Osteophilic dental implant and method of manufacturing the same

Abstract

This invention relates to the field of dental implants, specifically to an osteogenic dental implant and its preparation method, comprising the following steps: Step 1, mixing osteogenic bioceramic, strontium phosphate, and β-glycerol magnesium phosphate in tantalum metal powder to obtain a mixed raw material; Step 2, 3D printing the mixed raw material to obtain an implant matrix; Step 3, generating a polydopamine coating on the implant matrix to obtain a coated implant; Step 4, bonding a hydrogel to the coated implant to obtain an osteogenic dental implant. The polydopamine coating of this invention forms covalent bonds with the tantalum metal powder through catechol groups and chelates strontium / magnesium ions through quinone groups. Furthermore, the phenolic hydroxyl groups of the polydopamine coating form a hydrogen bond network with the polar groups of the hydrogel, and also exhibit cation-π interactions and hydrophobic synergy with the hydrogel. Therefore, the hydrogel can be indirectly and firmly bonded to the implant matrix through the polydopamine coating.

Description

Technical Field

[0001] This invention relates to the field of dental implants, and more specifically to an osteogenic dental implant and its preparation method. Background Technology

[0002] Implant restoration has become a routine treatment for missing teeth due to its numerous advantages and reliable clinical results. Currently, the vast majority of implants used clinically are prefabricated, dense cylindrical or conical titanium implants. However, related studies have shown that titanium and titanium-based alloy implants have the following three drawbacks: First, the dense structure of the implant does not match the elastic modulus of the jawbone, easily causing a stress shielding effect, leading to implant loosening and dislodgement; second, titanium and titanium-based alloys are bioinert metals, severely lacking osseointegration capacity, making early osseointegration between the implant and the bone interface difficult; third, long-term implantation of alloy implants carries the risk of releasing toxic ions such as Al and V, thus harming human health. Tantalum, due to its good biocompatibility, suitable biomechanical properties, and excellent bioactivity, has become the most promising alternative to titanium implants.

[0003] Tantalum implants are mostly fabricated using 3D printing. However, directly bonding hydrogels doped with functional components (such as antibacterial, angiogenic, and ossification-promoting agents) to tantalum implants has proven difficult. This is primarily due to the tantalum pentoxide passivation layer on the implant surface, which makes it difficult for the hydrogel's polar groups to form covalent bonds with the inert oxide. Additionally, the surface of 3D-printed tantalum implants contains numerous laser-melted pores, making it difficult for the hydrogel to penetrate these pores, resulting in a small actual contact area between the hydrogel and the implant matrix. Therefore, direct bonding of the hydrogel to the tantalum implant is challenging, hindering the realization of its intended function. Summary of the Invention

[0004] To address the challenge of directly bonding hydrogels to tantalum implants, this invention provides a method for preparing bone-friendly dental implants. This method primarily involves generating a polydopamine coating on the implant substrate, which then connects the implant substrate and the hydrogel, thereby indirectly and firmly bonding the hydrogel and the implant substrate together.

[0005] In a first aspect, the present invention provides a method for preparing a bone-compatible dental implant, employing the following technical solution:

[0006] A method for preparing a bone-compatible dental implant includes the following steps:

[0007] Step 1: Mix osteogenic bioceramic, strontium phosphate, and β-glycerophosphate magnesium phosphate in tantalum metal powder to obtain a mixed raw material;

[0008] Step 2: The mixed raw materials are 3D printed to obtain the implant matrix;

[0009] Step 3: Generate a polydopamine coating on the implant substrate to obtain a coated implant;

[0010] Step 4: Adhere the hydrogel to the coated implant to obtain a bone-compatible dental implant.

[0011] By employing the above technical solution, the polydopamine coating forms covalent bonds with tantalum metal powder through catechol groups and chelates with strontium / magnesium ions through quinone groups. Furthermore, the phenolic hydroxyl groups of the polydopamine coating form a hydrogen bond network with the polar groups of the hydrogel, and also exhibit cationic-π interactions and hydrophobic synergy with the hydrogel. Therefore, the hydrogel is indirectly bonded to the implant matrix through the polydopamine coating, allowing more functional components, such as antibacterial and osteogenic factors, to exert their effects by incorporating them into the hydrogel.

[0012] Preferably, the method for preparing the coated implant includes the following steps:

[0013] S1. The implant matrix is ​​added to a dopamine hydrochloride solution, and then copper chloride solution is added dropwise to catalyze the reaction, followed by the addition of Ti3C2.

[0014] S2. After the reaction is complete, add EDTA-disodium and mix. Remove, rinse, and dry to obtain the coated implant.

[0015] By employing the above-mentioned technical solution, copper chloride catalyzes the reaction of dopamine hydrochloride solution, gradually forming a polydopamine coating on the implant substrate. During the catalytic reaction, Ti3C2 promotes accelerated electron transfer and simultaneously inhibits steric hindrance, preventing excessive cross-linking of polydopamine and improving the uniformity of the polydopamine coating thickness. Disodium EDTA chelates excess copper ions after the reaction, preventing excessive copper ion residue on the polydopamine coating.

[0016] Preferably, in step S1, a Ti3C2 suspension is added; the components of the Ti3C2 suspension include Ti3C2, GSH, ethanol and water.

[0017] By employing the above technical solution, directly adding Ti3C2 leads to easy oxidative degradation, while GSH in the Ti3C2 suspension effectively protects its reducing properties. Direct addition of Ti3C2 also easily results in lamellar accumulation and a decrease in effective specific area, while ethanol in the Ti3C2 suspension reduces surface tension and promotes single-layer dispersion. Therefore, replacing Ti3C2 with a Ti3C2 suspension is more conducive to the formation of the polydopamine coating.

[0018] Preferably, in step S1, after the copper chloride solution is added dropwise, the Ti3C2 suspension is added 8-12 minutes after the reaction begins.

[0019] By employing the above technical solution, during the reaction period of 8-12 minutes, the free radicals are at a high concentration, and the three-dimensional network is in its nascent stage, not yet solidified. At this time, the solution viscosity is also favorable for Ti3C2 dispersion. If the Ti3C2 suspension is added too early, it can easily hinder molecular cyclization, resulting in insufficient cross-linking of the coating and uneven thickness. If the Ti3C2 suspension is added too late, the polydopamine coating has already begun to gradually solidify, making it increasingly difficult for Ti3C2 to embed, and the solution also exhibits high viscosity, hindering Ti3C2 dispersion.

[0020] Preferably, in step S1, the reaction time of the catalytic reaction is 40-50 min.

[0021] Preferably, in step S2, EDTA-disodium is added and mixed at pH 8.4-8.6 for 4-6 min, and then mixed at pH 6.9-7.1 for 4-6 min.

[0022] By employing the above technical solution, EDTA-disodium can efficiently chelate copper ions at pH 8.4-8.6, and promote the exposure of amino / carboxyl active sites at pH 6.9-7.1. Stepwise treatment can achieve more beneficial effects.

[0023] Preferably, the method for preparing the hydrogel includes the following steps:

[0024] Sodium alginate, nanocellulose whiskers and water were mixed together, then calcium chloride solution was added dropwise, followed by LAP, and a hydrogel was obtained after UV irradiation.

[0025] By employing the above technical solution, sodium alginate and calcium chloride react and bridge to form a primary ionic gel network. Nanocellulose whiskers are anchored by hydrogen bonds, connecting calcium alginate network fragments; the nanocellulose whiskers also inhibit the swelling and cracking of calcium alginate through the nano-confinement effect. LAP photo-initiated free radical polymerization forms a covalently cross-linked network.

[0026] Preferably, after adding LAP and mixing, sodium ascorbate is added, followed by immediate UV irradiation to obtain a hydrogel.

[0027] By employing the above technical solution, sodium ascorbate can regulate the reduction of free radicals, eliminate oxygen inhibition, and quench toxic byproducts. If UV irradiation is not performed after adding sodium ascorbate, free radicals will be consumed, leading to uneven UV-induced polymerization.

[0028] Preferably, sodium alginate, nanocellulose whiskers, functional ingredients, and water are mixed together, wherein the functional ingredients include at least one of chlorhexidine microcapsules, IGF-1 microcapsules, and BMP-2 mimic peptide microcapsules.

[0029] By employing the above-mentioned technical solutions, chlorhexidine, IGF-1, and BMP-2 mimic peptides, if directly added to hydrogels, are easily oxidized, degraded, and inactivated. Forming them into microcapsules provides excellent protection. Chlorhexidine microcapsules have anti-infection properties, IGF-1 microcapsules promote angiogenesis, and BMP-2 mimic peptide microcapsules promote osteogenic differentiation; all are important functional components for osteogenic implant applications. In addition to the above-mentioned functional components, other types of functional components can also be added.

[0030] Secondly, the present invention provides a bone-compatible dental implant, which adopts the following technical solution:

[0031] A bone-friendly dental implant is prepared by the above-described method for preparing bone-friendly dental implants.

[0032] In summary, the present invention has the following beneficial effects:

[0033] 1. Because the polydopamine coating of the present invention forms covalent bonds with tantalum metal powder through catechol groups and chelates with strontium / magnesium ions through quinone groups; on the other hand, the phenolic hydroxyl groups of the polydopamine coating form a hydrogen bond network with the polar groups of the hydrogel, and also have cationic-π interactions and hydrophobic synergy with the hydrogel; therefore, the hydrogel is indirectly bonded to the implant matrix through the polydopamine coating, so that more functional components, such as antibacterial and osteogenic factors, can play a role by being incorporated into the hydrogel.

[0034] 2. Adding Ti3C2 suspension during the preparation of the polydopamine coating of the present invention yields better results because GSH in Ti3C2 suspension can effectively reduce and protect Ti3C2; ethanol in Ti3C2 suspension reduces surface tension and promotes single-layer dispersion.

[0035] 3. In this invention, after the copper chloride solution is added dropwise, the Ti3C2 suspension is added 8-12 minutes after the reaction begins. At this time, the free radicals are in a high concentration stage and at the critical point of cross-linking. The three-dimensional network is in its infancy and has not yet solidified. The solution viscosity at this time is also conducive to the dispersion of Ti3C2, resulting in better performance. Detailed Implementation

[0036] The raw materials in this invention include the following components:

[0037] Tantalum metal powder: Medical grade spherical high-purity tantalum metal powder, purity ≥99.99wt%, 15-45μm;

[0038] Osteopathic bioceramics: Commercially available products using β-TCP bioceramics;

[0039] Magnesium β-glycerophosphate: Using commercially available product 927-20-8;

[0040] Dopamine hydrochloride: There are many types, including PEGylated dopamine, sulfonated dopamine and 3-methacryloyl dopamine, etc. This invention only uses the commercially available 3-methacryloyl dopamine product with CAS number 471915-89-6 as an example for illustration.

[0041] LAP: Lithium phenyl-2,4,6-trimethylbenzoylphosphonite, using the commercially available product with CAS number 85073-19-4;

[0042] The present invention will be further described in detail below with reference to embodiments and comparative examples.

[0043] Example 1

[0044] A method for preparing a bone-compatible dental implant includes the following steps:

[0045] Step 1: Mix 30wt% osteogenic bioceramic, 1.5wt% strontium phosphate and 1.0wt% β-glycerophosphate magnesium phosphate in 67.5wt% tantalum metal powder to obtain a mixed raw material;

[0046] Step 2: The mixed raw materials are 3D printed to obtain the implant matrix;

[0047] Step 3: Generate a polydopamine coating on the implant substrate to obtain a coated implant;

[0048] Step 4: Adhere the hydrogel to the coated implant to a thickness of 50μm to obtain the bone-friendly dental implant.

[0049] The method for preparing coated implants includes the following steps:

[0050] S1. Add the implant matrix to the dopamine hydrochloride solution (concentration 2.5 mg / mL), then add copper chloride solution dropwise (after the addition, the copper chloride concentration is 1.5 mM). After the addition is complete, start the catalytic reaction for 45 min (40-50 min is acceptable). Immediately after the copper chloride solution is added, add 0.4 wt% Ti3C2 (compare with the content of osteogenic bioceramic; for example, if 30 g of osteogenic bioceramic is added, then 0.4 g of Ti3C2 is added).

[0051] S2. After the reaction is complete, add 0.2wt% EDTA-disodium and mix for 10 min. The pH of the solution during mixing is 8.5. Remove, rinse, and dry to obtain the coated implant.

[0052] The preparation method of hydrogel includes the following steps:

[0053] 5 wt% sodium alginate, 15 wt% nanocellulose whiskers and 29.9 wt% water (to bring the total to 100 wt%) were mixed together, and then 50 wt% calcium chloride solution was added dropwise (the calcium chloride concentration in the solution was 5 wt%, so the calcium chloride accounted for 2.5 wt% in the hydrogel). After standing for 2 min, 0.1 wt% LAP was added, and the hydrogel was obtained after UV irradiation (365 nm, 60 s).

[0054] Example 2-3

[0055] Example 2, based on the preparation method of Example 1, adjusts the preparation steps in the preparation method of the coated implant:

[0056] Instead of adding 0.4wt% Ti3C2 immediately after the copper chloride solution was added, add a Ti3C2 suspension immediately after the copper chloride solution was added. The Ti3C2 suspension was obtained by adding 0.4wt% Ti3C2 and 0.2wt% GSH to a 20% ethanol solution and then mixing it by sonication.

[0057] Example 3, based on the preparation method of Example 2, adjusts the preparation steps in the preparation method of the coated implant:

[0058] Instead of adding the Ti3C2 suspension immediately after the copper chloride solution was added, add the Ti3C2 suspension 10 minutes after the copper chloride solution was added.

[0059] Comparative Example 1

[0060] Comparative Example 1, based on the preparation method of Example 1, skipped step 3 and instead bonded the hydrogel to the implant matrix with a thickness of 50 μm to obtain an osteogenic dental implant.

[0061] Performance testing

[0062] The bone-supporting dental implants of Examples 1-3 and Comparative Example 1 were subjected to the following performance tests, and the test results are shown in Table 1.

[0063] Bond strength retention rate

[0064] The bond strength retention rate of hydrogel on osseointegrated dental implants was determined according to ISO 9693:2019.

[0065] Biocompatibility

[0066] The biocompatibility, i.e., cell viability, of bone-compatible dental implants is measured according to ISO-10993:2018.

[0067] Table 1. Types and timing of Ti3C2 addition in Examples 1-3 and Comparative Example 1, along with performance testing results.

[0068]

[0069] Referring to Table 1, and comparing Examples 1-3 and Comparative Example 1, it is clear that the present invention's method of indirectly connecting the hydrogel and implant matrix together via a polydopamine coating is entirely feasible. This effectively improves the adhesion strength retention rate of the hydrogel, facilitating its full function. The reason is that the polydopamine coating, on the one hand, forms covalent bonds with tantalum metal powder through catechol groups and chelates with strontium / magnesium ions through quinone groups. On the other hand, the phenolic hydroxyl groups of the polydopamine coating form a hydrogen bond network with the polar groups of the hydrogel, and also exhibit cationic-π interactions and hydrophobic synergy with the hydrogel.

[0070] When preparing polydopamine coatings, adding a Ti3C2 suspension is more effective than adding Ti3C2 directly. This is because directly adding Ti3C2 easily leads to oxidative degradation, while the GSH in the Ti3C2 suspension effectively protects its reducing properties. Directly adding Ti3C2 also tends to cause lamellar accumulation, reducing the effective specific area, while the ethanol in the Ti3C2 suspension reduces surface tension and promotes single-layer dispersion.

[0071] The timing of adding the Ti3C2 suspension is also crucial. During the reaction period of 8-12 minutes, the free radicals are at a high concentration, the three-dimensional network is in its nascent stage, and it has not yet solidified. At this time, the solution viscosity is also favorable for Ti3C2 dispersion. Therefore, adding the Ti3C2 suspension at the beginning of the reaction (8-12 minutes) yields better results.

[0072] Examples 4-7

[0073] Examples 4-7 are based on the preparation method of Example 3, but the timing of adding Ti3C2 suspension is adjusted. The specific adjustments are shown in Table 2.

[0074] The bone-supporting dental implants of Examples 4-7 were subjected to the above performance tests, and the test results are shown in Table 2.

[0075] Table 2. Timing of Ti3C2 suspension addition and performance testing in Examples 3 and 4-7.

[0076]

[0077] Referring to Table 2, a comparison of Examples 3 and 4-7 shows that adding the Ti3C2 suspension too early can hinder molecular cyclization, resulting in insufficient cross-linking of the coating and uneven thickness. Adding the Ti3C2 suspension too late allows the polydopamine coating to gradually solidify, making it increasingly difficult for Ti3C2 to embed, and the solution also exhibits high viscosity, hindering Ti3C2 dispersion. Therefore, adding the Ti3C2 suspension 8-12 minutes after the reaction begins is more suitable.

[0078] Examples 8-9

[0079] Example 8, based on the preparation method of Example 1, adjusts the preparation steps in the preparation method of the coated implant:

[0080] S2. After the reaction is complete, add 0.2wt% EDTA-disodium and mix for 10 min. The pH of the solution during mixing is 7.0. Remove, rinse, and dry to obtain the coated implant.

[0081] Example 9, based on the preparation method of Example 1, adjusts the preparation steps in the preparation method of the coated implant:

[0082] S2. After the reaction is complete, add 0.2wt% EDTA-disodium and mix for 5 min (4-6 min) at pH 8.5 (pH 8.4-8.6 is also acceptable), then mix for 5 min (4-6 min) at pH 7.0 (pH 6.9-7.1 is also acceptable). Remove, rinse, and dry to obtain the coated implant.

[0083] The bone-supporting dental implants of Examples 8-9 were subjected to the above performance tests, and the test results are shown in Table 3.

[0084] Table 3. Reaction conditions and performance test results for Examples 1 and 8-9.

[0085]

[0086] Referring to Table 3, a comparison of Examples 1 and 8-9 shows that EDTA-disodium can efficiently chelate copper ions at pH 8.5, and can promote the exposure of amino / carboxyl active sites at pH 7.0. Stepwise treatment can achieve more beneficial effects.

[0087] Examples 10-11

[0088] Example 10 modifies the preparation method of the hydrogel based on the preparation method of Example 1, as follows:

[0089] 5 wt% sodium alginate, 15 wt% nanocellulose whiskers and 29.85 wt% water (to bring the total to 100 wt%) were mixed together, and then 50 wt% calcium chloride solution was added dropwise (the calcium chloride concentration in the solution was 5 wt%, so the calcium chloride accounted for 2.5 wt% in the hydrogel). After standing for 2 min, 0.1 wt% LAP was added and mixed for 30 s, and then 0.05 wt% sodium ascorbate was added. UV irradiation (365 nm, 60 s) was started immediately to obtain the hydrogel.

[0090] Example 11 is based on the preparation method of Example 1, but the preparation method of the hydrogel is adjusted as follows:

[0091] 5 wt% sodium alginate, 15 wt% nanocellulose whiskers and 29.85 wt% water (to bring the total to 100 wt%) were mixed together, and then 50 wt% calcium chloride solution was added dropwise (the calcium chloride concentration in the solution was 5 wt%, so the calcium chloride accounted for 2.5 wt% in the hydrogel). After standing for 2 min, 0.1 wt% LAP was added and mixed for 30 s, and then 0.05 wt% sodium ascorbate was added. After waiting for 30 s, UV irradiation (365 nm, 60 s) was started to obtain the hydrogel.

[0092] The bone-supporting dental implants of Examples 10-11 were subjected to the above performance tests, and the test results are shown in Table 4.

[0093] Table 4. Timing of UV irradiation in Examples 1 and 10-11 after the addition of sodium ascorbate and performance testing.

[0094]

[0095] Referring to Table 4, a comparison of Examples 1 and 10-11 shows that adding sodium ascorbate after mixing with LAP during hydrogel preparation yields better results. This is because sodium ascorbate can regulate free radical reduction, eliminate oxygen inhibition, and quench toxic byproducts.

[0096] However, after adding sodium ascorbate, UV irradiation is required immediately. This is because if UV irradiation is not performed after adding sodium ascorbate, free radicals will be consumed, leading to uneven UV-induced degradation.

[0097] This specific embodiment is merely an explanation of the present invention and is not intended to limit the invention. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they are within the scope of the claims of the present invention.

Claims

1. A method of producing a bone- seeking dental implant, characterized by, The method comprises the following steps: Step 1, mixing osteoactive bioactive ceramics, strontium phosphate and beta-magnesium glycerophosphate in tantalum metal powder to obtain mixed raw materials; Step 2, 3D printing the mixed raw materials to obtain an implant base; Step 3, generating a polydopamine coating on the implant base to obtain a coated implant; Step 4, bonding a hydrogel on the coated implant to obtain an osteophilic dental implant; The preparation method of the coated implant comprises the following steps: S1, adding the implant base into a dopamine hydrochloride solution, then adding a copper chloride solution dropwise to catalyze the reaction, and adding Ti3C2; S2, after the reaction is completed, adding EDTA-disodium for mixing, taking out for rinsing, and drying to obtain the coated implant; The preparation method of the hydrogel comprises the following steps: Mixing sodium alginate, nanocellulose whiskers and water together, then adding a calcium chloride solution dropwise, adding LAP, and irradiating with UV to obtain the hydrogel.

2. The method of producing a bone-seeking dental implant according to claim 1, characterized in that: In the step of S1, a Ti3C2 suspension is added; components of the Ti3C2 suspension include Ti3C2, GSH, ethanol and water.

3. The method of producing a bone-seeking dental implant according to claim 2, characterized in that: In the step of S1, after the copper chloride solution is added dropwise, the Ti3C2 suspension is added when the reaction is started for 8-12 min.

4. The method of producing a bone-seeking dental implant according to claim 1, characterized in that: In the step of S1, the reaction time of the catalytic reaction is 40-50 min.

5. The method of producing a bone-seeking dental implant according to claim 1, characterized in that: In the step of S2, the EDTA-disodium is added and mixed for 4-6 min at pH 8.4-8.6, and then mixed for 4-6 min at pH 6.9-7.

1.

6. The method of producing a bone-seeking dental implant according to claim 1, characterized in that: After the LAP is added for mixing, sodium ascorbate is added, and then UV irradiation is immediately performed to obtain the hydrogel.

7. The method of producing a bone-adhesion dental implant according to claim 1, characterized in that: Mixing sodium alginate, nanocellulose whiskers, functional components and water together, wherein the functional components include at least one of chlorhexidine microcapsules, IGF-1 microcapsules and BMP-2 analog peptide microcapsules.

8. A bone-seeking dental implant, characterized by: Prepared by the preparation method of the osteophilic dental implant in any one of claims 1-7. Prepared by the preparation method of the osteophilic dental implant in any one of claims 1-7.

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