Endoprosthesis for replacement of bone defects and pathologies and manufacturing method thereof

Abstract

The invention relates to medicine and concerns an endoprosthesis for replacing bone defects and a manufacturing method thereof. The endoprosthesis is made of carbon composite consisting of electrochemically treated carbon fabric, thermoplastic polymer and radiopaque filler layers and formed by hot molding followed by mechanical processing. In this case, the outer parts of the endoprosthesis consist of preformed alternating carbon fabric and thermoplastic polymer layers, and the inner part consists of preformed thermoplastic polymer layers and at least one radiopaque filler layer located therebetween them with the following ratio of components in the endoprosthesis, % by weight: carbon fabric - 68.7 to 69.1; radiopaque filler - 0.5 to 0.9; thermoplastic polymer - up to 100. The invention allows creating a biologically compatible, radiopaque endoprosthesis being toxically and carcinogenically safe for humans and having improved strength features and wear resistance and a longer service life, which can be used to eliminate bone pathologies and defects.

Description

[0001] ENDOPROSTHESIS FOR REPLACEMENT OF BONE DEFECTS AND PATHOLOGIES AND MANUFACTURING METHOD THEREOF

[0002] Field of the invention

[0003] The invention relates to medicine, namely traumatology, reconstructive surgery, endoprosthetics, orthopedics, and can be used to eliminate bone pathologies and defects, in particular, the hip joint, intervertebral discs, temporomandibular, knee, elbow and other joints, as well as to make plates and screws for osteosynthesis, due to the use of endoprostheses based on a radiopaque carbon material.

[0004] Prior art

[0005] Endoprostheses made from carbon materials have a number of advantages over metal, ceramic and polymer endoprostheses and are free from many of their disadvantages due to the fact that carbon materials are characterized by high biological compatibility, lack of toxicity and carcinogenicity, as well as lack of corrosion and stress fatigue (P. I. Zolkin and V. S. Ostrovskiy, “Carbon materials in medicine”, Moscow: Metallurgizdat, 2014, 144 pages with drawings). However, the manufacturability of carbon allows one to vary the physical and mechanical properties of carbon materials over a wide range, achieving optimal characteristics. Some carbon fiber plastics have strength characteristics (in particular, elastic modulus), structure (porosity), and electrochemical potential that are as close as possible to the similar characteristics of bone tissue, which increases the normal functioning of endoprostheses, eliminates the need for repeated surgery and improves the quality of life of patients.

[0006] Surgery widely uses a group of carbon composites, which are prepared by hot molding into a mold stack from layers of carbon fabric as a filler and polyamide or polypropylene film as a binder. The disadvantage of these materials is their radiolucency, and, as a consequence, the lack of visualization of the carbon material on control radiographs and tomographic studies, which makes it difficult to identify possible displacements and deformations of the installed implant in the postoperative period.

[0007] The patent literature discloses numerous solutions related to the use of carbon composites for replacing bone defects.

[0008] US 5,981,827 discloses a prosthetic product based on a carbon composite, which comprises a porous structural element formed by carbon fiber with a porosity of less than 200 microns and further comprises a filler to reduce the diameter of the pores, as well as a thin coating of diamond-like carbon on the outer surface of the composite, wherein the prosthesis is characterized by a density gradient with the highest density at the center of the composite product and the lowest density near the surface of the specified composite and / or high density at one end of the composite product and low density at the other end.

[0009] The disadvantage of the proposed technical solution is the use of a rather expensive coating of diamond-like carbon, as well as the radiolucency of the carbon material.

[0010] RU 2669352 discloses an implant for replacing bone defects made of a carbon composite comprising a porous matrix of crystalline carbon fibers with an interlayer distance of 3.58 to 3.62 A with a total fiber content of 20 to 80%. The filler material comprises 50 to 70% of crystalline carbon with an interlayer distance of 3.42 to 3.44 A and 10 to 20% of amorphous carbon in the coke form in the total pore volume of the matrix. In this case, carbon nanotubes are introduced into amorphous carbon in an amount of 0.05 to 1% by weight of amorphous carbon.

[0011] The disadvantage of this invention is the impossibility of preoperative modification of the implant taking into account the anatomical characteristics of the patient. Furthermore, according to the International Agency for Research on Cancer (IARC), carbon nanotubes should be classified as carcinogenicity group 2B (“possibly carcinogenic to humans”). In addition to the general toxic effect on the body, according to a number of studies, carbon nanotubes can selectively damage the genetic apparatus of cells and target organs remote from the site of introduction into the body. RU 2609829 discloses a composite for replacing bone defects and a manufacturing method thereof, comprising a fibrous reinforcing base made as a frame made of rods based on carbon fibers oriented along the axes of the rods, and comprising vertically installed rods and horizontal layers, each formed by parallel oriented rods, wherein the rods of each layer are oriented relative to the rods of the previous and subsequent layers at an angle of 60°, and a polycarbon matrix, while some pre-selected rods, several or all directions of reinforcement, which are part of the reinforcing base, comprise one or more chemical compounds from the group of alumina, silicon carbide, calcium orthophosphate, calcium pyrophosphate, titania, titanium carbide, zirconia, zirconium carbide, niobia, niobium carbide, hafnia, hafnium carbide, tantala, tungsten carbide making 0.1 to 10% by weight of the rod.

[0012] The disadvantage of the proposed technical solution is the complex design, the lack of osteoconstructive and osteoinductive potential in the described composite, as well as the composition comprising numerous chemical compounds that have not been sufficiently studied regarding the invasive use for humans and may have carcinogenic and pathogenic effects, for example, identified various pathological effects of titania on the human and animal body: oncogenic, immunomodulatory and allergic (N. S. Alyakhanovich and D. K. Novikov, “Prevalence, use and pathological effects of titania”, Bulletin of the Vitebsk State Medical Institute, 2016).

[0013] The closest prior art of the invention is a radiopaque carbon composite for eliminating bone defects according to patent RU 2749024. This composite consists of layers of carbon fabric and polyamide film, and further comprises one or more layers of basalt fibrous material as a radiopaque component, in a weight ratio of: carbon fabric 57.5 to 64.0%, basalt fibrous material 1.0 to 6.0%, and polyamide film to 100%.

[0014] The disadvantage of this technical solution is that the formation of the final product using the specified carbon composite is a rather material-intensive process due to the high level of waste during mechanical processing of the latter, for example, when it is necessary to cut small- sized implants from preformed mold stacks, which, in turn, negatively affects the cost of the finished product and the profitability of the production process. Furthermore, the use of basalt fiber gives the carbon composite radiopaque properties close to the radiopacity of bone, which leads to the merging of the image of the bone and endoprosthesis based on the composite on radiographic and tomographic images of the patient and thus makes it impossible to monitor the degree of survival of the endoprosthesis and control the likely occurrence of microcracks or other defects in the structure of the endoprosthesis itself.

[0015] Summary

[0016] The basic objective of the invention is creating a biologically compatible, toxically and carcinogenically safe human endoprosthesis with improved strength features and wear resistance and a longer service life that allows achieving a technical effect, which is higher productivity of the finished product due to low material loss (production waste) and the possibility of forming an endoprosthesis of any shape and size without negatively affecting the process performance and productivity as a whole.

[0017] The problem is solved by the fact that the endoprosthesis for replacing bone defects is made of carbon composite, and the outer parts of the composite consist of sheets formed by hot molding of three layers of electrochemically treated carbon tissue and alternating layers of thermoplastic polymer, and the inner part of the composite consists of hot-molded sheets of three layers of electrochemically treated carbon fabric, layers of thermoplastic polymer and at least one layer of radiopaque filler, which is located between the middle layer of carbon fabric and one of the adjacent layers of thermoplastic polymer subject to the following ratio of components, % by weight: carbon fabric - 68.7 to 69.1; radiopaque filler - 0.5 to 0.9; thermoplastic polymer - up to 100.

[0018] The endoprosthesis may comprise barium sulfate powder as a radiopaque filler. Furthermore, the outer parts of the endoprosthesis preferably comprise an osteoconductive substance introduced into the surface layer formed by carbon fabric and thermoplastic polymer. Calcium hydroxyapatite can be used as an osteoconductive substance.

[0019] In the second aspect, a method for manufacturing an endoprosthesis for replacing bone defects is proposed, which comprises performing two types of composite sheets at a temperature of 120 to 140°C and a pressure of 80 to 100 kg / cm2, wherein first-type sheets comprising thermoplastic polymer layers, which alternate with three electrochemically treated carbon fabric layers, and second-type sheets comprising thermoplastic polymer layers, which alternate with three electrochemically treated carbon fabric layers, and a radiopaque filler layer located between the carbon fabric layer and one of the adjacent thermoplastic polymer layers, and the thermoplastic polymer is laid on both sides of the carbon fabric, and the preformed sheets are laid layer by layer in a mold having the shape and size of the final endoprosthesis, molded and cooled under pressure, whereas the sheets of the first type are laid at least as the bottom and top layers, and the sheets of the second type are laid as the inner layer, subject to the following ratio components, % by weight: carbon fabric - 68.7 to 69.1; radiopaque filler - 0.5 to 0.9; thermoplastic polymer - up to 100.

[0020] The thickness of each preformed composite sheet preferably does not exceed 1 mm.

[0021] Barium sulfate powder can be used as a radiopaque filler.

[0022] The outer part of the upper and lower sheets is coated with calcium hydroxyapatite used as an osteoconductive coating.

[0023] Electrochemical pretreatment (ECPT) of carbon fabric allows increasing the porosity of the constituent carbon fibers so that the finished carbon composite based thereon is characterized by the pore size distribution, which is close as possible to that of the bone structure, which contributes to high biological compatibility and service life of the prosthesis and can be used for the manufacture of a stem for endoprosthetic hips, knees, elbow joints, and intervertebral discs. Furthermore, electrochemical treatment of carbon fabric promotes its better adhesion to a thermoplastic polymer, while the physical and mechanical properties of the resulting composite are improved.

[0024] Alternating layers of electrochemically treated carbon fabric, which is characterized by high biological compatibility, lack of toxicity and carcinogenicity, as well as lack of susceptibility to corrosion and fatigue stress, with layers of thermoplastic polymer, which, due to its adhesive properties when heated (for example, during hot molding), has the ability to be easily transformed into various forms allows creating a universal endoprosthesis of any shape, which is characterized by all the properties inherent in the components from which it is made, and the addition of a radiopaque filler gives it radiopaque properties.

[0025] Meanwhile, it was experimentally found that it is the specified ratio of components in the endoprosthesis that is optimal for achieving the best performance features (strength, wear resistance, biological compatibility) of the finished product while maintaining a sufficient level of thermoplastic properties required for more precise formation of the finished product. We conducted a series of experiments to vary the carbon fabric and thermoplastic polymer contents in the composite. The carbon fabric content was varied by varying the weight or number of the thermoplastic polymer layers, or by varying the fabric weight itself to achieve its proportion in the composite. Thus, a composite was produced with a carbon fabric content that varied from 69.1 to 75% with a radiopaque filler content of 0.5 to 0.9% and, accordingly, a reduced content of thermoplastic polymer. It was found that a shift in the ratio of components in the composite towards a higher carbon fabric content and, accordingly, a lower thermoplastic polymer content, which plays the role of a binder, leads to a more complex process of forming the finished product due to insufficient adhesion of the layers to each other and their delamination at the stage of forming the composite structure, which, when using a ready-made endoprosthesis, can lead to the occurrence of defects and deformation changes in the structure. A higher carbon fabric content in the composite structure also increases the endoprosthesis rigidity, which can cause stress at the site of attachment of the endoprosthesis in the bone and damage to the latter.

[0026] In the course of our research, we also produced a composite with a lower carbon fabric content ranging from 61.0 to 69.0%, a higher thermoplastic polymer content, and a radiopaque filler content ranging from 0.5 to 0.9%. It was found that a lower carbon fabric content in the composite along with a higher thermoplastic polymer content leads to the formation of an endoprosthesis with insufficient strength and durability features and complicates the composite forming process due to the leakage of molten thermoplastic polymer outside the carbon fabric at high temperatures during the thermoforming process and uneven distribution thereof between the deformation layers of the finished product.

[0027] The thermoplastic polymer used linear polyimide films, which are strong, resist to deformation, durable and having higher terminological wear resistance, physiological compatibility and biological safety. These films are produced by pre-drying linear polyamide acid in dimethyl formamide or dimethyl acetamide at 80 to 120°C on a drum-type substrate for 5 to 15 minutes until the residual solvent content is 20 to30%. Meanwhile, varying the drum rotation speed allows producing films of any thickness and weight.

[0028] We further carried out a series of studies to determine the optimal location of the radiopaque filler layer in the endoprosthesis structure and showed that its location between preformed layers of carbon fabric and thermoplastic polymer in the inner part of the endoprosthesis gives the latter optimal radiopaque properties and allows visualization thereof and obtaining high-quality radiographic and tomographic images with minimal risk of artifacts. Our studies demonstrated that placing a radiopaque component between layers of carbon fabric and thermoplastic polymer in one of the outer parts of the endoprosthesis is irrational and leads to distortion of the radiographic images, the appearance of artifacts, excessively high or, conversely, insufficient contrast of the resulting radiographic image. As a result of these studies, we further found that the optimal amount of the radiopaque component that provides its uniform distribution between the carbon fabric and thermoplastic polymer layers and allows obtaining radiographic images of high quality and level of detail is 0.5 to 0.9% by weight. A higher radiopaque component content of 1 to 1.5% by weight caused a deterioration in its uniform distribution between the endoprosthesis layers and a significantly poorer quality of radiographic images due to darkening, whereas a lower radiopaque component content of 0.3 to 0.45% by weight did not provide a sufficient endoprosthesis visualization level due to the fact that the obtained radiographic images were characterized by the appearance of weakly colored areas.

[0029] Moreover, in one of the embodiments of the invention, radiopaque filler uses barium sulfate powder, which, due to its low solubility in water, is a non-toxic substance for a human, unlike all soluble barium salts, which allows using it as a radiopaque substance. It is known that barium sulfate is often used as a radiopaque agent in radiographic studies of the gastrointestinal tract, since heavy barium atoms absorb X-rays well, unlike metal powders, when used as an additional radiopaque layer, barium sulfate powder is evenly distributed throughout the entire volume of the endoprosthesis in the interior thereof between the preformed carbon fabric and thermoplastic polymer layers, provides high quality radiographic and tomographic images of products with a visualization density of 950 to 1100 Hounsfield units, and, what is especially important, allows accurately visualizing the endoprosthesis in the bone structure (in these images, the endoprosthesis and the bone do not merge each other) and, accordingly, monitoring the endoprosthesis service condition in a human body and detecting the appearance of any defects or microcracks in the structure. It should be noted that, without deviating from the principles of this invention, the radiopaque filler may use any other material, for example, tantalum thread, which is characterized by high biological compatibility, but is inferior to barium sulfate powder in terms of the uniform distribution between the carbon fabric and thermoplastic polymer layers and a more labor-intensive process, since it requires additional effort for even placement between the said layers.

[0030] In accordance with one exemplary embodiment of the invention, the external parts of the endoprosthesis comprise an osteoconductive substance introduced into their surface layer formed by carbon fabric and a thermoplastic polymer in order to increase the biological compatibility of the endoprosthesis with the biological system of the human body.

[0031] Moreover, according to one exemplary embodiment of the invention, the osteoconductive substance uses calcium hydroxyapatite, which has acquired enormous importance in medicine due to its incredible properties. Thus, being the main inorganic component of the bone and dental tissues of the body, calcium hydroxyapatite has an identical chemical composition and, accordingly, physical and mechanical properties and unique biological compatibility with bone tissue, on which basis it is widely used in orthopedics, surgery, and traumatology. An addition of calcium hydroxyapatite into the surface layer of the outer parts of the endoprosthesis promotes the penetration of elements such as calcium and phosphorus to the site of bone tissue formation, whereby the reflection effect of the endoprosthesis during surgery is reduced, and its consolidation with the musculoskeletal tissue is accelerated and the microcapillary resource of tissues increases.

[0032] As noted above, it is this ratio of the endoprosthesis components that is optimal for achieving the best performance features (strength, wear resistance, biological compatibility, radiopacity) of the finished product while maintaining a sufficient level of thermoplastic properties and the necessary easy molding of the finished product. Furthermore, the biomechanics of the proposed radiopaque carbon composite showed good resistance to loads in the absence of structural changes in the prototypes.

[0033] Thus, the proposed method for forming an endoprosthesis by hot molding a mold material consisting of layer-by-layer laid out carbon fabric and impregnated with polymer by infusion allows producing an endoprosthesis of any thickness and shape without a negative impact on its performance features and with a minimum amount of waste, which significantly increases the process productivity and simplicity of the finished product.

[0034] Meanwhile, the thickness of each preformed composite sheet does not exceed 1 mm, whereby it is easily machined, which allows cutting out the required product outline according to a template with a minimum amount of material waste, followed by placing such sheets in a mold and forming the final products requiring minimal mechanical processing. The number of sheets of the mold stack is determined by the required dimensions and thickness of the finished product, and the material loss of this production method does not exceed 10%. The use of preformed sheets for manufacturing a carbon composite can also significantly reduce the overall molding time of one part to allow simple machining and thus significantly reducing the production cost thereof. In one of the embodiments of the invention, barium sulfate powder was used as a radiopaque filler evenly distributed between the middle layer of carbon fabric and one of the adjacent thermoplastic polymer layers in the inner layer of the endoprosthesis, although a tantalum thread or any other radiopaque component could also be used component, without departing from the principles of this invention.

[0035] An osteoconductive substance is applied to the outer part of the upper and lower sheets in order to improve the biocompatibility of the endoprosthesis with the biological system of the human body.

[0036] In this case, calcium hydroxyapatite is used as an osteoconductive substance, which in the form of a powder or solution is applied with a brush to the outer parts of the upper and lower sheets of the composite, which are electrochemically pretreated carbon fabric layers in an amount of 10% by weight of the layer. The amount of calcium hydroxyapatite powder is determined experimentally and is sufficiently uniform to distribute it on the surface to be coated. In this case, due to the electrochemical pretreatment, the carbon fabric layers that form the outer parts of the upper and lower sheets of the composite acquire a porous structure, which facilitates the penetration of calcium hydroxyapatite powder into the surface pores of the carbon fabric, which, in turn, allows increasing the degree of fixation of the osteoconductive coating in the surface layers of the endoprosthesis and minimize its losses when using the finished product.

[0037] Embodiments of the invention

[0038] The invention is implemented in several embodiments according to the examples below of manufacturing an endoprosthesis based on carbon composite.

[0039] Example 1

[0040] The electrochemically treated carbon fabric and thermoplastic polymer are cut into rectangles measuring 200 x 250 mm. The electrochemical pretreatment of carbon fabric is carried out in an aqueous solution of potassium iodide with a concentration of 0.08 to 0.1 g / 1 with the addition of 0.1 ml / 1 of an alcohol solution of iodine with a concentration of 0.04 to 0.08 g / 1 and NH4OH until a neutral environment is obtained, for 15-30 minutes at a voltage of 70 to 80 V and a current density of 5.5 to 7.5 A / m2. The electrochemical treatment of carbon fabric promotes better adhesion to the binder polyamide film, while improving the physical and mechanical properties of the resulting composite.

[0041] Thus formed first-type sheets (1 mm thick) consist of six thermoplastic polymer layers, which alternate with three carbon fabric layers. The further formed large stacks consist of the first-type sheets with separating layers of antiadhesive film therebetween, whereas every three or four sheets within the stack are provided with a 0.5 mm metal sheet to transmit pressure. Separately, to provide radiopacity, second-type sheets are formed, wherein a layer of barium sulfate powder with a particle size of 0.06 mm is brushed into the middle layer between the carbon fabric and the thermoplastic polymer. The upper first-type sheets of carbon composite are formed separately. Calcium hydroxyapatite powder is applied to the top layer of the electrochemically pretreated carbon fabric in an amount by weight of less than or 10% of the weight of one layer of carbon fabric. The sheets of the said types prepared in this way are subjected to hot molding at 120 to 140°C and 80 to 100 kg / cm2for 30 minutes and cooled under pressure to 60°C, then removed and separated. From each molded 1 mm sheet, the outline of the required product is cut out according to a template before the sheets are placed in a mold having the shape and size of the final endoprosthetic product and further molded at 300 to 350°C and at least 100 kg / cm2for at least 30 minutes and cooled under pressure. In this case, sheets with an outer coating of calcium hydroxyapatite are laid on the top and bottom layers, and a second-type sheet is laid on the middle inner layer, which ensures the radiopacity of the material. The number of sheets of the mold stack is determined by the final specific type of finished product and usually ranges from 10 to 15. In this production method, the material losses do not exceed 10%, and the resulting endoprosthesis produced by this method requires minimal mechanical processing.

[0042] Table 1 shows the physical and mechanical properties of the resulting composite.

[0043] Table 1

[0044] Example 2

[0045] The method of manufacturing an endoprosthesis based on carbon composite according to this example involves carrying out all the stages described in Example 1, with the exception that when forming the second-type sheets to ensure radiopacity, a tantalum thread pattern is laid out in the middle layer between the carbon fabric and the thermoplastic polymer instead of barium sulfate powder.

[0046] The developed carbon composite can serve as the basis for various types of bone-frame materials, which will primarily be found in emergency traumatology and rehabilitation medicine, as well as in veterinary medicine. Further, the endoprosthesis, which parts consist of preformed sheets of the specified types of carbon composite layers, are characterized by high biocompatibility with tissues along with the rapid restoration of the surrounding structure of the organs of the postoperative field, as well as high similarity in physical and chemical properties, namely elastic modulus and porosity with the bone tissue.

[0047] Thus, the proposed invention allows creating a biologically compatible, radiopaque endoprosthesis that is toxically and carcinogenically safe for humans, having improved strength features and wear resistance and longer service life, as well as significantly increasing the productivity of the endoprosthesis production process due to low material losses, and providing any shape without negatively affecting the performance features and process productivity as a whole.

Claims

CLAIMS1. An endoprosthesis for replacing bone defects, which is made of carbon composite, wherein the outer parts of the composite consist of sheets formed by hot molding of three electrochemically treated carbon fabric layers and alternating thermoplastic polymer layers, wherein the inner part of the composite comprises hot molded sheets of three electrochemically treated carbon fabric layers, thermoplastic polymer layers, and at least one radiopaque filler layer, which is located between the middle carbon fabric layer and one of the adjacent thermoplastic polymer layers, subject to the following ratio of components, % by weight: carbon fabric - 68.7 to 69.1; radiopaque filler - 0.5 to 0.9; thermoplastic polymer - up to 100.

2. The endoprosthesis according to claim 1, wherein barium sulfate powder is used as a radiopaque filler.

3. The endoprosthesis according to claim 1 or 2, wherein the outer parts comprise an osteoconductive substance introduced into the surface layer formed by carbon fabric and a thermoplastic polymer.

4. The endoprosthesis according to claim 3, wherein calcium hydroxyapatite is used as an osteoconductive substance.

5. A method of manufacturing an endoprosthesis for replacing bone defects according to any one of claims 1 to 4, comprising preforming of two types of composite sheets at a temperature 120 to 140°C and a pressure 80 to 100 kg / cm2, wherein first-type sheets comprising thermoplastic polymer layers and alternating three electrochemically treated carbon fabric layers, and second-type sheets comprising thermoplastic polymer layers and alternating three electrochemically treated carbon fabric layers and a radiopaque filler layer located between the carbon fabric layer and one of the adjacent thermoplastic polymer layers, wherein the thermoplastic polymer is laid on both sides of the carbon fabric, and the preformed sheets arelaid layer by layer in a mold having the shape and size of the final endoprosthesis and are molded and cooled under pressure, while the first-type sheets are laid at least as the bottom and top layers, and the second-type sheets are laid as the inner layer, subject to the following ratio of components, % by weight: carbon fabric - 68.7 to 69.1; radiopaque filler - 0.5 to 0.9; thermoplastic polymer - up to 100.

6. The method according to claim 5, wherein the preformed sheets are molded at 300 to 350°C and at least 100 kg / cm2for at least 30 minutes.

7. The method according to claim 5 or 6, wherein the thickness of each sheet of preformed composite is preferably not greater than 1 mm.

8. The method according to claim 5 or 6, in which barium sulfate powder is used as a radiopaque filler.

9. The method according to any one of claims 5 to 8, wherein an osteoconductive coating is applied to the outer surface of the top and bottom sheets.

10. The method according to claim 9, wherein calcium hydroxyapatite is used as an osteoconductive substance.

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