, the diameter of the holes is 0.1 to 0.5 of the diameter of the cylinder. If the diameter of the holes is less than 0.1 of the diameter of the cylinder, then such a hole is less convenient for accommodating the above substances. When the hole diameter is more than 0.5 of the cylinder diameter, the cross-sectional area of the implant is reduced, and, therefore, the compressive and bending strength of the implant is reduced, which is less preferred for a number of applications.

It is preferable that on the surfaces of the bases of the cylinder at the implant one or more grooves are made with a depth of 0.5 - 2 mm and a width of 1-3 mm (Fig 5). Such grooves increase the contact area of the implant surface with the bone tissues into which the implant is installed, and increase the strength of its fixation in the bone-carbon block formed after surgery. Due to the grooves, a stronger mechanical coupling of the implant with the bone tissue is ensured, both due to the friction forces during its installation, and due to the ingrowth of the newly formed bone in the grooves in the postoperative period. Before installing the implant in a bone defect or in the area of the intervertebral disc, the grooves can be filled with osteoinductive or osteoconductive material to accelerate the formation of a bone-carbon block in the implantation area. With a groove width of less than 1 mm and a depth of more than 2 mm, their dimensions are small and it is difficult to place the above substances in the grooves. Grooves with a width of more than 3 mm in some cases can lead to a significant decrease in implant strength, which is unacceptable. The formation of grooves with a depth of less than 0.5 mm is technically more difficult.

It is possible to use an implant, the volume of which is formed by three cylinders of different diameters having a common axis (Fig 8). The diameters of the outer cylinders are smaller than the diameter of the middle cylinder. This form of implants is optimal, for example, when replacing bone defects in the tubular bones of the limbs. In this case, when installing the implant in the defect zone, the cylindrical axis of the implant is oriented parallel to the axis of the tubular bone, and the diameter of the middle cylinder of the implant is close in shape and size to the tubular bone in the area of the replaced bone defect. In this case, the outer cylinders of the implant are installed deep into the inner channel of the tubular bone and provide fixation of the implant in the defect zone. This ensures maximum filling of the bone defect without significant deformation of the bone marrow canal. When an implant is inserted into a bone defect, these implant surfaces are in contact with healthy bone tissue, which creates a bearing capacity in the defect zone. Preferably, the diameter of the middle cylinder of the implant made in the form of three coaxial cylinders is 10-30 mm, the diameter of the extreme cylinders is 5-15 mm, the total length of the implant is 20-140 mm, and the length of the end cylinders of the implant is 5-20 mm.

Preferably, the implant in the form of three coaxial cylinders has a through hole or two blind holes, the axis of which coincides with the axis of the cylinders. Before installing the implant in the area of the replaced bone defect, the holes can be filled with osteoinductive or osteoconductive material to accelerate the formation of a bone-carbon block in the area of implantation or medicinal substances, providing, for example, the suppression of inflammatory processes in the field of implantation.

If holes are made in the implant, it is preferable that the diameter of the through hole or blind holes of the implant in the form of three coaxial cylinders is 0.3 to 0.5 of the diameter of the end cylinders. If the diameter of the holes is less than 0.3 of the diameter of the extreme cylinder, then such a hole is less convenient for accommodating the above substances. When the hole diameter is more than 0.5 of the cylinder diameter, the cross-sectional area of the implant is reduced, and, therefore, the compressive and bending strength of the implant is reduced, which is less preferred for a number of applications.

For a number of cases, it is preferable that the implant for the replacement of bone defects from composite carbon nanomaterial was made in the form of a prism (Fig. 10). This form of implant can be used, for example, to compensate for such bone defects of the vertebrae that partially affect the vertebral body. The base of the prism can be different, for example, L-shaped, U-shaped, in the form of a cross. Preferably, the length of the side of the base of the prism is 8-30 mm and the height of the prism is 4-100 mm.

If holes are made in the prism-shaped implant that can be filled with osteoinductive or osteoconductive material to accelerate the formation of the bone-carbon block in the implantation region or with drugs that, for example, suppress inflammatory processes in the implantation region, it is preferable that the diameter of the through hole or blind holes was 0.1 - 0.5 of the diameter of the extreme cylinder. If the diameter of the holes is less than 0.1 of the diameter of the outer cylinder, then such a hole is less convenient for accommodating the above substances. When the hole diameter is more than 0.5 of the diameter of the outer cylinder, the cross-sectional area of the implant is reduced, and, therefore, the compressive and bending strength of the implant is reduced, which is less preferred for a number of applications.

To increase osteoinduction, i.e. activation process, the formation of newly formed bones on the surface of the implant, it is preferable that the surface of the implant was covered with a layer of hydrocapatite. Surface coating may be carried out by various methods. For example, by spraying hydroxyapatite with known PVD spraying methods, precipitating hydroxyapatite from aqueous solutions of salts, and rubbing hydrosiapatite aqueous paste into macropores of the implant surface.

These preferred additional features can be combined in the implant in various combinations, and the implants themselves are used in vertebrology, inert limb surgery, maxillofacial surgery to replace various bone defects.

Implants are used, for example, as follows in the replacement of bone defects of the spine. Before use, the implants are sterilized. Sterilization of implants is carried out in the usual way, for example, in an autoclave. The shape and size of the implant is determined by the surgeon before surgery on the basis of an X-ray assessment of the size of the bone defect. During the operation, access to the affected spine and the radical phase of the operation are performed according to standard surgical techniques. After resection of the affected areas, the implant is installed. In the state of reclamation, the implant is tightly inserted into the bone defect. The position of the implant should correspond to the axis of the bone load. The implant provides reliable stabilization of the operated part of the bone. In the final part of the operation, the tissues over the plastic region are sutured with 2-3 catgut sutures. The wound is sutured in layers. Apply an aseptic dressing.

Brief Description of the Drawings

Fig 1. Mandrel for assembling a reinforcing base material.

Fig 2. A mandrel for assembling a reinforcing material base with vertical rods installed around the perimeter - guides and assembled with three layers of rods.

Fig 3. Frame assembled by layered assembly of rods with partially mounted vertical rods.

Fig 4. Material surface structure - horizontally and vertically located rods connected by a pyrocarbon matrix and macropores are visible. Fig 5. Implant option for replacing cylindrical bone defects with grooves on the bases.

Fig 6. Variant of a cylindrical implant with non-parallel bases. Fig 7. Variant of an implant to replace bone defects of a cylindrical shape with a cut off cylindrical segment.

Fig 8. Implant variant in the form of three coaxial cylinders.

Fig 9. Variant of a cylindrical implant with non-parallel bases with a cut off cylindrical segment. Fig 10. Variant of an implant for the replacement of bone defects of a prismatic shape.

The designations in the figures: H — implant height, D — implant diameter, B — implant width, d — hole diameter, L — linear dimension, and — plane angle.

An embodiment of the invention

For the manufacture of composite material using rods with a diameter of 1, 2 mm, molded from carbon fibers brand UKN-5K. The rods are made by pultrusion technology, which impregnates carbon fibers with a polymer binder - an aqueous solution of polyvinyl alcohol - to form a bundle, pulling the bundle through a die to obtain a rod cross section of 1.2 mm, heat treatment at 140 ° C to cure the binder.

The manufacture of a composite material begins with the formation of a fibrous reinforcing base, i.e. from assembling a framework of rods molded from carbon fibers. To do this, on the mandrel (Fig 1), rods are installed vertically around its perimeter in the holes, which will subsequently serve as guides when assembling the frame. In the horizontal plane on the mandrel, perpendicular to the guide rods, the rods are laid at a distance of 1.2 mm from each other, parallel to each other. The next (second) layer is formed on the first, laying the rods on the same distance from each other, parallel to each other, at an angle of 60 ° to the rods of the first layer. The next (third) layer is formed on the second, laying the rods at the same distance from each other, parallel to each other, at an angle of 60 ° to the rods of the second layer in a direction that does not coincide with the direction of the first layer. The fourth layer is also collected as the first, fifth layer - as the second, etc. The required frame height is obtained by stacking the desired number of layers. In the vertical channels of the frame formed after the assembly of the layers, vertical rods are installed.

The assembled frame is removed from the mandrel and a graphite heater is installed along its vertical axis. The resulting assembly is placed in the reaction chamber, installing the heater in the conductors. The chamber is filled with a reaction gas mixture. Voltage is supplied to the current leads and by passing current, the heater is heated to a temperature of 1100 ° C. In this case, a temperature gradient of 20 ° C / mm is realized in the frame. processing of the frame is carried out for 54 hours in a gaseous medium: methane - 75% vol., hydrogen - 25% vol. During processing, the temperature of the heater is increased so that the temperature gradient in the frame does not exceed 100 ° C / mm. After processing, the assembly is removed from the reaction chamber.

The result is a composite carbon nanomaterial in which the mass fraction of fibers is 32%, the average size of graphite-like fragments in the structure of the material is 11 nm, the modulus of elasticity of the material under compression is 12 GPa, the compressive strength is 82 MPa, and the density is 1.67 g / cm open porosity - 10% vol. The density of the material was determined by the hydrostatic method, porosity by water absorption, the elastic modulus and strength by test machines, and the average size of graphite-like fragments in the material structure was determined by X-ray diffraction analysis. The resulting material is well processed by traditional machining methods: drilling, milling, cutting. The material is used to make implants in the form of a cylinder 30 mm high and 20 mm in diameter and 7x3x3 mm in size.

The toxicological tests carried out (in accordance with GOST R ISO 10993-2009 and GOST R 52770-2007) showed that the change in pH of the aqueous extract (3 days, 37 ° C, the ratio of 10 g of material and 500 ml of water) compared with the control distilled water is 0.3 (permissible value of 1.0). The maximum value of the optical density of the aqueous extract in the UV region of the spectrum in the wavelength range of 230-360 nm is 0.1 (an acceptable value of 0.3). The content in the aqueous extract of formaldehyde is 0.01 mg / l, vinyl acetate is less than 0.05 mg / l (acceptable values are 0.1 and 0.2 mg / l, respectively). A toxicity study using an AT-05 toxicity analyzer using granulated bull sperm frozen in liquid nitrogen vapor showed a toxicity index of 94.2% (a valid value of 70-120%). Thus, the material is not toxic.

To determine the response of bone tissue to the implantation of a carbon composite material, surgical operations were performed on chinchilla rabbits weighing 2.9-3.1 kg using manufactured implants. Surgery consisted in exposure of the distal epimetaphysis of the femur, iliac crest, the formation of a standard defect of 7x3x3 mm in size and the introduction of a carbon nanostructured implant made according to the proposed technical solution. The implants were removed at periods of 1, 2, 3, 4 weeks and 3 months after the operation, the area of operation was examined. When the implants were removed at the indicated time, no inflammatory or osteolytic processes were detected. After 1 week, a small amount of hemorrhagic exudate was determined between the bone and the implant; by 2 weeks it was no longer detected. At 3 and 4 weeks, a thin layer of connective tissue appeared on the surface of the implant at the sites of contact with bone tissue.

During orthotopic implantation of carbon nanostructured implants, it was found that adverse changes from the tissues surrounding the implant and intraarticular formations were not observed in all periods of observation. From the end of the second week, the process of bone formation originating from the bone bed was noted. By 2 months, bone beams were closely laminated to the implant. Microscopy in reflected light of drug cuts in a period of 2 months recorded areas of bone tissue growth not only in the marginal sections of the implant, but also in its deeper cells. Luminescent microscopy of drug cuts within 1-2 months after the operation revealed a bright glow of the newly formed bone at the bone-implant border, and a glow also appeared inside the implant, indicating the growth of bone tissue not only in the marginal, but also in the deeper pores of the material. By 3 months, the implant was tightly surrounded by bone tissue. This indicates inertia. the implant was tightly surrounded by bone tissue. This indicates the inertness of the material, which does not interfere with the growth of bone tissue in and around the implants. The walls of the bone defect were sclerotic. Postoperative scar in the area of stitched muscles, fascia without inflammatory phenomena. Macroscopically enlarged lymph nodes (paraaortic) were not found.

By the end of 1 year, germination in the marginal sections of the implant of the newly formed bone was observed along the entire circumference of the implant. Micro roentgenograms with a direct increase in the frontal and sagittal sections showed the preservation of the natural orientation in the bone tissue and the smooth transition of the bone beams from the bed to the implant pores without a line of rupture or fracture.

Thus, experimental work on animals has shown that nanocarbon implants are firmly fixed in the animal’s bone bed, fixation stiffness is fully preserved throughout the entire observation period, and the implant’s strength does not decrease, and ossification sites are determined in its structure without any signs of material resorption . That is, the material obtained in its mechanical, toxic, osteoconductive properties fully complies with the requirements for materials used to replace bone defects.

Industrial applicability

The application of the present invention provides an implementation of a method of manufacturing a biocompatible porous carbon nanostructured composite material for replacing bone defects with elastic characteristics similar to those of bone and implants for replacing bone defects during operations to restore the functions of the human skeleton. The method is practically implemented and tested technically. It provides a composite material with the claimed properties and the manufacture of biocompatible implants to replace bone defects, testing of which confirms the claimed properties.

Claims

CLAIM

1. Composite carbon nanomaterial for the replacement of bone defects, including a pyrocarbon matrix and a fibrous reinforcing base, made in the form of a frame of rods containing carbon fibers oriented along the axis of the rods, and containing vertically mounted rods and horizontal layers, each of which is formed in parallel oriented rods and the rods of each layer are oriented relative to the rods of the previous and subsequent layer at an angle of 60 °, characterized in that the elastic modulus of nanom Therians not more than 15 GPa, a mass fraction of carbon fibers in the structure of the nanomaterial is 30-38%, an open porosity - not less than 5 vol%, and the average size of fragments in a graphite structure material less than 30 nm..

2. Composite carbon nanomaterial according to claim 1, characterized in that the diameter of the rods containing carbon fibers is 0.7-2 mm

3. Composite carbon nanomaterial according to claim 1, characterized in that its density is 1.2 - 1.8 g / cm.

4. A method of manufacturing a composite carbon nanomaterial for the replacement of bone defects, including the formation of a reinforcing base in the form of a frame layer-by-layer laying of rods formed of carbon fibers oriented along the axis of the rod, arranging the rods in each layer parallel to each other and at an angle of 60 ° with respect to the rods subsequent and previous layers, until the required number of layers is reached, with subsequent laying in the formed vertical channels of additional rods, and the subsequent is formed I matrix by the deposition of pyrocarbon from a gaseous medium containing at least one hydrocarbon at a temperature exceeding its decomposition temperature, characterized in that the gaseous medium additionally contains hydrogen in an amount of 2-45% vol., and the process of forming a carbon matrix is carried out at a temperature gradient inside the frame 10-100 ° C / mm.

5. The method according to claim 4, characterized in that the additional rods exceed the height of the stacked layers in length, and after installing the additional rods, the assembly of the carcass layers continues until the desired carcass height is reached.

6. An implant for replacing bone defects from a composite carbon nanomaterial containing a pyrocarbon matrix and a multidirectional reinforcing frame made of rods formed of carbon fibers located along the axis of the rods, characterized in that the implant material has an elastic modulus of not more than 15 GPa, mass fraction of carbon fibers in the structure of the nanomaterial is 30-38%, the open porosity of the nanomaterial is not less than 5% vol., and the average size of graphite fragments in the structure of the nanomaterial does not exceed 30 nm.

7. The implant according to claim 6, characterized in that it is made in the form of a cylinder.

8. The implant according to claim 6, characterized in that it is made in the form of a cylinder, the upper base of which is not parallel to the lower base and has an angle of inclination of 4-40 °.

9. The implant according to claim 6, characterized in that it is made in the form of a cylinder with a cylindrical segment cut off parallel to the cylindrical axis, while the volume of the cut off segment is less than 40% of the volume of the cylinder.

10. The implant according to claim 6, characterized in that it is made in the form of a cylinder, the upper base of which is not parallel to the lower base and has an inclination angle of 4-40 °, with a cylindrical segment cut off parallel to the cylindrical axis, while the volume of the cut off segment is less than 40 % of the cylinder volume.

11. The implant according to any one of p. 7 to 10, characterized in that the height of the cylinder is 4 to 100 mm, and the diameter of the base is 10 to 30 mm.

12. The implant according to any one of p. 7 to 10, characterized in that it has a through hole parallel to the axis of the cylinder, the diameter of which is 0.1-0.5 of the diameter of the cylinder.

13. The implant according to any one of p. 7 to 10, characterized in that it has two coaxial blind holes parallel to the axis of the cylinder, the diameters of which are 0.1-0.5 of the diameter of the cylinder.

14. The implant according to any one of p. 7-10, characterized in that on the surfaces of the bases of the cylinder made one or more grooves with a depth of 0.5 to 2 mm and a width of 1-3 mm

15. The implant according to claim 6, characterized in that it is made in the form of three coaxial cylinders, while the diameters of the outer cylinders are the same and less than the diameter of the middle cylinder.

16. The implant according to clause 15, characterized in that it has a through hole or two blind holes, the axis of which coincides with the axis of the cylinders, and the diameter of the through hole or blind holes is 0.3 - 0.5 of the diameter of the outer cylinders.

17. The implant according to any one of claims 15 to 16, characterized in that the diameter of the middle cylinder is 10-30 mm, the diameter of the outer cylinders is 5-15 mm, the total length of the implant is 20-140 mm, and the length of the extreme cylinder is 5- 20 mm.

18. The implant according to claim 6, characterized in that it is made in the form of a prism.

19. The implant according to claim 6, characterized in that the implant surface is completely or partially covered with a layer of hydroxyapatite.