RU2479319C1 - Silicon-doped calcium phosphate bioceramics (sbc) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, particularly to formulation of porous bioglassceramics containing fine soluble potassium, synthetic mineral granules - calcium phosphates that are parts of native bone tissue, wollastonite formed by crystallisation of soluble potassium, as well as addition of carbonate and carbon pore-former. The invention also refers to a method for making medical implant materials and devices of the presented formulation suitable for replacement of bone defects and deformities in maxillofacial surgery, dental surgery, neurosurgery, traumatology and orthopaedics.

EFFECT: bioceramics is gradually replaced by bone tissue and consists of the ingredients having no toxic, allergic, carcinogenic and mutagenic effects on human body.

3 cl, 2 tbl, 4 ex

Description

The invention relates to medicine, namely to the composition of a biocomposite material, a method for its manufacture, and can be used for the manufacture of implant materials and products intended to replace and eliminate defects and deformations in reconstructive and osteoplastic surgery.

Recently, bioactive composite materials have been proposed for clinical use that successfully compete with metals and alloys, oxide ceramics, polymers and carbon-based materials. Of particular interest are porous osteoconductive materials, including calcium phosphate bioglassceramic materials, which contribute to the attachment, proliferation and differentiation of bone cells into osteoblasts with subsequent appositional formation of new bone tissue on their surface. A characteristic feature of these materials is that they are not subject to encapsulation by the body. In this case, bone tissue, growing into the implant, is able to form a biochemical bond with it. Such a reaction of the body to the implantation of bioactive inorganic calcium phosphate materials is explained by the proximity of their mineral composition and pore structure to the native bone [Nikitin AA, Zausova OV, Titova NV, Shapovalov AB, Vlasova EB , Popova L.A. The use of biocompatible calcium-phosphate glass ceramics “BCS” in the surgical treatment of jaw cysts // Glass and Ceramics. - 2007. - No. 10. - S. 37-38].

The possibility of using calcium phosphate materials to replace defects and eliminate deformations of various bone tissues has been clinically proven [Solunin VL, Shapovalov AB, Vlasova EB, Topilina LA, Nikitin AA, Nikitin D.A. ., Kedrov A.V. New domestic implant materials and their application in clinical practice // Glass and Ceramics. - 2010. - No. 12. - S.27-30].

The disadvantage of calcium phosphate bioglassceramics is a significant content (more than 50 wt.%) Of glass phase, which leads to low resorbability and brittleness of the implant material. The fragility of the material complicates its mechanical turning during fitting to the bone bed, and also causes difficulties in fixing the implant to the bone [Kosyakov M.N. Clinical and experimental rationale for the use of apatitosilicate implants to replace defects and deformations of the bones of the facial skull: dis. Candidate of Medical Science - M., 2002, 121 p.].

Closest to the proposed invention is a material for bone implants based on medical glass and hydroxyapatite and a method of manufacturing this material (patent RU 2053737 - prototype).

Numerous clinical observations have established the disadvantages of this prototype, which consist in the fact that the bone can grow into the pores of the implant only to a small depth, forming an insufficiently strong surface connection with the implant. In addition, even with prolonged contact with the internal environment of the body, the implant does not undergo resorption and replacement with bone tissue.

The aim of the invention is the creation of osteoconductive bioceramics of silicocalcium phosphate ("BCS"), gradually replaced by bone tissue, and a method of manufacturing implant materials and products on its basis to eliminate defects and deformations in reconstructive and bone plastic surgery.

The goal is solved by the fact that the composite material consists of biocompatible bioresistive and bioresorbable components that do not have a general toxic, allergic, carcinogenic and mutagenic effect on the human body and a well-developed homogeneous pore structure, which also ensures the effectiveness of the clinical application of this development in these areas of medicine.

The composition of the biocomposite material "BCS" includes the following components:

- a bioresistive glassy sodium silicate matrix, providing a uniform distribution of mineral phases (bioactive and hardening), pore formers and pores of different sizes and shapes;

- bioresorbable bioactive phase, consisting of calcium phosphates of hydroxyapatite (HA) Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ and more resorbable β-tricalcium phosphate (β-TCP) β-Ca ₃ (PO ₄ ) ₂ , providing a prolonged process of osteogenesis in implant material;

- hardening mineral phase (wollastonite CaSiO ₃ ) formed during crystallization of the glassy matrix as a result of its heat treatment;

- pore formers of organic and inorganic origin, which are administered separately, namely: pre-diluted starch in distilled water, which is mixed with HA or β-TCP powder to obtain porous granules, while calcium carbonate CaCO _{3 is} mixed with a glassy matrix powder for the formation of the porous structure of the biocomposite material;

- interpenetrating pores with a bimodal distribution in size and shape, namely spherical with a diameter of less than 50 to 100 microns to ensure the adsorption of proteins and adhesion of osteogenic cells, as well as channel diameters of 100 to 200 microns or more for vascularization of blood vessels and colonization of bone cells of the entire volume the implant.

The developed method for manufacturing the implantation material “BCS” with a predominantly open cellular-channel pore structure allows us to attribute it to the number of osteoconductive, osteoconductive, providing optimal conditions for attachment, proliferation and differentiation of cells into osteoblasts with subsequent appositional formation of bone on the surface and in the volume of the implant.

The temperature-time regime of sintering bioceramics "BCS" provides a mineral composition and bimodal pores, the distribution of which in the structure of the material is carried out in the following limits:

- spherical pores with a diameter of less than 50 microns and from 50 to 100 microns are 45-55% and 20-25%, respectively;

- channel pores with a diameter of 100 to 200 microns and more than 200 microns are 10-5% and 8-10%, respectively.

The change in the pore structure and properties of the material is governed by the relations between the mineral phases and the glassy matrix, the content of which varies within the following limits:

- Mineral phases not less than 65 wt.% - Vitreous matrix no more than 35 wt.% - open porosity from 60 to 70% - water absorption not less than 65% - Hydrogen indicator from 6 to 9

As the vitreous sodium silicate matrix, medical glasses are used in the present invention. In particular, medical container glass of the MTO brand with the content of oxides (wt.%) Can be used: 73.0 ± 0.50 SiO ₂ , 2.5 ± 0.20 Al ₂ O ₃ , 2.0 ± 0.30 MgO , 8.0 ± 0.30 CaO, 14.5 ± 0.25 Na ₂ O. The use of MTO glass provides the formation of a porous skeleton, on the surface and inside of which there are minerals phosphates and calcium silicates. It was experimentally proved that silanol groups (≡Si-OH) present in this matrix increase the tendency of the material to remineralize bone HA after implantation.

The hydrophilicity characteristic of sodium silicate glasses contributes to the rapid wetting and impregnation of the entire volume of the implant with tissue fluid, as well as, if necessary, drugs (antibiotics, antiseptics and other drugs).

The introduction of pore formers in the amount of 0.1 to 10 wt.% Provides an implant material with a well-developed homogeneous, mainly open pore structure, which favors the process of osteogenesis.

The change in the pore structure and material properties is also achieved by selecting the fractional composition of the bioactive phase and the vitreous matrix, based on the condition that their volume content varies from 1: 1 to 4: 1, depending on the case of clinical application.

The manufacturing process of bioceramics "BCS" includes the following stages.

Grinding of sodium silicate glass to obtain a glass powder with a specific surface area of 1.2 to 2.4 m ² / g. The particle size of the glassy matrix in this case is from 2 to 1 μm. A carbonate-containing pore former with a specific surface of 2.5 to 3.0 m ² / g, which corresponds to a particle size of 0.9 to 0.7 μm, is added, and both components are thoroughly mixed until a homogeneous mixture is obtained.

Granulation of the bioactive phase is carried out by adding a binder, which can be polyvinyl alcohol, collagen or starch. The presence of one of these components provides granules with a specific surface area of from 0.01 to 0.2 m ² / g, and their size varies from 1000 to 100 microns.

The amounts of the bioactive phase and the vitreous matrix calculated in accordance with the given composition are mixed in a mill with corundum beakers, the rotation speed of which is 50-100 rpm, for 3-10 minutes.

The prepared mixture is placed in sectional metal molds, which are placed in a laboratory electric furnace. The furnace is heated in accordance with the temperature-time mode of sintering according to a given program. The rate of rise and decrease in temperature is regulated by zones, providing the formation of a predominantly open pore structure. The sintering process of implant materials includes the following areas:

- heating for 60 minutes at temperatures up to 600 ° C with a speed of 8-10 ° C / min;

- sintering for 40 minutes at temperatures from 600 to 800 ° C at a speed of 4-6 ° C / min;

- foaming for 10 minutes at temperatures from 800 to 850 ° C at a speed of 4-6 ° C / min;

- decrease in temperature over 45 minutes to 560 ° C at a rate of 6 ° C / min;

- decrease in temperature for 30 minutes from 560 to 480 ° C at a rate of 2 ° C / min;

- slow cooling to 20 ° C at a rate of 1 ° C / min.

Sintered BKS bioceramics blanks are removed from the molds and sawn into blocks and plates, the dimensions of which are shown in Table 1. Billets having cracks or cavities with a diameter of more than 2 mm are crushed in a jaw crusher to obtain granules and powders. The size of the obtained granules and powders are presented in table 2.

The resulting implant materials are washed in an ultrasonic cleaner using distilled water, dried, packaged and labeled.

Example 1. The composition of the mixture to obtain granules and powders of different dispersion from bioceramics of silicocalcium phosphate "BCS" for maxillofacial surgery, dentistry and traumatology.

The bioactive phase and the vitreous matrix are taken in a volume ratio of 4: 1. The ratio of the fractions (0.9-0.7) mm, (0.7-0.4) mm and (0.4-0.2) mm of the bioactive phase is 1: 2: 2, respectively.

Example 2. The composition of the mixture of bioceramics to obtain porous blocks and plates from bioceramics of silicocalcium phosphate "BCS" for maxillofacial surgery, neurosurgery and traumatology.

The bioactive phase and the vitreous matrix are taken in a volume ratio of 1: 1. The ratio of fractions (2.0-1.0) mm and (1.0-0.9) mm of the bioactive phase is 2: 1, respectively.

Example 3. A method of producing granules and powders of different dispersion according to example 1.

Obtained in example 1, the mixture is poured into a mold, compacted using a manual prepress and sintered in an electric laboratory furnace according to the specified mode. Sintered samples intended for granulation are sawn into cubic blocks with a rib size of 25 mm, and they are poured into a jaw crusher, the slot width of which, depending on the required size of granules and powders, varies from 0.1 to 10 mm. Sieving of granules and powders into fractions is carried out for 5-10 minutes on a vibrating screen with a sieving amplitude of 1.5-3.0 mm The actual product yield is:

3.00-4.00 8% 2.00-3.00 10% 1.00-2.00 12% 1.00-0.67 13% 0.67-0.39 13% 0.39-0.20 19% 0.20-0.09 25%

Example 4. A method of manufacturing blocks and plates according to example 2.

Obtained in example 2, the mixture is poured into the mill and mixed with a glass rotation speed of 60 rpm for 5 minutes. The prepared mixture is placed in a mold, compacted on a hydraulic press under a load of 50 kN and sintered in an electric laboratory furnace. A feature of the temperature-time mode of sintering is to increase the speed by 5 ° C / min when heated to 850 ° C and to reduce the sintering time by 2 times, which provides a material with a more developed pore structure.

Next, the resulting workpiece is sawn into blocks, plates and milled with a cutter speed of up to 20,000 rpm. After machining, the implants are washed with distilled water using ultrasound at a frequency of 42000 Hz at a temperature of 50 ° C for 10 minutes. Implant drying occurs at a temperature of 120 ° -150 ° C for 3-4 hours.

Table 1 Characteristics of rectangular blocks and plates made of bioceramics "BCS" Form of bioceramics "BCS" The volume (area *) of the filled cavity, cm ³ Size mm 1. Plates

100.0 * ± 5.0 100 × 100 × 7

25.0 * ± 3.0 50 × 50 × 5

4.0 * ± 1.0 20 × 20 × 5 2. Blocks

19.0 ± 1.0 45 × 20 × 20

12.5 ± 0.5 30 × 20 × 20

10.5 ± 0.5 35 × 17 × 17

7.0 ± 0.5 30 × 15 × 15

4.0 ± 0.2 17 × 15 × 15

The tolerance on the linear dimensions of BKS bioceramics is ± 2 mm.

table 2 Characteristics of granules and powders from bioceramics "BCS" No. Form, size of granules and powders, mm Cavity filling without sealing, cm ³ Mass g one 2 3 four one 3-4 0.5 0.2 ± 0.1

1,0 0.3 ± 0.1 2.0 0.8 ± 0.1 3.0 1.3 ± 0.1 5,0 2.2 ± 0.2 10.0 4.7 ± 0.2 2 2-3 0.5 0.2 ± 0.1

1,0 0.3 ± 0.1 2.0 0.8 ± 0.1 3.0 1.3 ± 0.1 5,0 22 ± 02 10.0 4.7 ± 0.2 3 1-2 0.5 0.2 ± 0.1

1,0 0.3 ± 0.1 2.0 0.8 ± 0.1 3.0 1.3 ± 0.1 5,0 2.2 ± 0.2 10.0 4.7 ± 0.3 four 1-0.67 0.5 0.2 ± 0.1

1,0 0.3 ± 0.1 2.0 0.8 ± 0.1 3.0 1.3 ± 0.1 5,0 2.2 ± 0.2 10.0 4.7 ± 0.3 one 2 3 four 5 0.67-0.39 0.5 0.3 ± 0.1

1,0 0.4 ± 0.1 2.0 1.0 ± 0.1 3.0 1.5 ± 0.1 5,0 2.5 ± 0.2 10.0 5.0 ± 0.3 6 0.39-0.2 0.5 0.3 ± 0.1

1,0 0.5 ± 0.1 2.0 1.2 ± 0.1 3.0 1.8 ± 0.1 5,0 3.0 ± 0.2 10.0 5.5 ± 0.3 7 0.2-0.09 0.5 0.3 ± 0.1

1,0 0.6 ± 0.1 2.0 1.3 ± 0.1 3.0 2.2 ± 0.1 5,0 3.6 ± 0.2 10.0 7.0 ± 0.3

The developed composition of bioceramics of silicocalcium phosphate “BCS” and the method of its manufacture provides biocompatible and heat-conducting implant materials with open porosity of up to 70%, water absorption of at least 65% and a change in the pH in physiological saline from 6 to 9 units, which contributes to the process of bone tissue regeneration when replacing defects and deformations of the bone.

The clinical relevance of using BKS bioceramics in the form of porous blocks, plates, granules and powders of various dispersion in maxillofacial surgery, dentistry, neurosurgery and traumatology has been proven to eliminate:

- major defects and deformations of the congenital and acquired nature of the human skeleton after removal of benign tumors on various bones, as well as gunshot wounds and osteomyelitis;

- medium and small postoperative defects of the bones of the facial and brain skull and alveolar processes of the upper and lower jaws of various etiologies and sinus lift;

- large, medium and small periodontal defects of the bone tissue of the jaws.

Claims (3)

1. Bioceramic silica-calcium phosphate "BCS" containing hydroxyapatite, a sodium silicate matrix and pore formers of organic and inorganic origin, characterized in that it additionally contains wollastonite and β-tricalcium phosphate, which forms a bioactive phase with hydroxyapatite, and the fractional composition of the bioactive phase and matrix thereof volumetric content from 1: 1 to 4: 1. 2. Bioceramics according to claim 1, characterized in that the sodium silicate matrix is made with a specific surface area of up to 2.4 m ² / g and its content does not exceed 35 wt.%, And carbonate having a specific surface area of up to 3.0 is used as a blowing agent m ² / g in an amount up to 10 wt.%. 3. The method of manufacturing bioceramics according to claim 1 is based on heat treatment of a mechanical mixture of bioresorbable and bioresistive components, characterized in that the heat treatment is carried out by heating the mixture to a temperature of 600 ° C for 60 minutes, sintering at temperatures from 600 to 800 ° C for 40 min, foaming at temperatures from 800 to 850 ° C for 10 min, followed by a decrease in temperature to 560 ° C for 45 min, a decrease in temperature from 560 to 480 ° C for 30 min, a further decrease in temperature to 20 ° C occurs inertial mode mu cooling furnace.