Oral implant abutment with gingival healing promoting and immune regulation effects and preparation method thereof

By constructing the PSBMA-PEG-LDP coating on the surface of the titanium implant abutment, the problem of poor bioseality of the implant abutment at the gingival interface is solved, and long-acting biocompatibility and immune regulation of the implant abutment-gingival interface is achieved, promoting gingival healing and implant long-term stability.

CN119455088AActive Publication Date: 2025-02-18FOURTH MILITARY MEDICAL UNIVERSITY
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Patent Information

Application Number
CN202411572863.6
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-06
Publication Date
2025-02-18
Estimated Expiration
2044-11-06

AI Technical Summary

Technical Problem

The existing titanium implant abutment has poor biological enclosure at the gingival interface and is susceptible to pathogenic microorganisms, resulting in gingival inflammation and failure of implant surgery.

Method used

The hydrated buffer layer was formed by using proteoglycan-like thiobetaine polymer molecular brushes (PSBMA) and LDP (Laminin-5α3-derived adhesion peptide) was covalently linked to LDP (Laminin-5α3-derived adhesion peptide) through the PEG structure to construct stable PSBMA-PEG-LDP Coating, modified planting abutment surface.

Benefits of technology

Long-acting biocompatibility and immune regulation of the implant abutment-gingival interface are achieved, promoting gingival epithelial closure and healing, and improving the long-term stability of the implant.

✦ Generated by Eureka AI based on patent content.

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Abstract

The invention provides an oral implant abutment with gingival healing promoting and immunoregulation effects and a preparation method thereof, and belongs to the technical field of novel oral implants.The problem that the implant-gingival interface sealing performance is poor is solved.The preparation method comprises the steps that 1, pure titanium is selected to be processed into the abutment, and cleaning and drying are conducted; 2, synthesizing a polydopamine mediated coating on the surface of the abutment processed in the step 1; step 3, constructing a (3-trimethoxy) propyl 2-bromo-2-methyl propionate initiator coating on the surface of the abutment obtained in the step 2; step 4, constructing a PSBMA-PEG polymer coating on the surface of the abutment obtained in the step 3; and step 5, constructing a PSBMA-PEG-LDP coating on the surface of the abutment obtained in the step 4. The functional group of PSBMA-PEG is covalently connected with LDP to form a stable PSBMA-PEG-LDP specific coating on the surface of the implant abutment, so that the long-acting effect of LDP on the implant abutment-gingival interface is realized, and a new hope is brought to effective combination of the implant abutment and gingiva.
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Description

Technical Field

[0001] The present invention belongs to the technical field of oral implantation, and in particular relates to an oral implantation base having both gum healing-promoting and immune-regulating functions and a preparation method thereof. Background Art

[0002] As my country enters an aging society and the public pays more and more attention to oral health, people's demand for implants to repair missing teeth to improve their quality of life continues to increase. However, the implant abutments commonly used in clinical practice are mechanically smooth, and the biological closure of the implant abutment-gingival interface is poor, which is easily invaded and destroyed by pathogenic microorganisms, causing peri-implant gingival inflammation. In recent years, people have become increasingly aware of the importance of good gingival healing around the implant abutment and the immune phenotype that promotes tissue healing for maintaining the long-term stability of the implant. Surface modification of titanium implant abutments to improve the closure of the implant abutment-gingival interface has gradually become a hot topic in related basic and clinical research. However, existing research based on changing the surface structure and surface morphology of the implant abutment has not yet achieved ideal restoration effects.

[0003] Titanium and titanium alloy implants have excellent biocompatibility, corrosion resistance, chemical stability and mechanical strength. They have been widely used in clinical practice to repair missing teeth and prepare maxillofacial prosthetic retainers. However, whether the implant can survive for a long time depends not only on its combination with bone tissue, but also on the healing of the gingival soft tissue around the implant abutment. Compared with natural teeth, the gingival tissue around the implant abutment lacks vertical collagen fibers, has fewer blood vessels, and poor adhesion of the gingival junctional epithelium. Therefore, it is impossible to form a tight gingival seal, which is easy to cause gingival inflammation around the implant abutment and lead to implant surgery failure. Therefore, forming a tight biological seal at the implant abutment-gingival interface is crucial to maintain the long-term stability of the implant. The gingival interface around the implant abutment is composed of two regions: epithelium and connective tissue. Among them, the attachment of the gingival junctional epithelium to the surface of the implant abutment is the key to the formation of gingival seal. However, histological studies have found that the implant abutment-gingival junctional epithelium interface lacks hemidesmosomes (HDs) structure and the inner base plate structure in the upper 2 / 3 of the interface is incomplete. Laminin-5 is an important protein derived from the cell basement membrane, which plays an important role in promoting the nucleation of HDs assembly and maintaining the structural stability of HDs. Studies have shown that the lack of Laminin-5 is an important reason for the incomplete structure of HDs and the inner substrate at the gingival interface around the implant abutment.

[0004] With the progress of implant surface treatment technology, more and more researchers have devoted themselves to the special design of implant abutment surface bio-coating modification in recent years to promote gingival healing around the implant abutment.

[0005] Laminin-5 is used to prepare a drug-loaded coating on the surface of the implant base, and the local release of Laminin-5 at the implant base-gingival interface is achieved, which brings new hope for promoting the formation of gingival epithelial closure and effective healing of the implant base-gingiva. However, the direct use of Laminin-5 for surface modification of the implant base has disadvantages such as high immunogenicity and easy inactivation of large molecular proteins. With the further deepening of the research, researchers have found that the subunits and polypeptide sequences derived from Laminin-5 have a strong effect of promoting cell adhesion and gingival closure, especially the Laminin-5α3 chain (LAMA3) derived adhesion peptides (LAMA3-derivedpeptides, LDP), which have high stability and low immunogenicity, and can better meet the needs of clinical applications. The inventors previously constructed a plasmid / chitosan / type IV collagen sustained-release coating expressing the LDP sequence on the surface of the implant base based on gene transfection, and a series of in vitro and in vivo experiments confirmed that the coating has the effect of promoting gingival epithelial cell adhesion and gingival epithelial closure. However, the bonding force between the above coating and the base substrate is weak, and it is easy to fall off during the implantation process; and the LDP obtained by expressing the target gene using genetic engineering technology is easily degraded by proteases.

[0006] Polymer molecular brushes refer to a special polymer assembly structure formed by fixing one end of a high-density polymer molecular chain on a certain interface or surface and freeing the other end. When the molecular chains are very close and the density is large enough, due to the steric hindrance effect, most of the free ends extend in the direction perpendicular to the substrate, forming a "brush"-like structure. Compared with other surface modification methods (such as silanization), polymer molecular brushes can increase the spatial density of different numbers of functional groups on the surface, thereby allowing more biomolecules to be connected. By introducing functional polar monomers into its surface for chemical modification, the purpose of improving the hydrophilicity, biocompatibility, and corrosion resistance of the material can be further achieved. There are two main ways to connect molecular brushes to substrate materials: physical adsorption and covalent grafting. Molecular brushes prepared by physical adsorption are too sensitive to changes in temperature and solvent. Atom transfer radical polymerization (ATRP) not only has more relaxed requirements on experimental conditions, but also can actively and controllably adjust the surface thickness of polymer molecular brushes, and can also synthesize polymers with functionalized end groups to meet the special application requirements of different clinical materials. Therefore, introducing functional polymer molecular brushes into the surface design of implant bases will bring new hope for constructing stable LDP modified coatings. The main disadvantage of existing polymer molecular brush technology is that the experimental conditions are relatively harsh, which increases the complexity and cost of the operation. Summary of the invention

[0007] In view of the above problems, the present invention uses a proteoglycan-like sulfobetaine polymer molecular brush (polysulfobetaine methacrylate, PSBMA) to adsorb a large amount of water molecules to form a hydrated buffer layer, thereby having a good ability to withstand the external pressure and compression, shear and tensile forces of the load. Through the rich functional group structure of PEG, the chemical modification requirements are met, and LDP is covalently linked to form a stable PSBMA-PEG-LDP coating, which is used to perform biological modification of the implant base and achieve peri-implant gingival healing.

[0008] The technical solution adopted by the present invention is:

[0009] In a first aspect, the present invention provides a method for preparing an oral implant abutment having both gum healing promoting and immune regulation effects, comprising the following steps:

[0010] Step 1: Select pure titanium to be processed into a base, and then clean and dry it;

[0011] Step 2: synthesizing a polydopamine-mediated coating on the surface of the base processed in step 1;

[0012] Step 3: constructing a (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator coating on the surface of the base obtained in step 2;

[0013] Step 4: constructing a PSBMA-PEG polymer coating on the surface of the base obtained in step 3;

[0014] Step 5: Construct a PSBMA-PEG-LDP coating on the surface of the base obtained in step 4.

[0015] In some embodiments, the specific operation of step 2 is as follows:

[0016] Immerse the pure titanium base in Tris-HCl solution with a pH value of 8.5, shake the reaction solution in a 27°C water bath for 4 hours, take it out and rinse the surface with a large amount of ultrapure water, and use it after natural drying.

[0017] In some embodiments, the concentration of dopamine hydrochloride in the Tris-HCl solution is 2 mg / mL.

[0018] In some embodiments, the specific operations of step 3 are as follows:

[0019] The dried substrate with the polydopamine-mediated coating was immersed in a mixture of 50% PBS and ethanol containing (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator, the pH value of the 50% PBS solution was 8.5, and the reaction solution was shaken in a 32°C water bath for 12 hours to prepare the (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator coating. After taking it out, the excess initiator on the surface was rinsed with 75% ethanol and used after natural drying.

[0020] In some embodiments, the concentration of (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator in 50% PBS solution is 2 mg / mL.

[0021] In some embodiments, the specific operations of step 4 are as follows:

[0022] Step 401: preparing a reaction solution;

[0023] Step 402: immersing the substrate having the (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator coating into the reaction solution, sealing the reaction container and shaking the reaction at 50° C. for 5 hours;

[0024] Step 403: After the reaction is completed, the base is taken out, rinsed with water, and dried naturally for later use.

[0025] In some embodiments, the PBS solution with a PSBMA monomer concentration of 15 mg / mL, a COOH-PEG-acrylate concentration of 12 mg / mL, an L-ascorbic acid concentration of 2 mg / mL, a copper bromide concentration of 0.0036 mg / mL, and a 2,2'-bipyridine concentration of 0.0152 mg / mL has a pH of 7.4.

[0026] In some embodiments, the specific operations of step 5 are as follows:

[0027] The PSBMA-PEG-coated substrate was immersed in a PBS buffer containing an activator, pH 7.4, and activated at 50°C for 1 hour. After activation, the substrate was immediately transferred to a 1 mg / mL LDP solution and continued to react with LDP at 37°C for 6 hours for grafting reaction. After the reaction was completed, the reaction sample was rinsed with PBS and dried in an argon stream for later use.

[0028] In some embodiments, the activator formulation includes 0.1 mg / mL of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and 0.1 mg / mL of N-hydroxysuccinimide.

[0029] In a second aspect, the present invention provides an oral implant abutment having both gum healing-promoting and immune-regulating effects, and the abutment is prepared using a method for preparing an oral implant abutment.

[0030] Beneficial effects of the present invention:

[0031] 1. The present invention firstly develops a super hydrophilic molecular brush PSBMA-PEG, and utilizes the functional groups of PSBMA-PEG to covalently link LDP to form a stable PSBMA-PEG-LDP specific coating on the surface of the implant base, thereby achieving the long-term effect of LDP at the implant base-gingival interface.

[0032] 2. The PSBMA-PEG-LDP specific coating constructed by the present invention can promote the polarization of macrophages to the M2 phenotype that inhibits inflammatory response, thereby achieving immune regulation.

[0033] 3. The PSBMA-PEG-LDP specific coating constructed in the present invention has the effect of promoting the closure formation of gingival epithelium in animals. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0035] Figure 1 The morphology of the PSBMA-PEG-LDP coating prepared on the surface of the pure titanium implant abutment (SEM image);

[0036] Figure 2 The morphology of the PSBMA-PEG-LDP coating prepared on the surface of the pure titanium implant abutment (atomic force microscopy image);

[0037] Figure 3 The morphology of cells on the surface of dental implant abutments after preparing PSBMA-PEG-LDP coating on the surface of pure titanium implant abutments (SEM image);

[0038] Figure 4 The early adhesion of cells on the surface of dental implant abutments after PSBMA-PEG-LDP coating was prepared on the surface of pure titanium implant abutments (laser confocal microscopy image);

[0039] Figure 5 To investigate the expression of cell adhesion-related gene LAMA3 after preparing PSBMA-PEG-LDP coating on the surface of pure titanium implant abutment;

[0040] Figure 6To investigate the expression of cell adhesion-related protein Laminin-5α3 after preparing PSBMA-PEG-LDP coating on the surface of pure titanium implant abutment;

[0041] Figure 7 To investigate the expression of CD206, a gene related to macrophage immune regulation, after PSBMA-PEG-LDP coating was prepared on the surface of pure titanium implant abutments;

[0042] Figure 8 The formation of hemidesmosomes in the gingival epithelial cells around the prepared dental implant abutment after it was implanted into the animal's maxillary bone (transmission electron microscopy image). DETAILED DESCRIPTION

[0043] In order to make the purpose, technical solution and advantages of the embodiments of the present invention more clear, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention.

[0044] Polymer molecular brushes refer to a special polymer assembly structure formed by fixing one end of a high-density polymer molecular chain on a certain interface or surface and freeing the other end. When the molecular chains are very close and the density is large enough, due to the steric hindrance effect, most of the free ends extend in the direction perpendicular to the substrate, forming a "brush"-like structure. Compared with other surface modification methods (such as silanization), polymer molecular brushes can increase the spatial density of different numbers of functional groups on the surface, thereby allowing more biomolecules to be connected. By introducing functional polar monomers into its surface for chemical modification, the purpose of improving the hydrophilicity, biocompatibility, and corrosion resistance of the material can be further achieved. There are two main ways to connect molecular brushes to substrate materials: physical adsorption and covalent grafting. Molecular brushes prepared by physical adsorption are too sensitive to changes in temperature and solvent. Atom transfer radical polymerization (ATRP) not only has more relaxed requirements on experimental conditions, but also can actively and controllably adjust the surface thickness of polymer molecular brushes, and can also synthesize polymers with functionalized end groups to meet the special application requirements of different clinical materials. Therefore, introducing functionalized polymer molecular brushes into the surface design of implant abutments will bring new hope for constructing stable LDP-modified coatings.

[0045] Example 1

[0046] This embodiment specifically provides a method for preparing an oral implant abutment having both gum healing promoting and immune regulation effects, comprising the following steps:

[0047] Step 1: Select pure titanium to be processed into a base, and ultrasonically clean it with acetone, anhydrous ethanol and ultrapure water for 15 minutes in sequence, and dry it naturally.

[0048] Step 2: Use the super strong adhesion between dopamine and titanium substrate to synthesize surface initiators. The specific steps are as follows: immerse the pure titanium base in a Tris-HCl solution (pH 8.5) with a dopamine hydrochloride concentration of 2 mg / mL, shake the reaction solution in a 27°C water bath for 4 hours, take it out and rinse the surface with a large amount of ultrapure water, and use it after natural drying.

[0049] Step 3: Constructing (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator coating: Immerse the polydopamine-mediated coating substrate dried in the previous step in a mixed solvent of 50% PBS (pH 8.5) and ethanol with a (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator concentration of 2 mg / mL, and shake the reaction solution in a 32°C water bath for 12 hours to prepare the (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator coating. After taking it out, rinse the excess initiator on the surface with 75% ethanol and use it after natural drying.

[0050] Step 4: Constructing PSBMA-PEG polymer coating: First, prepare the reaction solution with the following formula: PBS (pH 7.4) solution with a PSBMA monomer concentration of 15 mg / mL, COOH-PEG-acrylate concentration of 12 mg / mL, L-ascorbic acid concentration of 2 mg / mL, copper bromide concentration of 0.0036 mg / mL, and 2,2'-bipyridine concentration of 0.0152 mg / mL.

[0051] The (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator coated substrate was immersed in the reaction solution, and the reaction container was sealed and shaken at 50°C for 5 hours. After the reaction was completed, the substrate was taken out, rinsed with pure water, and dried naturally for use.

[0052] Step 5: Construction of PSBMA-PEG-LDP coating: The PSBMA-PEG coated substrate was immersed in PBS buffer (pH 7.4) containing an activator, the activator formula of which was 0.1 mg / mL of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and 0.1 mg / mL of N-hydroxysuccinimide.

[0053] The activation reaction was carried out at 50°C for 1 hour to ensure effective functionalization of the substrate surface. After activation, the coated substrate was immediately transferred to a 1 mg / mL LDP solution and continued to react with LDP at 37°C for 6 hours for grafting reaction. After the reaction was completed, the reaction sample was rinsed with PBS and dried in an argon stream for later use.

[0054] Example 2

[0055] This example mainly characterizes the PSBMA-PEG-LDP coated implant base prepared in Example 1 and conducts relevant functional experiments.

[0056] (1) The surface morphology of the PSBMA-PEG-LDP coated implant abutment was observed by scanning electron microscopy: the PSBMA-PEG-LDP coated implant abutment was dehydrated with 30%, 50%, 70%, 80%, 90%, and 100% ethanol in a gradient manner, vacuum dried, and then sprayed with gold; the surface morphology of the PSBMA-PEG-LDP coated implant abutment was observed by scanning electron microscopy. The results are shown in Figure 1 , a uniformly deposited PSBMA-PEG-LDP coating can be observed on the surface of the PSBMA-PEG-LDP coated implant abutment, and a small amount of polydopamine nanoparticles can be seen.

[0057] (2) Observation of the surface morphology of PSBMA-PEG-LDP coated implant abutments using atomic force microscopy: The surface morphology of PSBMA-PEG-LDP coated implant abutments was observed using atomic force microscopy, and 3D reconstruction images were collected. Figure 2 , a uniformly deposited PSBMA-PEG-LDP coating can be observed on the surface of the PSBMA-PEG-LDP coated implant abutment.

[0058] (3) Cell seeding experiment to detect the biocompatibility of PSBMA-PEG-LDP coated implant abutments:

[0059] (i) Preparation of cell suspension: When human epithelial cells have grown to 80% of the bottom area of ​​the cell culture flask, digest and centrifuge to prepare a cell suspension; (ii) Place the PSBMA-PEG-LDP coated planting base in a 48-well cell culture plate and inoculate 5×10 cells per well. 4 epithelial cells; (iii) add cell culture medium and continue culturing in a CO2 incubator for 2 hours, remove the PSBMA-PEG-LDP coated implant base in the 48-well plate, rinse twice with PBS buffer; fix in 4% paraformaldehyde for 12 hours; (iv) rinse twice with PBS buffer, dehydrate the base with 30%, 50%, 70%, 80%, 90% and 100% ethanol gradient, then use hexamethyldisilazane chemical dehydration, vacuum dry and spray gold; use scanning electron microscopy to observe the morphology of cells on the surface of the base. Results are shown in Figure 3 Under a scanning electron microscope, after 2 hours of culture, the cells on the surface of the PSBMA-PEG-LDP coated planting base had obvious filopodia formation, indicating that the planting base of the present invention has good cell compatibility.

[0060] (4) Cell adhesion test to detect the biocompatibility of PSBMA-PEG-LDP coated implant base: The PSBMA-PEG-LDP coated implant base was placed in a 48-well cell culture plate. The cells were digested and centrifuged at 5×10 4The cells were inoculated onto the surface of the planting platform at a density of 100 cells / well and cultured for 4 hours. The cells were rinsed 3 times with PBS buffer to remove the non-adherent cells. The cells were fixed with 4% paraformaldehyde for 30 minutes, the nuclei were stained with DAPI, and the slides were sealed with 50% glycerol. The cells were observed and photographed using a laser confocal microscope. Figure 4 Under a laser confocal microscope, a large number of adherent and growing cells can be seen, indicating that the planting base of the present invention has good cell compatibility.

[0061] (5) RT-qPCR experiment to detect the expression level of LAMA3, an epithelial cell adhesion-related gene, on the surface of PSBMA-PEG-LDP coated implant base: PSBMA-PEG-LDP coated implant base was placed in a 48-well cell culture plate. After digestion and centrifugation, the cells were concentrated to 5×10 4 The cells were inoculated onto the surface of the planting platform at a density of 100 cells / well and cultured for 3 days. Total RNA was extracted, reverse transcribed to synthesize cDNAs, and polymerase chain reaction was used to amplify cDNAs. Figure 5 Compared with the control group, the cells on the surface of the PSBMA-PEG-LDP coated implant base expressed higher levels of LAMA3, indicating that the implant base of the present invention has the effect of promoting the expression of adhesion-related genes.

[0062] Western Blot experiment was used to detect the expression level of Laminin-5α3, an adhesion-related protein of epithelial cells, on the surface of PSBMA-PEG-LDP-coated implant base: PSBMA-PEG-LDP-coated implant base was placed in a 6-well cell culture plate. 5 Cells were inoculated onto the surface of the planting platform at a density of 100 cells / well and cultured for 3 days. Cell lysis buffer was added to extract protein, and the protein concentration was determined by BCA method. Western Blot was used to detect the expression level of Laminin-5α3. Figure 6 Compared with the control group, the cells on the surface of the PSBMA-PEG-LDP coated implant base expressed higher levels of Laminin-5α3, indicating that the implant base of the present invention has the effect of promoting the expression of adhesion-related proteins.

[0063] (7) RT-qPCR experiment to detect the expression of macrophage immune regulation-related gene CD206 on the surface of PSBMA-PEG-LDP coated implant base: PSBMA-PEG-LDP coated implant base was placed in a 48-well cell culture plate. Then macrophages were cultured at 5×10 4 The cells were inoculated onto the surface of the planting platform at a density of 100 cells / well and cultured for 3 days. Total RNA was extracted, reverse transcribed to synthesize cDNAs, and polymerase chain reaction was used to amplify cDNAs. Figure 7Compared with the control group, the cells on the surface of the PSBMA-PEG-LDP coated implant base expressed higher levels of CD206, indicating that the implant base of the present invention has the effect of promoting the polarization of macrophages in the M2 direction.

[0064] (8) Rat mandibular implantation experiment to detect the formation of hemidesmosomes in gingival epithelial cells around the implant base: (i) Animal experiment and sampling: After the animals were anesthetized, the oral cavity was disinfected; the right maxillary first molar was extracted, and an implant cavity was prepared in the mesial alveolar fossa, and a pure titanium implant and a PSBMA-PEG-LDP-coated implant base were immediately implanted; after 4 weeks of feeding, the samples were collected and the gingival tissue around the implant base was cut with a sharp blade to make a 2 mm 3 The tissue blocks were fixed with 4% glutaraldehyde solution. (ii) Transmission electron microscopy observation of the formation of hemidesmosomes: The gingival tissue blocks were embedded in resin, ultrathinly sectioned and stained to observe the formation of hemidesmosomes. Figure 8 Under transmission electron microscopy, it can be observed that the gingival epithelial cells around the PSBMA-PEG-LDP coated implant base form obvious electron-dense spots, which are hemidesmosome structures closely related to cell adhesion, indicating that the implant base of the present invention can promote gingival epithelial closure in animals.

[0065] result:

[0066] The PSBMA-PEG-LDP coated implant base prepared by the present invention has good biocompatibility; has the function of promoting the expression of adhesion-related genes and proteins; has an immunomodulatory effect and can promote the polarization of macrophages toward the M2 direction; and has the function of promoting the closure of the gingival epithelium in animals.

[0067] The embodiments described above are only preferred specific implementation modes of the present invention, and the protection scope of the present invention is not limited thereto. Any simple changes or equivalent replacements of the technical solutions that can be obviously obtained by any technician familiar with the field within the technical scope disclosed in the present invention belong to the protection scope of the present invention.

Claims

1. A method for preparing an oral implant abutment having both gum healing promoting and immune regulation effects, characterized in that: The following steps are involved: Step 1: Select pure titanium to be processed into a base, and then clean and dry it; Step 2: synthesizing a polydopamine-mediated coating on the surface of the base processed in step 1; Step 3: constructing a (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator coating on the surface of the base obtained in step 2; Step 4: constructing a PSBMA-PEG polymer coating on the surface of the base obtained in step 3; Step 5: Construct a PSBMA-PEG-LDP coating on the surface of the base obtained in step 4.

2. The oral implant abutment having both gum healing promoting and immune regulation effects and the preparation method thereof according to claim 1, characterized in that: The specific operations of step 2 are as follows: Immerse the pure titanium base in Tris-HCl solution with a pH value of 8.5, shake the reaction solution in a 27°C water bath for 4 hours, take it out and rinse the surface with a large amount of ultrapure water, and use it after natural drying.

3. The oral implant abutment having both gum healing promoting and immune regulation effects and the preparation method thereof according to claim 2, characterized in that: The concentration of dopamine hydrochloride in the Tris-HCl solution is 2 mg / mL.

4. The oral implant abutment having both gum healing promoting and immune regulation effects and the preparation method thereof according to claim 1, characterized in that: The specific operations of step 3 are as follows: The dried substrate with the polydopamine-mediated coating was immersed in a mixture of 50% PBS and ethanol containing (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator, the pH value of the 50% PBS solution was 8.5, and the reaction solution was shaken in a 32°C water bath for 12 hours to prepare the (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator coating. After taking it out, the excess initiator on the surface was rinsed with 75% ethanol and used after natural drying.

5. The oral implant abutment having both gum healing promoting and immune regulation effects and the preparation method thereof according to claim 4, characterized in that: The concentration of (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator in 50% PBS solution was 2 mg / mL.

6. The oral implant abutment having both gum healing promoting and immune regulation effects and the preparation method thereof according to claim 1, characterized in that: The specific operations of step 4 are as follows: Step 401: preparing a reaction solution; Step 402: immersing the substrate having the (3-trimethoxy)propyl 2-bromo-2-methylpropionate initiator coating into the reaction solution, sealing the reaction container and shaking the reaction at 50° C. for 5 hours; Step 403: After the reaction is completed, the base is taken out, rinsed with water, and dried naturally for later use.

7. The oral implant abutment having both gum healing promoting and immune regulation effects and the preparation method thereof according to claim 6, characterized in that: The formula of the reaction solution prepared in step 401 is: The PBS solution has a PSBMA monomer concentration of 15 mg / mL, a COOH-PEG-acrylate concentration of 12 mg / mL, an L-ascorbic acid concentration of 2 mg / mL, a copper bromide concentration of 0.0036 mg / mL, and a 2,2'-bipyridine concentration of 0.0152 mg / mL, and a pH value of 7.

4.

8. The oral implant abutment having both gum healing promoting and immune regulation effects and the preparation method thereof according to claim 1, characterized in that: The specific operations of step 5 are as follows: The base with PSBMA-PEG coating was immersed in PBS buffer containing activator with a pH value of 7.4, and an activation reaction was carried out at 50°C for 1 hour. After the activation was completed, the base was immediately transferred to a 1 mg / mL LDP solution and continued to react with LDP at 37°C for 6 hours for grafting reaction. After the reaction was completed, the reaction sample was rinsed with PBS and dried in an argon stream for later use.

9. The oral implant abutment having both gum healing promoting and immune regulation effects and the preparation method thereof according to claim 8, characterized in that: The activator formulation included 0.1 mg / mL of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and 0.1 mg / mL of N-hydroxysuccinimide.

10. An oral implant base having both gum healing promoting and immune regulation effects, characterized in that: The base is prepared by the method according to any one of claims 1 to 9.

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