An integrated high-strength implant and method of manufacture

Abstract

The application belongs to the field of dental implant, and particularly relates to an integrated high-strength implant and a manufacturing method, the high-strength implant comprising an implant and an abutment, the abutment being arranged at the end of the implant, and the abutment being integrally formed with the implant, the surface of the implant being provided with uniform primary and secondary pores, the diameter of the primary pores being 20-100 um, and the diameter of the secondary pores being 1-10 um. The implant has excellent mechanical properties and biocompatibility.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of dental implant, in particular to a kind of integrated high-strength implant and manufacturing method. BACKGROUND

[0002] Dental implant is a kind of artificial tooth for replacing natural tooth to perform chewing, pronunciation and aesthetic function after dentition defect or loss.Commonly used materials are pure titanium or titanium alloy, which has good bone integration performance, but metal material has ion elution, allergy, neck margin gray line, blue light penetration, easy to adhere bacteria and other defects, so that the research and development of replacement material is imperative.

[0003] Ceramic material gradually becomes a new generation of artificial tooth implant material due to its good biocompatibility and aesthetic appearance.In the past ten years, ceramic implants have been applied in clinical practice, but ceramic implants also have the phenomena of breakage, infection and insufficient bone integration during use.

[0004] The reasons for the above phenomena mainly include the following three aspects: 1) the design of the shape and structure of the ceramic implant has defects, which causes stress concentration to be distributed in a small area, and the area is subjected to excessive stress for a long time, thereby causing breakage;2) the manufacturing process of the ceramic implant (including forming, sintering and machining) has defects, which makes the densification and strength of the ceramic implant difficult to meet the requirements;3) the surface treatment of the ceramic implant is difficult, because the ceramic material usually has high hardness, the surface treatment is difficult, and the surface structure, morphology and roughness formed by the surface treatment process are not ideal, so that the bone integration site is less and the bone integration amount is insufficient. SUMMARY

[0005] In order to improve the deficiencies of the prior art, the present application provides an integrated high-strength implant and a manufacturing method, which has excellent mechanical properties and biocompatibility.

[0006] In a first aspect, the present application provides an integrated high-strength implant, which comprises an implant and an abutment, the abutment is arranged at the end of the implant, and the abutment is integrally formed with the implant, and the surface of the implant has uniform primary and secondary pores, the diameter of the primary pores is 20-100um, and the diameter of the secondary pores is 1-10um.

[0007] According to the embodiment of the present application, the abutment is used to extend to the outside of the gum, constitute a part inside the mouth and through the gum, and connect with the restoration, the implant and the abutment are made by integrated forming technology, which avoids the connection problem in the traditional two-segment design, and improves the stability and durability of the overall structure.

[0008] According to the embodiment of the present application, the abutment is provided with a square slot for connecting the crown, which makes the crown more resistant to rotation, improves the accuracy and convenience of wearing the tooth.

[0009] According to the embodiment of the present application, the outer wall of the abutment is provided with a connecting groove for cooperating with an external carrier and a protective cap, for example, the external carrier can be clamped into the groove, when in use, the user can reduce the number of times of touching the implant when transferring or using the implant by clamping the carrier, which can avoid contaminating and scratching the surface of the implant, and the implant is easy to take and place.

[0010] According to the embodiment of the present application, the implant comprises a soft tissue connecting area and a threaded area, the soft tissue connecting area is located at the upper part of the implant, and corresponds to the soft tissue after the implant is implanted, the soft tissue connecting area has a circular arc structure, which can provide an attachment platform for the soft tissue to form a hemidesmosome connection, prevent bacteria from entering the alveolar bone and causing inflammation, and cause implant failure.

[0011] According to the embodiment of the present application, the lower part of the threaded area is provided with a cutting edge, the cutting edge is eccentric by 0.1-0.5mm, preferably the cutting edge is eccentric by 0.1-0.3mm.

[0012] According to the embodiment of the present application, the threaded area comprises a base, and threads protrude radially outward from the surface of the base, the diameter of the threaded area gradually decreases from top to bottom, and the diameter of the bottom of the threaded area is 0.1-0.5mm smaller than the diameter of the top.

[0013] According to the embodiment of the present application, the threads of the threaded area are multi-threaded threads, for example, double-threaded or triple-threaded, the lead of the multi-threaded thread (i.e. the distance in the axial direction that the thread advances per revolution) is a multiple of the pitch of the single-threaded thread, which greatly reduces the time of implantation surgery, for example, the lead of the triple-threaded thread is three times the pitch of the single-threaded thread, thereby speeding up the implantation.

[0014] According to the embodiment of the present application, the threaded surface is a smooth structure.

[0015] In a second aspect, the present application provides a forming method of the above-mentioned integrated high-strength implant, comprising the following steps:

[0016] S1. The ceramic powder is loaded into a mold, and after sealing, cold isostatic pressing is performed to obtain a green body;

[0017] S2. The green body is debound and then sintered to obtain a blank;

[0018] S3. The blank is machined to obtain an implant semi-finished product;

[0019] S4. The implant semi-finished product is sandblasted and acid-etched to obtain an implant.

[0020] According to an embodiment of the present application, the ceramic powder is at least one of alumina powder, zirconia powder, alumina toughened zirconia powder or zirconia toughened alumina powder, for example zirconia powder.

[0021] According to an embodiment of the present application, the particle size of the zirconia powder is 1-100 nm, preferably the particle size of the zirconia powder is 5-50 nm, and more preferably the particle size of the zirconia powder is 10-30 nm.

[0022] According to an embodiment of the present application, the mold is made of elastic material, for example rubber or plastic.

[0023] According to an embodiment of the present application, the cold isostatic pressing comprises the following steps: placing the mold containing the ceramic powder into the high pressure cavity of the cold isostatic pressing machine, starting the machine, gradually applying pressure to 250±50 MPa, maintaining the pressure for 5-10 minutes, and compacting the powder under uniform pressure.

[0024] According to an embodiment of the present application, between steps S1 and S2, the following step is included: releasing the pressure of the high pressure cavity at a rate of 15±5 MPa / min, demolding, and obtaining the green body.

[0025] According to an embodiment of the present application, the debinding comprises the following steps: heating the green body at a temperature of 400-700℃ for 2-4 hours.

[0026] According to an embodiment of the present application, the sintering comprises the following steps: debinding the green body, and then heating at 1200-1650℃ for 2-6 hours.

[0027] According to an embodiment of the present application, the debinding comprises the following steps: heating the green body to 700-1200℃ at a rate of 50-100℃ / h, maintaining the temperature for 1-2 hours, and then heating to the sintering temperature at a rate of 100-200℃ / h.

[0028] According to an embodiment of the present application, between steps S2 and S3, the following step is included: cooling the sintered green body to below 450℃±100℃ at a rate of 100℃±20℃ / h, and then naturally cooling to room temperature to obtain the implant blank.

[0029] According to an embodiment of the present application, the machining comprises rough machining and finish machining, wherein the rough machining is performed using a general alloy end mill with a tool selection of 5-10 mm, and the finish machining is performed using a special alloy end mill with a tool selection of 1-10 mm.

[0030] According to an embodiment of the present application, the sandblasting is performed on the machined implant semi-finished product.

[0031] According to the embodiments of the present application, the sandblasting treatment comprises spraying sand balls to the surface of the implant semi-finished product. Preferably, the sand balls are selected from boron carbide, zirconium oxide or aluminum oxide, preferably zirconium oxide, more preferably aluminum oxide. Preferably, the diameter of the sand balls is 50-500 μm, preferably 80-400 μm, more preferably 100-200 μm. Further, the pressure of the sandblasting is 1-10 bar, for example 2-5 bar; the working distance of the sandblasting is 10-50 mm, for example 15 mm, preferably 8-10 mm; the moving speed of the sandblasting is 1-20 mm / s, for example 5 mm / s.

[0032] According to the embodiments of the present application, the etching treatment comprises etching the surface of the sandblasted implant semi-finished product with an etching solution.

[0033] According to the embodiments of the present application, the etching solution comprises a first acid and hydrofluoric acid. Preferably, the first acid can be selected from at least one, two or more of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, etc. Further, the hydrofluoric acid is selected from 30-50 vol% hydrofluoric acid; the first acid is selected from 50-80 vol% nitric acid or 30-50 vol% sulfuric acid, 40-60 vol% phosphoric acid. More preferably, the etching solution is obtained by mixing 30-50 vol% hydrofluoric acid with 50-80 vol% nitric acid, preferably 35-45 vol% hydrofluoric acid with 60-70 vol% nitric acid. Exemplarily, the etching solution comprises hydrofluoric acid (40 vol%) and nitric acid (50 vol%) with a volume ratio of 4:6.

[0034] According to the embodiments of the present application, in the etching solution, the volume ratio of the hydrofluoric acid and the first acid is (2-8):(8-2), preferably (4-6):(6-4), more preferably 4:6.

[0035] According to the embodiments of the present application, the etching time is 1 min-120 min, preferably 20-40 min, more preferably 30 min.

[0036] According to the embodiments of the present application, the etching temperature is 30-100℃, for example 70℃, 80℃.

[0037] Advantages

[0038] 1) The integrated high-strength implant in the present application comprises an implant and an abutment, the abutment is arranged at the end of the implant, and the abutment is integrally formed with the implant. The integrated implant is easy to install, which improves the operation efficiency. At the same time, the connection problem in the traditional two-segment design is avoided, and the stability and durability of the overall structure are improved.

[0039] 2) The integrated high-strength implant in the application, the lower part of the implant is provided with a threaded area, the diameter of the threaded area gradually decreases from top to bottom, and the thread of the threaded area is a multi-thread thread, which not only has a large lead, but also has a large surface area, can accelerate the implantation speed, provide more attachment sites, and improve the stability of the implant.

[0040] 4) The integrated high-strength implant in the application, the thread of the threaded area is a smooth thread, which can avoid stress concentration, achieve the effect of dispersing force, reduce the occurrence of implant mechanical complications, and improve the success rate of surgery.

[0041] 5) The material in the application is a zirconia ceramic material, zirconia powder with a particle size of 5-50 nanometers is selected, and the obtained zirconia implant embryo has a monoclinic phase content of less than 2% before aging and a monoclinic phase content of less than 3% after aging; the four-point bending strength before aging is greater than 2000MPa, the four-point bending strength after aging is greater than 1800MPa, the fracture toughness is greater than 10MPa·m 1 / 2 , and the Young's modulus is greater than 210GPa and the hardness is greater than 12GPa, so that the strength of the implant is high and the service life is long; and the zirconia ceramic has good light transmittance and color stability, which can meet the demand of patients for aesthetics.

[0042] 6) The inventor accidentally found that under certain conditions, sandblasting and acid etching are carried out first, and uniform primary and secondary pores are formed on the surface of the implant, the diameter of the primary pores is 20-100um, and the diameter of the secondary pores is 1-10um, the primary and secondary pores are formed to make osteoblasts grow in the pores, which greatly improves the stability of the product. BRIEF DESCRIPTION OF DRAWINGS

[0043] Figure 1 It is a structure diagram of the integrated high-strength implant cooperating with the carrier body Figure 1 , wherein the A-direction schematic diagram refers to the top view and the bottom view along the A-direction);

[0044] Figure 2 It is a physical diagram of the integrated high-strength implant;

[0045] Figure 3 It is a schematic diagram of measuring the surface area of the single-thread threaded part product;

[0046] Figure 4 It is a schematic diagram of measuring the surface area of the double-thread threaded part product;

[0047] Figure 5 It is a static compression schematic diagram of YY / T 0521-2018 product;

[0048] Figure 6Finite element analysis results schematic diagram for non-smooth design of thread;

[0049] Figure 7 Finite element analysis results schematic diagram for smooth design of thread;

[0050] Figure 8 Process flow chart for ceramic dental implant;

[0051] Figure 9 Ceramic implant after sandblasting and acid etching under light microscope view of ×100;

[0052] Figure 10 Ceramic implant after sandblasting and acid etching under light microscope view of ×500;

[0053] Figure 11 Ceramic implant after sandblasting and acid etching under light microscope view of ×2000;

[0054] Figure 12 Ceramic implant after sandblasting and acid etching under light microscope view of ×5000;

[0055] Figure 13 Animal experiment experimental animal weight change curve with period;

[0056] Figure 14 Animal experiment in the experimental group and the control group ceramic implant bone cell growth after 4 weeks, 8 weeks, 13 weeks, 26 weeks Micro-CT examination results pictures;

[0057] Figure 15 Animal experiment in the total bone volume change curve with period;

[0058] Figure 16 Animal experiment in the experimental group and the control group ceramic implant bone cell growth after 4 weeks, 8 weeks, 13 weeks, 26 weeks hard tissue section methylene blue acid fuchsin staining pictures;

[0059] Figure 17 Animal experiment in the BIC(%) binding rate change curve with period;

[0060] Figure 18 Animal experiment in the hard tissue section analysis chart.

[0061] Figure 1 In the middle, 1-implant, 2-abutment, 3-connection groove, 4-soft tissue connection area, 5-thread area, 6-cutting edge. DETAILED DESCRIPTION

[0062] The structure of the present application will be further described in detail below in connection with specific embodiments. It should be understood that the following embodiments are only illustratively described and explained, and should not be interpreted as limiting the scope of protection of the present application. Any technology realized based on the above description of the present application is covered within the scope intended to be protected by the present application.

[0063] In the description of the present application, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the present application.

[0064] In the description of the present application, it should be noted that unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connection" should be broadly understood, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0065] Example 1: Structure of integrated high-strength implant

[0066] Referring to Figure 1 The integrated high-strength implant includes an implant 1 and an abutment 2, the abutment 2 is arranged at the end of the implant 1, and the abutment 2 is integrally formed with the implant 1, the abutment 2 is used to extend to the outside of the gum to form a transgingival part and connect with a restoration, the implant 1 and the abutment 2 are made by integrated forming technology, avoiding the connection problem in the traditional two-section design, and improving the stability and durability of the overall structure.

[0067] The abutment 2 is provided with a square slot, and the square slot is used to connect a crown, and the square slot makes the crown more resistant to rotation, improving the accuracy and convenience of wearing the implant.

[0068] The outer wall of the abutment 2 is provided with a connecting groove 3, referring to Figure 2 The connecting groove 3 is used to cooperate with an external carrying body, for example, the external carrying body can be clamped into the groove 3, when using, the user can reduce the number of times of touching the implant 1 when transferring or using the implant 1, avoiding scratching the surface of the implant 1, and at the same time, the implant is easy to take and place.

[0069] The implant 1 comprises a soft tissue connecting area 4 and a threaded area 5, the soft tissue connecting area 4 is located at the upper part of the implant 1, and corresponds to the soft tissue after the implant 1 is implanted, the soft tissue connecting area 4 is in a circular arc structure, the radius of the circular arc structure is R1-R5, the soft tissue connecting area 4 can provide an attachment platform for the soft tissue, and the arc structure can be fitted and covered on the surface of the soft tissue, and a semi-bridge grain connection is formed between the two, forming a seamless structure, preventing bacteria from entering the alveolar bone from the gap between the soft tissue connecting area 4 and the soft tissue, causing inflammation, and thus leading to implant failure.

[0070] The lower part of the threaded area 5 is provided with a cutting edge 6, the height of the cutting edge 6 is 5-10mm, and the cutting edge 6 is eccentric by 0.1-0.5mm, the purpose of setting the cutting edge 6 is to make the implant 1 operator implant the product more labor-saving, as we all know, M=F*L, when the torque M is constant, the smaller the L is, the larger the F is, and the cutting force generated is larger, so it is more labor-saving; The bottom end of the implant 1 is circular, which can prevent the maxillary sinus from being perforated, making the product safer.

[0071] The threaded area 5 comprises a base body, and threads protrude radially outward from the surface of the base body, the diameter of the threaded area 5 gradually decreases from top to bottom, and the diameter of the bottom of the threaded area 5 is smaller than that of the top by 0.1-0.5mm, the larger the diameter of the threaded area 5 is, the greater the shear force that the implant 1 can withstand is, and the larger the contact area with the alveolar bone is, and the better the stability of the product is, and this design increases the mechanical stability of the product.

[0072] The diameter of the threaded area 5 gradually decreases from top to bottom (hereinafter referred to as a gradually changing thread) has the following advantages:

[0073] I. Initial stability

[0074] 1. The diameter of the thread of the dental implant gradually decreases from top to bottom during implantation, which can make the implant have a closer contact with the surrounding bone tissue. For example, in the early stage of implantation, the thicker thread can first contact the bone cortex, and as the implantation depth increases, the thread gradually becomes thinner and better fits the cancellous bone. This close fit is like a specially designed key inserted into the corresponding lock hole, increasing the friction between the implant and the bone tissue, thereby effectively improving the initial stability of the implant.

[0075] 2. Compared with the traditional equidistant and thick thread, the gradually changing thread can adapt to different bone conditions (such as areas with different bone densities) and better grasp the bone tissue in areas with lower bone density, reducing the micromotion of the implant after implantation and creating good conditions for subsequent bone integration.

[0076] 3. The progressive thread can better disperse the stress that the implant receives under functional load to the surrounding bone tissue. When the patient chews food and so on to generate occlusal force, the implant receives axial and lateral force, and the progressive thread structure can make the stress more evenly distributed to the bone tissue along the progressive direction of the thread.

[0077] II. Bone integration aspect

[0078] 1. The progressive thread structure is similar to building a "growth track" for bone cells, which is conducive to the deposition and growth of new bone on the surface of the implant. Compared with traditional threads, the progressive thread can promote the contact and integration of bone tissue with the implant in the early stage after implantation, shortening the bone integration time.

[0079] 2. Increase the bone integration area: due to the shape characteristics of the progressive thread, it can provide a larger bone integration area under the same implant size. With the progression of the thread, the contact area between the implant surface and the bone tissue is increased in three-dimensional space. For example, during the change of the thread from thick to thin, the contact mode of each circle of thread with the bone tissue is different, and more bone tissue can interact with the implant surface as a whole, which is like building a wider "connection bridge" between the implant and the bone tissue, thereby improving the quality and strength of bone integration and facilitating the long-term stable existence of the implant in the jaw bone.

[0080] III. Aesthetic effect aspect

[0081] 1. Gum shape maintenance: the progressive thread implant has good support effect on the gum tissue. After implant restoration, the appropriate implant structure helps to maintain the natural shape of the gum. Due to its good initial stability and bone integration performance, the bone tissue around the implant can remain stable, thereby providing stable support for the gum. For example, in single tooth implant restoration, the progressive thread implant can avoid gum recession caused by implant loosening or bone resorption, making the contour of the gum edge more natural and beautiful, meeting the requirements of aesthetic restoration.

[0082] 2. Reduce soft tissue complications: the progressive thread implant is conducive to the health of the soft tissue around the implant. The progressive thread can make the implant better adapt to the physiological environment in the oral cavity, reduce the stimulation to the surrounding soft tissue, because it can maintain a stable position during implantation and functional load, and will not cause damage to the gum and other soft tissues due to micromotion.

[0083] 3. Compared with non-progressive thread implants, the progressive thread implant can reduce the incidence of soft tissue complications such as peri-implantitis around the implant, which is conducive to maintaining the aesthetics and health of the soft tissue in the oral cavity after implant restoration.

[0084] The thread in threaded area 5 is a multi-start thread, such as a double-start or triple-start thread. The lead of a multi-start thread (i.e., the distance the thread travels axially per revolution) is a multiple of that of a single-start thread with the same pitch. This greatly reduces the time required for implantation surgery. For example, the lead of a triple-start thread is three times the pitch of a single-start thread, thus speeding up the implantation process.

[0085] Multi-start thread design maintains a fast insertion speed while increasing thread density and surface area. See [link / reference] Figure 3 and Figure 4 As shown, The surface area of ​​the threaded portion of a single-threaded wire and The diagram shows the surface area measurement of the threaded portion of the double-threaded structure. The surface area of ​​the threaded portion of the single-threaded structure is 172.26 square millimeters, and the surface area of ​​the threaded portion of the double-threaded structure is 174.11 square millimeters. It can be seen that the multi-threaded structure has a larger surface area and can provide more attachment sites. This allows the implant 1 to achieve better stability in the early stage. This design helps to reduce vibration and displacement of the implant 1 after implantation, thereby improving the long-term success rate of the implant 1.

[0086] Furthermore, the threaded structure is an important structure for maintaining the bone volume in the neck. When the implant 1 is functioning, the force transmitted to the bone-implant interface by the implant 1 with a smooth neck design is mainly shear force. Shear force is the force that causes the most damage to bone tissue. Compared with shear force, bone tissue has a higher tolerance to pressure and tension. The multi-threaded design in this invention changes the type of force at the bone-implant interface, increases the tolerance of the bone tissue around the implant, and thus effectively reduces bone resorption in the implant neck.

[0087] The threaded structure in the neck allows the implant to better adapt to the physiological function of the surrounding bone and preserve the surrounding bone. The large threads at the bottom of the implant mainly increase mechanical stability in the early stage and increase osseointegration stability in the later stage. The threads in the neck do not play a role in increasing initial stability in the early stage of implantation, but reduce stress concentration in the neck. In the later stage, they reduce stress concentration during occlusion, convert shear force into tensile or compressive stress, reduce bone resorption, and promote osseointegration.

[0088] When the implant material is zirconia, the failure of the zirconia implant 1 is usually due to stress concentration, which leads to point breakage and then extends to the line, causing the entire implant 1 to break. To solve this problem, the present invention uses a circular arc thread with a smooth R0.1-R0.5 design to avoid stress concentration and achieve the effect of dispersing force, which greatly improves the success rate of surgery. The tooth angle of the circular arc thread is 30-60° and the thread height is 0.3-0.6mm.

[0089] According to the product embedding mode and mechanical loading mode of the regulation YY / T 0521-2018, static pressure of 200N is applied to the smooth implant and the non-smooth implant in this embodiment at the same time (the other structures of the two implants are the same, and each implant is tested in three groups in parallel), as shown in Figure 5 Fig. 1 is a schematic diagram of static compression of the product according to the regulation YY / T 0521-2018.

[0090] As shown in Figure 6 and Figure 7 Fig. 2, the smooth and non-smooth threaded implants are analyzed by three finite element methods and statistics, as shown in Tables 1 and 2, the average maximum stress of the non-smooth threaded product is 851.97Mpa, and the average maximum stress of the smooth threaded product is 644.03Mpa, so the smooth threaded implant 1 is less stressed than the non-smooth threaded product, that is, the smooth threaded product can effectively disperse stress and avoid stress concentration.

[0091] Table 1 Finite element analysis results of the implant with non-smooth thread

[0092]

[0093] Table 2 Finite element analysis results of the implant with smooth thread

[0094] Group Maximum stress 1 642.7 Mpa 2 644.4 Mpa 3 645.0 Mpa Average 644.03 Mpa

[0095] Example 2: Forming method of integrated high-strength implant

[0096] The raw material in this embodiment is zirconia powder, and the selection of zirconia powder directly affects the mechanical properties of the implant. The inventors have unexpectedly found that when the particle size of the zirconia powder is 5-50 nanometers, the mechanical properties of the implant are the best.

[0097] As shown in Figure 8 The forming method of the zirconia powder includes the following steps:

[0098] I. Powder loading and cold isostatic pressing:

[0099] The zirconia powder is placed in an elastic mold, sealed and placed in a high-pressure container, and a uniform static pressure of the liquid medium is generated on the mold by a high-pressure pump, and the powder is compacted under isotropic pressure to form a green body with certain density and strength.

[0100] 1) Mold preparation:

[0101] An elastic mold is made according to the shape and size of the implant, usually made of rubber or plastic, etc., to ensure that the mold has good flexibility and sealing performance.

[0102] 2) Compaction:

[0103] An appropriate amount of zirconia powder is loaded into the mold and placed in the high-pressure cavity of the cold isostatic pressing machine. The machine is started, and the pressure is gradually applied to about 250±50 MPa, and the pressure is maintained for 5-10 minutes to compact the powder under uniform pressure.

[0104] 3) Demolding treatment:

[0105] After compaction, the pressure is slowly released until the pressure is 0 MPa before the mold can be removed. The rate of pressure release is 15±5 MPa / min. The mold is removed and demolded to obtain the zirconia green body.

[0106] II. Sintering:

[0107] 1) Degreasing treatment:

[0108] Before sintering, the zirconia green body needs to be degreased to remove organic matter and impurities such as binders, etc. from the green body. Degreasing is usually done at a temperature of 400-700°C for a certain period of time, which depends on the size and shape of the green body, usually 2-4 hours.

[0109] 2) Heating stage:

[0110] After degreasing, the degreased green body is heated. The heating rate should not be too fast to avoid cracks or deformation of the green body due to thermal stress. Multi-stage heating is usually used, such as first heating at a rate of 50-100°C / h to 700-1200°C for 1-2 hours, and then heating at a rate of 100-200°C / h to the sintering temperature.

[0111] 3) Sintering stage:

[0112] The sintering temperature is usually between 1200°C and 1650°C, and the holding time is 2-6 hours. In this stage, the particles in the green body migrate, the pores are removed, and the green body is gradually densified.

[0113] 4) Cooling stage:

[0114] After sintering, the cooling stage is entered, and the cooling rate is 100°C±20°C / h to below 450°C±100°C, and then naturally cooled to room temperature to obtain the implant blank.

[0115] The mechanical and index tests of the implant embryo made by the forming process of the application are shown in the following table. The data show that the implant embryo made by the forming process of the application has significant improvement in various indexes.

[0116] Referring to Table 3, the implant blank is obtained by static pressure and sintering according to the above steps.

[0117] Table 3 Forming conditions of zirconia powder of different embodiments

[0118]

[0119] Table 4 Indexes of the implant embryo prepared in Example 4

[0120]

[0121] Example 7 Machining and surface treatment

[0122] The implant embryo obtained in Examples 3-6 is machined to obtain the structure in Example 1. The machining is divided into two steps, i.e., rough machining and fine machining. The rough machining is performed by using a general alloy end mill with a diameter of 5-10 mm, and the fine machining is performed by using a special alloy end mill with a diameter of 1-10 mm.

[0123] Surface treatment process

[0124] Sandblasting and acid etching of the ceramic implant is a surface treatment technology for improving the bonding ability of the implant and the surrounding bone.

[0125] Sandblasting treatment is to impact a certain diameter of particulate matter at high speed onto the surface of the implant semi-finished product to form a certain roughness. Such rough surface can increase the surface area of the implant, provide more space for new bone formation, and be conducive to the generation of bone bonding. At the same time, appropriate roughness is conducive to the adhesion, proliferation, division, differentiation, secretion of extracellular matrix and osteogenesis of osteoblasts.

[0126] Acid etching treatment is to expose the implant to a certain concentration of acid solution for chemical reaction, and the surface of the implant semi-finished product will form micro-holes. These holes can promote the attachment of pseudopods of osteoblasts and be conducive to the growth of bone cells.

[0127] The present application performs sandblasting and acid etching treatment on the machined implant semi-finished product. After sandblasting and acid etching, the surface of the product can form uniform primary and secondary holes. The primary holes are 20-100 um, and the secondary holes are 1-10 um. The primary and secondary holes formed can make osteoblasts grow in the holes and greatly improve the stability of the product.

[0128] In particular, the sandblasting treatment is performed on the machined implant semi-product, which comprises spraying sand balls onto the surface of the implant semi-product, wherein the sand balls are selected from boron carbide, zirconium oxide or aluminum oxide, preferably zirconium oxide, and more preferably aluminum oxide. Preferably, the diameter of the sand balls is 50-500 μιη, preferably 80-400 μιη, and more preferably 100-200 μιη. Further, the pressure of the sandblasting is 1-10 bar, for example 2-5 bar; the working distance of the sandblasting is 10-50 mm, for example 15 mm, and preferably 8-10 mm; and the moving speed of the sandblasting is 1-20 mm / s, for example 5 mm / s.

[0129] The etching treatment comprises treating the surface of the sandblasted implant semi-product with an etching solution.

[0130] The etching solution comprises a first acid and hydrofluoric acid, wherein the first acid is selected from at least one, two or more of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Further, the hydrofluoric acid is selected from 30-50 vol% hydrofluoric acid; and the first acid is selected from 50-80 vol% nitric acid or 30-50 vol% sulfuric acid or 40-60 vol% phosphoric acid. More preferably, the etching solution is obtained by mixing 30-50 vol% hydrofluoric acid with 50-80 vol% nitric acid, preferably 35-45 vol% hydrofluoric acid with 60-70 vol% nitric acid. Exemplarily, the etching solution comprises hydrofluoric acid (40 vol%) and nitric acid (50 vol%) in a volume ratio of 4:6.

[0131] In the etching solution, the volume ratio of the hydrofluoric acid and the first acid is (2-8):(8-2), preferably (4-6):(6-4), and more preferably 4:6.

[0132] The etching time is 1 min-120 min, preferably 20-40 min, and more preferably 30 min.

[0133] The etching temperature is 30-100 °C, for example 70 °C or 80 °C.

[0134] Table 5 Sandblasting and etching conditions for different green bodies

[0135]

[0136] The implant prepared in Example 11 is compared with a comparative product on the market (from bredent medical, named Zirconia implant, trade name wSKYT3508, batch number 510132), and it is proved that the bone cell growth effect of the product prepared in the application (experimental group) is better than that of the product on the market (control group), see Table 6.1, Table 6.2 experimental group and control group animal experiment Micro-CT detection data, Table 7 experimental group and control group animal experiment hard tissue section detection data, from Table 6.1, Table 6.2, Table 7, Figure 14 , Figure 15 , Figure 16 , Figure 17 , Figure 18 It is known that the ceramic implant prepared by the sandblasting and acid etching process of the application has hard bone uniformly distributed on the surface of the product, and the bone growth area is larger than that of the competitive product, and it is proved that the sandblasting and acid etching process prepared in the application is superior to the surface treatment process existing on the market.

[0137] Materials for animal experiments:

[0138] 1. Experimental animals: several healthy adult beagle dogs, weighing 15-20 kg, half male and half female, without oral cavity diseases and systemic diseases.

[0139] 2. Ceramic implant: ceramic implant customized according to the size of beagle dog alveolar bone (ceramic implant prepared according to the method of Example 11), the surface is treated by sandblasting and acid etching to facilitate bone bonding.

[0140] 3. Surgical instruments: conventional oral implant surgical instruments, including implant machine, dental drill, screwdriver, etc., which are strictly sterilized.

[0141] 4. Imaging equipment: micro-CT, X-ray machine, used for imaging examination before and after implantation and at different time points after operation.

[0142] 5. Histological detection reagent: fixing solution, decalcification solution, embedding agent, hematoxylin-eosin (HE) staining reagent, etc.

[0143] Animal experiment method

[0144] 1. Grouping:

[0145] The beagle dogs are randomly divided into experimental group and control group, and the number of each group is determined according to statistical calculation, generally not less than 5 in each group. The experimental group and the control group are implanted with ceramic implants.

[0146] 2. Preoperative preparation:

[0147] The beagle dogs are fasted for 12 hours and water for 6 hours before operation.

[0148] General anesthesia, pentobarbital sodium intravenous injection anesthesia can be used.

[0149] Oral cavity cleaning and disinfection, using iodophor cotton ball to wipe oral mucosa and gingiva.

[0150] 3. Implantation surgery:

[0151] Under sterile conditions, incise the mucosa of the alveolar crest of the beagle dog, and expose the alveolar bone by flap turning.

[0152] According to the specifications of the implant, use the implant machine to prepare the implant socket, pay attention to control the speed and temperature to avoid bone burn.

[0153] Implant the experimental or control group into the implant socket, install the protective cap, and suture the wound.

[0154] 4. Postoperative care:

[0155] Postoperative antibiotics are given to prevent infection, and continuous injection for 3-5 days.

[0156] Postoperative liquid diet for 1 week, then gradually transition to normal diet.

[0157] Regularly observe the healing of the wound, and record whether there are complications such as redness, bleeding, infection, etc.

[0158] 5. Observation index

[0159] 5.1 Clinical observation:

[0160] Examination time: every day after operation

[0161] Examination content: During the postoperative observation period, observe and record the general observation indexes of experimental animals such as appearance, mental state, behavior activity, local irritation, fecal characteristics, and food consumption every day; at the same time, observe whether there are abnormal bleeding and other symptoms after operation. Local symptoms or abnormal death of animals need to be recorded in detail.

[0162] 5.2 Micro-CT examination:

[0163] Examination time: 4 weeks (6), 8 weeks (6), 13 weeks (6), and 26 weeks (6) after operation; one animal from each group was taken.

[0164] Examination content: Through Micro-CT detection of implant and attached bone tissue, including: trabecular bone thickness, trabecular bone number, trabecular bone interval, bone volume of sample tissue, and tissue volume of sample tissue, TB.Th, TB.N, Tb.Sp, BV, TV, and BVITV% values of test and control groups were measured. The results are expressed as mean ± standard deviation, and the P value is calculated by T test. P<0.05 is considered to have statistical significance.

[0165] 5.3 Histological examination:

[0166] Examination time: 4 weeks (6), 8 weeks (6), 13 weeks (6), 26 weeks (6) after operation; samples were used for Micro-CT

[0167] Staining method: methylene blue-acid fuchsin staining

[0168] Examination content: tissue samples from implant site and surrounding area were fixed with 10% neutral formalin, standardised sectioning and grinding, methylene blue-acid fuchsin staining, Im.Pm (implant perimeter), Tb.In.Pm (implant and cancellous bone partial contact perimeter), CtIn.Pm (implant and cortical bone partial contact perimeter) and BIC (bone implant contact, implant-bone contact rate) were measured, results were expressed as mean ± standard deviation, group comparison was made using T test to calculate P value, P<0.05 was considered to have statistically significant difference.

[0169] 6. Statistical analysis of data

[0170] Statistical software was used to analyze experimental data, measurement data was expressed as mean ± standard deviation (x ± s), t test or variance analysis was used for group comparison, P<0.05 was considered to have statistically significant difference.

[0171] 7. Results

[0172] 7.1 Clinical observation:

[0173] All experimental animals survived normally, there were no abnormalities in postoperative behavior and food intake, and no redness, pus and sinus formation occurred in the wound. There were no abnormal symptoms in the nervous system during the operation and postoperative period, and there were no gait instability and overactive behavior during the observation period; the body weight of experimental animals increased normally at 4 weeks, 8 weeks, 13 weeks and 26 weeks after operation (see Figure 13 ), that is, the animals did not cause eating disorders due to surgical operation.

[0174] 7.2 Micro-CT examination:

[0175] Table 6.1 Micro-CT examination results table (X ± S)

[0176]

[0177] Note: n = 3; *P<0.05.

[0178] Table 6.2 Micro-CT examination results table (X ± S)

[0179]

[0180]

[0181] Note: n = 3; *P < 0.05.

[0182] In this study, the BV / TV, Tb.Th, Tb.N, Tb.Sp and total bone volume in the region of interest were calculated accurately by micro-computed tomography (Micro-CT) and related analysis software to analyze the bone regeneration and reconstruction in different bone healing periods.

[0183] BV / TV: trabecular bone volume / total bone volume, which can directly reflect the change of bone mass;

[0184] Tb.Th: average thickness of trabecular bone, which decreases when osteoporosis occurs;

[0185] Tb.N: trabecular bone number, the number of intersections between bone tissue and non-bone tissue within a given length, which decreases when osteoporosis occurs;

[0186] Tb.Sp: average trabecular spacing, the average width of the marrow cavity between trabecular bones, which increases when osteoporosis occurs;

[0187] Total bone volume: the volume of bone tissue in the region of interest

[0188] From Tables 6.1, 6.2, Figure 14 and Figure 15 It can be seen that at 4 weeks, 8 weeks, 13 weeks and 26 weeks after surgery, the bone regeneration and reconstruction of the implants in the test group and the control group did not show significant differences in BV / TV, Tb.Th, Tb.N, TbSp and total bone volume; with the extension of the period, the bone mass around the implant showed a significant increasing trend.

[0189] 7.3 Histological examination:

[0190] Based on the qualified staining, the methylene blue-acid fuchsin stained slices were subjected to quantitative analysis.

[0191] 1. Open OsteoMeasure analysis software under microscope. OsteoMeasure bone measurement software is developed by OsteoMetrics, Inc. It is the most mature and professional bone measurement software in the world, and its measurement results are extremely authoritative and widely recognized internationally. It is an intelligent system for quickly measuring and calculating bone sample parameters. It is a special system for international Chinese bone research society to study bone tissue morphology. The system uses high-pixel CCD, advanced microscope electric platform, and advanced software to enable researchers to automatically or manually measure and analyze bone samples, and can complete all indicators in clinical indicators and basic application research in hospitals. Today, it is widely used in basic medical research and clinical diagnosis as a professional software method for measuring bone tissue and bone morphology. Its authority is widely recognized internationally and is recommended by the International Chinese Bone Research Society.

[0192] 2. Set bone combination morphometric analysis parameters: Implant implant, Ct Interface cortical bone contact surface, Tb Interface cancellous bone contact surface, Ct Bone cortical bone, three parameter names.

[0193] 3. Select the analysis area with the implant under 4x magnification, mark the cancellous bone with Bone, mark the cortical bone with Ct Bone, mark the cancellous bone contact surface with Tb. In. Pm, mark the cortical bone contact surface with Ct. In. Pm, and mark the implant perimeter with Im. Pm.

[0194] 4. Export relevant parameter values and analysis area graphs from the bone tissue morphology analysis system. Organize the data and add units. Form the final data table.

[0195] 5. Cancellous bone blue area, cancellous bone upper blank part, pink outer line middle red area, pink solid area represents cortical bone, light yellow line represents implant and cancellous bone contact surface, dark blue line represents implant and cortical bone contact surface.

[0196] 6. Result calculation: cancellous bone contact surface perimeter + cortical bone contact surface perimeter / implant perimeter = BIC (%) bonding degree

[0197] Results are shown in Table 7:

[0198] Bone implant contact (BIC): bone implant contact area / total available implant area.

[0199] Table 7 Hard tissue section examination results (X vs. S)

[0200]

[0201] Note: BIC = (Tb.In.Pm + Ct.In.Pm) / Im.Pm; n = 3; *P < 0.05.

[0202] From the above table, Figure 16 and Figure 18 It can be seen that the BIC (%) binding rate of each cycle test group and the control group did not show significant difference; a small amount of new bone was visible on the implant surface at the early stage of implantation (4 weeks after operation), and a large amount of new bone was visible on the implant surface at 26 weeks; and from 4 weeks after operation to 26 weeks, the BIC (%) binding rate was positively correlated with the implantation period, that is, the fusion of the implant and the new bone became better and better with the extension of the period; the average value of BIC (%) of the test group reached 37.33% at 4 weeks after operation, 45.00% at 8 weeks after operation, 60.00% at 13 weeks after operation, and 65.67% at 26 weeks after operation.

[0203] 8Conclusion

[0204] The ceramic dental implant (model: Batch number: C2312004) produced by the experimental group Beijing Ruicai Medical Technology Co., Ltd. has high safety and good effectiveness. In terms of safety, there is no obvious difference between the clinical observation of the ceramic dental implant system and the control group; in terms of effectiveness, the ceramic dental implant system does not show significant difference in Micro-CT and bone binding rate compared with the control product, and shows good bone binding effect.

[0205] Since the implant product prepared in the application is a three-class medical device implant, there are strict requirements for the product precision cleaning packaging environment and the initial contaminant bacteria and particles of the product after precision cleaning packaging. The product precision cleaning packaging environment should not be less than 100,000 levels, and the product after precision cleaning packaging should meet the initial contaminant bacteria ≤100 cfu / g, the cleaning parameter is temperature 40-80℃, and the cleaning time is 20-60 minutes.

[0206] Medical devices are sterilized in three ways: irradiation sterilization, ethylene oxide sterilization, and high-pressure steam sterilization. The color of ceramic materials changes after irradiation sterilization, and the mechanical properties decrease, so irradiation sterilization is not used, high-pressure steam sterilization is complex to operate, and at the same time affects the material aging, so high-pressure steam sterilization is also not used, ethylene oxide sterilization does not affect the performance of the product, and batch operation is more convenient, so ethylene oxide sterilization is used. The product needs to be tested after sterilization back to the factory, including product sterility, bacterial endotoxin ≤0.25 EU / mL, and ethylene oxide residue ≤10 μg / g.

[0207] The above has exemplarily illustrated the specific embodiments of the present application through the examples. However, the protection scope of the present application is not limited to the above exemplified embodiments. Any modification, equivalent replacement, improvement, etc. made by the skilled in the art within the spirit and principle of the present application shall be included in the protection scope of the present application claims.

Claims

1. A method of forming an integrated high-strength implant, comprising: The method comprises the following steps: ​ S1. loading ceramic powder into a mold, cold isostatic pressing after sealing to obtain a green body; S2. debinding and sintering the green body to obtain a blank; S3. machining the blank to obtain an implant half-finished product; S4. sandblasting and acid etching the implant half-finished product to obtain an implant; The debinding comprises the following steps: keeping the green body at a temperature of 400-700℃ for 2-4 hours; the sintering comprises the following steps: debinding the green body first, and then keeping it at a temperature of 1200-1650℃ for 2-6 hours; The high-strength implant comprises an implant and an abutment, the abutment is arranged at the end of the implant, and the abutment is integrally formed with the implant, the surface of the implant has uniform primary and secondary pores, the diameter of the primary pores is 20-100um, and the diameter of the secondary pores is 1-10um; The implant comprises a soft tissue connecting area and a threaded area, the soft tissue connecting area is located at the upper part of the implant, corresponds to the soft tissue after the implant is implanted, and has a circular arc structure; the lower part of the threaded area is provided with a cutting edge, and the cutting edge is eccentric by 0.1-0.5mm; The threaded area comprises a base body, threads protrude radially and outwardly from the surface of the base body, the diameter of the threaded area gradually decreases from top to bottom, and the diameter of the bottom of the threaded area is smaller than that of the top by 0.1-0.5mm; the threads of the threaded area are multi-threaded threads, and the surface of the threads is a smooth structure.

2. The molding method according to claim 1, characterized by, The implant powder is at least one of alumina powder, zirconia powder, zirconia toughened alumina powder or alumina toughened zirconia powder.

3. The molding method according to claim 2, characterized by, The implant powder is zirconia powder, and the particle size of the zirconia powder is 1-100nm.

4. The molding method according to claim 2, characterized by, The cold isostatic pressing comprises the following steps: placing the mold loaded with ceramic powder into the high-pressure cavity of the cold isostatic pressing machine, starting the machine, gradually applying pressure to 250±50MPa, keeping the pressure for 5-10 minutes, and compacting the powder under uniform pressure.

5. The molding method according to claim 1, wherein Between steps S1 and S2, the following step is included: unloading the high-pressure cavity at a rate of 15±5MPa / min, demolding, and obtaining a green body.

6. The molding method according to claim 1, characterized by, After debinding in step S2, the temperature is raised, and the temperature raising comprises the following steps: raising the temperature of the green body to 700-1200℃ at a speed of 50-100℃ / h, keeping it for 1-2 hours, and then raising the temperature to the sintering temperature at a speed of 100-200℃ / h.

7. A forming method according to any one of claims 2 to 6, characterised in that, Between steps S2 and S3, the following step is included: cooling the sintered green body to below 450℃±100℃ at a speed of 100℃±20℃ / h, and then naturally cooling it to room temperature to obtain an implant blank.

8. The molding method according to claim 7, characterized by The sandblasting treatment comprises spraying sand balls to the surface of the implant half-finished product, the sand balls are selected from boron carbide, zirconia or alumina, the diameter of the sand balls is 50-500um, the pressure of the sandblasting is 1-10bar, the working distance of the sandblasting is 10-50mm, and the moving speed of the sandblasting is 1-20mm / s.

9. The molding method according to claim 1, characterized by, The acid etching comprises: treating the surface of the sandblasted implant semi-finished product with an etching solution to form a hole structure on the outer surface; the etching solution comprises a first acid and hydrofluoric acid, and the first acid is selected from at least one of hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid.

10. The molding method according to claim 9, characterized by In the etching solution, the volume ratio of the hydrofluoric acid to the first acid is (2-8):(8-2); the etching time is 1 min-120 min, and the etching temperature is 30-100℃.

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