CN116510080A - Prosthetic implant with surface coating - Google Patents

Prosthetic implant with surface coating Download PDF

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Publication number
CN116510080A
CN116510080A CN202310475061.2A CN202310475061A CN116510080A CN 116510080 A CN116510080 A CN 116510080A CN 202310475061 A CN202310475061 A CN 202310475061A CN 116510080 A CN116510080 A CN 116510080A
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China
Prior art keywords
coating
chiral
medical device
preparation
bone
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Inventor
范存义
周超
杨亮
陈帅
车顺爱
刘珅
许彬彬
季永凤
刘万军
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Shanghai Sixth Peoples Hospital
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Shanghai Sixth Peoples Hospital
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A61L27/306—Other specific inorganic materials not covered by A61L27/303 - A61L27/32
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A61L27/32—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/082—Inorganic materials
    • A61L31/086—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/082—Inorganic materials
    • A61L31/088—Other specific inorganic materials not covered by A61L31/084 or A61L31/086
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings
    • A61L2300/608—Coatings having two or more layers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to the field of organism implants, in particular to a prosthesis implant with a surface coating, wherein the surface coating is a chiral multilevel structure coating and comprises a D-configuration chiral molecule synthesized coating, a racemic D-configuration chiral molecule synthesized coating and an L-configuration chiral molecule synthesized coating; further, the chiral multilevel structure coating can be a chiral hydroxyapatite coating, a chiral tricalcium phosphate coating, a chiral calcium silicate coating and the like. The invention utilizes the chiral multi-level structure microenvironment of the natural bone tissue to effectively simulate the multi-level chiral structure microenvironment of the natural bone, improves the suitability of the natural bone with the multi-level chiral structure in the natural bone, and the synthesized coating has the multi-level chiral structure, continuous antibacterial property, good biocompatibility, and good bone ingrowth and osseointegration.

Description

Prosthetic implant with surface coating
Technical Field
The invention relates to the field of organism implants, in particular to a prosthesis implant with a surface coating.
Background
At present, many researches are carried out on the prosthesis implant, but most of the obtained prosthesis implant is made of metal materials, and the traditional medical metals comprise stainless steel, titanium alloy, ni/Ti shape memory alloy and cobalt-based alloy, and the prosthesis implant has good comprehensive mechanical properties and is widely applied to the fields of bone repair, cardiovascular diseases, dentistry and the like.
Hydroxyapatite is one of the calcium phosphate compounds, the main inorganic component of human bone and teeth. Many apatite compounds, such as hydroxyapatite, fluoroapatite, chloroapatite, carbonate apatite, have been widely used in industry, mainly as fertilizers, fluorescent substances, catalysts, absorbents, humidity sensors and materials for electronic components. In the biomedical field, hydroxyapatite has been used as an artificial bone, a tooth root, a bio-coating layer, a bio-technical material, and the like.
Therefore, coating the surface of the prosthesis implant prepared by the metal material with the hydroxyapatite coating becomes a method for modifying the prosthesis implant, for example, in Chinese patent CN109701085A, a 3D printing porous titanium stent strontium doped hydroxyapatite bioactive coating is disclosed, the osseointegration, the bone conduction and the bone induction performance of the porous titanium stent are improved, and the strontium ions doped in the coating improve the new bone ingrowth speed in the porous titanium. As another example, in chinese patent CN109183127a, a method for preparing a composite hydroxyapatite coating on the surface of magnesium alloy is disclosed, wherein the corrosion resistance and histocompatibility of magnesium alloy are improved by performing micro-arc oxidation treatment on the surface of magnesium alloy from which the oxide layer is removed, and then forming a composite hydroxyapatite coating with good interface adhesion performance on the outer surface by using dopamine-modified hydroxyapatite. However, the active electrochemical properties of magnesium and its alloys in body fluids (SBF) lead to severe corrosion, which results in a loss of mechanical integrity, impeding their wide clinical use. The non-degradable metal materials belong to biological inert materials, and after being implanted into a human body, the surfaces and hosts of the non-degradable metal materials have the defects of poor osseointegration performance, long-term stability of the implant body, easy loosening, infection and other problems to cause failure.
The existing prosthetic implant with the coating is concentrated on the aspects of improving antibacterial performance and the like by adding components or metal ions, or the preparation technology is as follows: such as arc oxidation, electrochemical deposition, hydrothermal processes, spraying, etc. But neglects the chiral multi-level structure microenvironment of the natural bone tissue, the obtained coating cannot effectively simulate the multi-level chiral structure microenvironment of the natural bone, and lacks a structure matched with the multi-level chiral structure in the natural bone. The biological material with biological suitability is a key point in the field of tissue repair, reconstruction and regeneration, and the pore, surface roughness, topological morphology and other structures of the biological material are important factors of biological adaptation. Therefore, the biological material with good adaptability and excellent performance can be prepared by regulating the structure of the material.
Disclosure of Invention
The invention adopts nontoxic and biodegradable absorbable chiral molecules as an asymmetric fracture inducer, synthesizes a chiral multilevel structure coating under the condition of gradual change from acidity to neutrality, is used for the prosthetic implant, and has better biocompatibility, bone growth and osseointegration of the prosthetic implant coated with the coating.
The coating material with the chiral multilevel structure is prepared by adding soluble chiral molecules, namely an asymmetric breakage inducer, in the preparation process, and inducing the crystal lattice of the coating material to twist or rotate in the forming process, so that the coating material with the chiral multilevel structure is formed.
The coating materials according to the invention are ceramic materials of the type which are used as specific biological or physiological functions, i.e. directly for organisms or organisms-related organismsCeramic materials for medical use, biochemistry and the like. Specifically, the method can comprise barium-based bioceramics: if BaX, X is acid radical; magnesium-based bioceramics: if MgX, X is acid radical; calcium-based bioceramics: including a variety of calcium-based ceramics such as: hydroxyapatite, beta-tricalcium phosphate, calcium silicate, calcium borate, calcium carbonate, and a variety of calcium phosphates; microcrystalline glass biological ceramics: such as CaO-Al 2 O 3 -SiO 2 、β--CaO·SiO 2 、SiO 2 -Al 2 O 3 -B 2 O 3 、SiO 2 -Al 2 O 3 -ZnO、SiO 2 -Al 2 O 3 -BaO、SiO 2 -Al 2 O 3 -Na 2 O、SiO 2 -Al 2 O 3 -K 2 O、SiO 2 -Al 2 O 3 -Fe 2 O 3 Or SiO 2 -Al 2 O 3 -Sb 2 O 3 The method comprises the steps of carrying out a first treatment on the surface of the Alumina bioceramics: alumina ceramic, activated alumina ceramic, neutral alumina ceramic, and acidic alumina ceramic; fluorapatite bioceramics: such as Ca5F (PO) 4 ) 3 The method comprises the steps of carrying out a first treatment on the surface of the Aluminosilicate bioceramics: such as olivine-island silicates, green-curtain (double tetrahedra) island silicates, tourmaline (rings of tetrahedra) cyclic silicates, pyroxene (single chain) chain silicates, amphibole (double chain) chain silicates, mica, and clay (sheet) layered silicates; oxide bioceramics: such as Al 2 O 3 ，ZrO 2 Magnesium oxide, barium oxide, silicon oxide, titanium oxide; nitride bioceramics: such as silicon nitride, boron nitride, aluminum nitride, gallium nitride, and titanium nitride; carbide bioceramics: such as titanium carbide, zirconium carbide, tungsten carbide, and silicon carbide; boride bioceramics: such as titanium boride, tantalum boride, vanadium boride, chromium boride, zirconium boride, tungsten boride, molybdenum boride, niobium boride, hafnium boride; silicide bioceramics: such as manganese silicide, iron silicide, cobalt silicide, nickel silicide, titanium silicide, zirconium silicide, niobium silicide, vanadium silicide, niobium silicide, tantalum silicide, molybdenum silicide, tungsten silicide, barium silicide, and the like.
The acid radical refers to acid radical ion, namely anion generated when acid is ionized. Including phosphate, silicate, borate, carbonate, strontium, titanate, niobate, molybdate, tungstate, manganate, ferrite, vanadate, and the like.
Chiral molecules for use in the present invention may be: chiral organic acids such as tartaric acid, malic acid, lactic acid, camphorsulfonic acid, phenylglycine, cyclohexylglycine, tranexamic acid, cis-3-aminocyclohexanoic acid, and/or ascorbic acid; chiral amino acid: such as histidine, arginine, lysine, isoleucine, phenylalanine, leucine, tryptophan, alanine, methionine, proline, cysteine, aspartic acid, valine, serine, glutamine, tyrosine, aspartic acid, glutamic acid, glutamine, and/or threonine; chiral saccharides: such as glucose, fructose, galactose, ribose, deoxyribose, furanose, pyranose, maltose, sucrose, lactose, and/or galactose; chiral alcohol: such as mannitol, xylitol, sorbitol, paclitaxel, resveratrol, ginkgo leaf polyprenol, (R) - (+) -1-phenyl-1-propanol, (S) - (-) -1-phenyl-1-propanol, amphetamine, iditol, 2-amino-1-propanol, and/or galactitol. Chiral esters: such as diethyl tartrate, and/or methyl lactate; chiral salts: such as histidinol dihydrochloride, ammonium tartrate, sodium ascorbate, carnitine hydrochloride, cysteine ethyl ester hydrochloride, sodium tartrate, and/or sodium potassium tartrate; other chiral molecules: such as microcrystalline cellulose, ammonium enzyme, glutathione, lincomycin, tetracycline, levodopamine, biphenyl, and/or spirane molecules, and the like. In one embodiment of the invention, the amount of chiral molecules added during the preparation of the bioceramics is related to the amount of positive ions added, and the amount of positive ions added: the addition amount of chiral molecules is 1:0.05-10, preferably the addition amount of cations: the addition amount of chiral molecules is 1:0.1-10, and the addition amount of cations is further preferred: the addition amount of chiral molecules is 1:0.1-5, and more preferably the addition amount of cations: the addition amount of chiral molecules is 1:0.2-5 (the addition amount ratio is the molar ratio).
In one embodiment of the invention, the preparation method of the coating material is the existing methods such as a hydrothermal reaction method, a high-temperature calcination method, a solvothermal reaction method and the like, and chiral molecules are added as an asymmetric fracture inducer in the existing preparation method process to obtain the chiral multi-stage structure coating material. (the above is directed to CN 202210171578.8)
In a first aspect, the invention provides the use of a coating having a chiral multistage structure for the preparation of a medical device.
Further, the chiral multi-stage structure coating comprises a coating synthesized by chiral molecules in a D configuration, a coating synthesized by chiral molecules in a racemic D configuration and a coating synthesized by chiral molecules in an L configuration.
Further, the chiral multi-stage structure coating preferably has an L-chiral multi-stage structure coating.
Further, the chiral multilevel structure coating can be a chiral hydroxyapatite coating, a chiral tricalcium phosphate coating, a chiral calcium silicate coating and the like.
Further, the chiral multilevel structure coating is preferably a chiral hydroxyapatite coating.
Furthermore, the thickness of the coating coated with the chiral multilevel structure on the surface of the medical instrument is 1-100um.
Furthermore, the thickness of the coating layer coated with the chiral multilevel structure on the surface of the medical instrument is preferably 5-50um.
Further, the reaction condition of coating the chiral multilevel structure coating on the surface of the medical device is 120-200 ℃.
Further, the medical device is a medical device with a coating of a chiral multistage structure on the surface.
Further, the medical device with the chiral multilevel structure coating on the surface has one or more of the following functions:
a, bone ingrowth is more;
b, has better osseointegration performance;
c, has better antibacterial property;
further, the medical device is preferably a prosthetic implant.
Further, the prosthetic implant is preferably a medical implant.
Further, the medical implants include, but are not limited to, trauma, spinal, joint, orthopedic, other materials that help support osseointegration.
Still further, the traumatic implant includes, but is not limited to, bone plates, bone screws, intramedullary nails, titanium nails, external fixation stents; the spinal implants include, but are not limited to, vertebral body implants, titanium mesh, fusion cage, and the like; the joint implant comprises, but is not limited to, an artificial hip joint, an artificial knee joint, an artificial shoulder joint, an artificial elbow joint and the like; such other implants include, but are not limited to, sports medical products, bone repair materials. In a second aspect, the present invention provides a prosthetic implant having a surface coated with a chiral multi-stage structural coating.
Further, the chiral multi-stage structure coating comprises a D chiral multi-stage structure coating, a racemic chiral multi-stage structure coating and an L chiral multi-stage structure coating.
Further, the chiral multi-stage structure coating preferably has an L-chiral multi-stage structure coating.
Further, the chiral multilevel structure coating can be a chiral hydroxyapatite coating, a chiral tricalcium phosphate coating, a chiral calcium silicate coating and the like.
Further, the chiral multilevel structure coating is preferably a chiral hydroxyapatite coating.
Further, the thickness of the coating layer of the chiral multilevel structure coated on the surface of the prosthesis implant is 1-100um.
Further, the thickness of the coating layer of the chiral multilevel structure coated on the surface of the prosthesis implant is preferably 5-50um. Further, the reaction condition of coating the surface of the prosthesis implant with the chiral multilevel structure coating is 120-200 ℃.
Further, the prosthetic implant may have one or more of the following functions:
a, bone ingrowth is more;
b, has better osseointegration performance.
Further, the prosthetic implant is preferably a medical implant.
Further, the medical implants include materials including, but not limited to, trauma, spinal, joint, and other materials that help support osseointegration.
Still further, the traumatic implant includes, but is not limited to, bone plates, bone screws, intramedullary nails, titanium nails, external fixation stents; the spinal implants include, but are not limited to, vertebral body implants, titanium mesh, fusion cage, and the like; the joint implant comprises, but is not limited to, an artificial hip joint, an artificial knee joint, an artificial shoulder joint, an artificial elbow joint and the like; such other implants include, but are not limited to, sports medical products, bone repair materials.
The chiral multi-stage coating used in the present invention is the coating used in the first and second aspects, and the chiral multi-stage coating used in the present invention may be a chiral hydroxyapatite coating, a chiral tricalcium phosphate coating, a chiral calcium silicate coating, or the like.
The chiral multilevel structure coating comprises a soluble calcium source, a soluble phosphorus source/silicon source, a chiral inducer, a complexing agent and water;
the mole ratio of the soluble calcium source, the soluble phosphorus source/silicon source, the chiral inducer, the complexing agent and the water is 1:0.6:0.1 to 3:0.5 to 3:1111 to 2223.
The mole ratio of the soluble calcium source, the soluble phosphorus source, the chiral inducer, the complexing agent and the water is preferably 1:0.6:0.5 to 1.5: 1-2: 1500-1800.
In the invention, the mole ratio of the soluble calcium source, the soluble phosphorus source, the chiral inducer, the complexing agent and the water is preferably 1:0.67:0.5 to 1.5: 1-2: 1500-1800.
In the invention, the mole ratio of the soluble calcium source, the silicon source, the chiral inducer, the complexing agent and the water is preferably 1:1:0.5 to 1.5: 1-2: 1500-1800.
The soluble calcium source of the present invention is preferably anhydrous calcium chloride, calcium nitrate tetrahydrate, calcium sulfate dihydrate, calcium oxalate and/or a combination thereof; the soluble phosphorus source is preferably diammonium phosphate, dipotassium phosphate, disodium phosphate and/or a combination thereof; the silicon source is preferably silicon dioxide;
in the preparation of the coating reaction liquid, a small amount of Zn (NO) can be added for improving the antibacterial property of the coating 3 ) 2 、AgNO 3 Etc.
Drawings
FIG. 1 shows 3 kinds of implant titanium sheets with a chiral multi-stage structure coating on the surface (A is an implant titanium sheet with a D-type chiral multi-stage structure coating, B is an implant titanium sheet with an L-type chiral multi-stage structure coating, and C is an implant titanium sheet with a racemic chiral multi-stage structure coating).
Fig. 2 is an SEM image of 3 kinds of multi-stage structure hydroxyapatite coating layers (a is an SEM image of D-type multi-stage structure hydroxyapatite coating layers, B is an SEM image of L-type multi-stage structure hydroxyapatite coating layers, and C is an SEM image of racemic multi-stage structure hydroxyapatite coating layers).
FIG. 3 is an XRD pattern of an L-type multi-level structured hydroxyapatite coating and corresponding powder.
Fig. 4 is a circular dichroism chart of a chiral multilevel structure hydroxyapatite coating.
Fig. 5 is an experimental view of implantation of titanium nails with a chiral multilevel structure hydroxyapatite coating.
FIG. 6 CT images of bone ingrowth for titanium nails with chiral multilevel hydroxyapatite coating for 4 weeks and 8 weeks.
Fig. 7 is a graph of bone ingrowth data for a titanium peg having a chiral multilevel hydroxyapatite coating (a is the relative bone volume or bone volume fraction, B is bone density, C is bone trabecular thickness, D is bone trabecular spacing).
Detailed Description
The present invention will be further described with reference to the drawings and specific embodiments, wherein the described embodiments are only some, but not all, of the embodiments of the invention. The embodiment is an actual application example, and is easily grasped and verified by those skilled in the art. If some change is made on the basis of the present invention, the substance thereof does not exceed the scope of the present invention. It should be noted that, without conflict, the embodiments of the present invention and features of the embodiments may be combined with each other.
Osseointegration is the implantation of biocompatible materials into bone, with no fibrous tissue at the interface with each other over a healing period, in complete contact with each other under light microscopy, and a very thin matrix is visible under electron microscopy. The implant and natural tooth, respectively, are that there is no periodontal ligament (PDL) present between the implant and the surrounding alveolar bone, but new bone is created, i.e. a direct bond between the artificial plant and the bone. The direct contact between the implant and the bone, abbreviated as osseointegration, is observed by an optical microscope. Can bear strength after osseointegration: and has a longer and better prognosis.
Chirality is a fundamental property of nature, is ubiquitous in living organisms, and is closely related to vital activities such as DNA, proteins, cells, tissues, and the like of various helical structures. The multi-level structure is a phenomenon commonly existing in nature, and the material has a multi-level organization structure, so that the unexpected performance is endowed to the material.
Prosthetic implants, also known as prostheses, are a type of medical device that replaces a limb, organ or tissue of the human body. Depending on the use of the prosthesis, it can be classified into an in vitro prosthesis and an implantable prosthesis. However, aseptic loosening and infection of the prosthesis implant are main reasons for treatment failure, and traditional methods such as antibacterial peptide modification, physical activation, coating and the like can only overcome single-aspect problems, so that the multifunctional coating strategy becomes an effective solution, and the existing multifunctional prosthesis coating treatment effect is still not ideal.
EXAMPLE 1 preparation of titanium sheet of chiral Multi-level Structure hydroxyapatite adaptive coating
The embodiment provides a preparation method of a prosthesis implant with a chiral multilevel structure hydroxyapatite adaptive coating, which comprises the following steps:
step S1, surface activation treatment of an implant titanium sheet: putting the cleaned titanium sheet into ethanol acetone (1:1, v/v) to be ultrasonically washed for 30 minutes; then cleaning with a large amount of ultrapure water, putting into 0.1M dilute hydrochloric acid solution, and soaking for 60min at room temperature; after the reaction, the titanium plate was washed with a large amount of ultrapure water and then vacuum-dried at 60 degrees to obtain a surface-activated titanium plate.
Step S2, preparing and optimizing a reaction solution of the chiral multilevel structure hydroxyapatite adaptive coating: selecting Ca (NO) 3 ) 2 And (NH) 4 )H 2 PO 4 The Ca/P ratio is controlled to be 1.67, and the mole ratio of the complexing agent (urea) and the chiral inducer tartaric acid (tartaric acid has three chiral structures of levorotatory, dextrorotatory and racemized) to Ca is controlled to be 1:1:1, a step of; preparing three kinds of hydroxyapatite adaptive coating reaction solutions of levorotatory, dextrorotatory and racemic according to the proportion; to improve the antibacterial property of the coating, a small amount of Zn (NO) is added in the preparation of the chiral coating reaction liquid 3 ) 2 ；
Step S3, respectively immersing the implant titanium sheet after the activation treatment into the 3 reaction liquids obtained in the step S2, fully and uniformly stirring the implant titanium sheet at the room temperature under the hydrothermal condition, packaging the implant titanium sheet in a hydrothermal reaction kettle, and reacting for 24 hours at 180 ℃;
and S4, after the reaction is finished, naturally cooling, taking out the implant titanium sheet with the surface coating, alternately cleaning with a large amount of ultrapure water and absolute ethyl alcohol, and finally drying under vacuum at 60 ℃ overnight to obtain 3 titanium sheets with the coating.
The results are shown in FIG. 1-FIG. 4, FIG. 1 shows 3 kinds of implant titanium sheets with chiral multilevel structure coating on the surface (A is implant titanium sheet with D-type chiral multilevel structure coating, B is implant titanium sheet with L-type chiral multilevel structure coating, C is implant titanium sheet with racemic chiral multilevel structure coating); FIG. 2 is an SEM image of 3 kinds of multi-stage structure hydroxyapatite coating layers (A is an SEM image of D-type multi-stage structure hydroxyapatite coating layers, B is an SEM image of L-type multi-stage structure hydroxyapatite coating layers, and C is an SEM image of racemic multi-stage structure hydroxyapatite coating layers); FIG. 3 is an XRD pattern of L-type and D-type multi-stage structure hydroxyapatite coating layers and corresponding powders (A is an XRD pattern of L-type multi-stage structure hydroxyapatite coating layers and corresponding powders, B is an XRD pattern of D-type multi-stage structure hydroxyapatite coating layers and corresponding powders); FIG. 4 is a circular dichroism chart of 3 kinds of chiral multistage-structured hydroxyapatite coating (A is a circular dichroism chart of a D-type chiral multistage-structured hydroxyapatite coating, B is a circular dichroism chart of an L-type chiral multistage-structured hydroxyapatite coating, and C is a circular dichroism chart of a racemic chiral multistage-structured hydroxyapatite coating)
The experimental results show that:
as shown in fig. 1, the implant titanium sheet of the present example 1 has a chiral multi-stage structural coating on the surface thereof;
as shown in fig. 2, the SEM image of the L-type multi-stage structure hydroxyapatite coating layer of the present example 1 has a microstructure in the shape of a staggered and aligned sheet, has a uniform surface morphology, and exhibits a multi-stage chiral structure;
as shown in fig. 3, the SEM image of the D-type multi-stage structure hydroxyapatite coating layer of the present example 1 has a microstructure in the shape of a staggered and aligned sheet, has a uniform surface morphology, and exhibits a multi-stage chiral structure;
as shown in fig. 4, the XRD patterns of the chiral multi-structured hydroxyapatite coating layer and the corresponding powder of the present example 1 show characteristic peaks of hydroxyapatite crystals;
as shown in fig. 5, the chiral multi-structure hydroxyapatite coating layers of this example 1 all showed circular dichroism, indicating that the hydroxyapatite coating layers synthesized with the left-handed tartaric acid molecules and the right-handed tartaric acid molecules all formed chiral mesostructures and had the corresponding optical characteristics, and the hydroxyapatite coating layers synthesized with the racemic tartaric acid molecules did not have the optical activity.
Example 2 preparation of titanium sheet of chiral Multi-stage tricalcium phosphate adaptive coating
The embodiment provides a preparation method of a prosthesis implant with a chiral multi-stage tricalcium phosphate adaptive coating, which comprises the following steps:
step S1, surface activation treatment of an implant titanium sheet: putting the cleaned titanium sheet into ethanol acetone (1:1, v/v) to be ultrasonically washed for 30 minutes; then cleaning with a large amount of ultrapure water, putting into 0.1M dilute hydrochloric acid solution, and soaking for 60min at room temperature; after the reaction, the titanium plate was washed with a large amount of ultrapure water and then vacuum-dried at 60 degrees to obtain a surface-activated titanium plate.
S2, preparing and optimizing a chiral multi-stage structure tricalcium phosphate adaptive coating reaction solution: selecting CaCl 2 And (NH) 4 )H 2 PO 4 The Ca/P ratio is controlled to be 1.5, and the mole ratio of the complexing agent (urea) and the chiral inducer (malic acid) to Ca is controlled to be 1:1:1, preparing three tricalcium phosphate adaptive coating reaction solutions of levorotatory, dextrorotatory and racemic respectively according to the proportion; in order to improve the antibacterial property of the coating, a small amount of AgNO is added in the preparation of the chiral coating reaction liquid 3 。
Step S3, immersing the implant titanium sheet after the activation treatment into a reaction liquid to react under the hydrothermal condition: immersing the activated titanium sheet into the reaction liquid, fully and uniformly stirring at room temperature, packaging in a hydrothermal reaction kettle, and reacting for 8 hours at 140 ℃;
and S4, after the reaction is finished, naturally cooling, taking out the implant titanium sheet with the surface coating, alternately cleaning with a large amount of ultrapure water and absolute ethyl alcohol, and finally drying under vacuum at 60 ℃ overnight to obtain the titanium sheet with the chiral multi-stage structure tricalcium phosphate coating.
Example 3 preparation of chiral Multi-stage calcium silicate adaptive coating titanium sheet
The embodiment provides a preparation method of a prosthesis implant with a chiral multi-stage structure calcium silicate adaptive coating, which comprises the following steps:
step S1, surface activation treatment of an implant titanium sheet: putting the cleaned titanium sheet into ethanol acetone (1:1, v/v) to be ultrasonically washed for 30 minutes; then cleaning with a large amount of ultrapure water, putting into 0.1M dilute hydrochloric acid solution, and soaking for 60min at room temperature; after the reaction, the titanium plate was washed with a large amount of ultrapure water and then vacuum-dried at 60 degrees to obtain a surface-activated titanium plate.
Step S2, preparing and optimizing a chiral multi-stage structure calcium silicate adaptive coating reaction solution: selecting CaCl 2 And SiO 2 The Ca/Si ratio is controlled to be 1, the mole ratio of the complexing agent (urea) and the chiral inducer (glutamic acid) to Ca is controlled to be 1:1:1, a step of; preparing three kinds of calcium silicate adaptive coating reaction solutions of levorotatory, dextrorotatory and racemic according to the proportion; in order to improve the antibacterial property of the coating, a small amount of AgNO can be added in the preparation of the chiral coating reaction liquid 3 。
Step S3, immersing the implant titanium sheet after the activation treatment into a reaction liquid to react under the hydrothermal condition: immersing the activated titanium sheet into the reaction liquid, fully and uniformly stirring at room temperature, packaging in a hydrothermal reaction kettle, and reacting for 20 hours at 160 ℃;
and S4, after the reaction is finished, naturally cooling, taking out the implant titanium sheet with the surface coating, alternately cleaning with a large amount of ultrapure water and absolute ethyl alcohol, and finally drying under vacuum at 60 ℃ overnight to obtain the titanium sheet with the chiral multi-stage structure calcium silicate coating.
Example 4 preparation of a titanium nail with a chiral Multi-level hydroxyapatite adaptive coating
The embodiment provides a preparation method of a titanium nail with a chiral multilevel structure hydroxyapatite adaptive coating, which comprises the following steps:
step S1, surface activation treatment of implant titanium nails: placing the cleaned titanium nails into ethanol acetone (1:1, v/v) to ultrasonically wash for 30 minutes; then cleaning with a large amount of ultrapure water, putting into 0.1M dilute hydrochloric acid solution, and soaking for 60min at room temperature; after the reaction, the titanium nails are washed by a large amount of ultrapure water and then vacuum dried at 60 ℃ to obtain the titanium nails with activated surfaces.
Step S2, preparing and optimizing a reaction solution of the chiral multilevel structure hydroxyapatite adaptive coating: selecting Ca (NO) 3 ) 2 And (NH) 4 )H 2 PO 4 The Ca/P ratio is controlled to be 1.67, and the mole ratio of the complexing agent (urea) and the chiral inducer (tartaric acid) to Ca is controlled to be 1:1:1, respectively preparing three hydroxyapatite adaptive coating reaction solutions of levorotatory, dextrorotatory and racemic according to the proportion; to improve the antibacterial property of the coating, a small amount of Zn (NO) is added in the preparation of the chiral coating reaction liquid 3 ) 2 。
Step S2, immersing the implant titanium nails after the activation treatment into a reaction liquid to react under the hydrothermal condition: immersing activated titanium nails in the reaction liquid, fully and uniformly stirring at room temperature, packaging in a hydrothermal reaction kettle, and reacting for 24 hours at 180 ℃;
and S4, after the reaction is finished, naturally cooling, taking out the implant titanium sheet with the surface coating, alternately cleaning with a large amount of ultrapure water and absolute ethyl alcohol, and finally drying in vacuum at 60 ℃ overnight to obtain the titanium nail with the chiral multilevel structure hydroxyapatite layer.
Example 5 application of chiral multistage hydroxyapatite adaptive coating to titanium nails
Step S1, sterilizing the titanium nails of the chiral multilevel structure hydroxyapatite adaptive coating prepared in the embodiment 4;
s2, performing modeling on the femur of the rabbit;
step S3, implanting the titanium nails in the step 1 on the femur of the rabbit in the molding;
step S4, taking out samples at different time points of the 4 th week and the 8 th week, and fixedly analyzing the bone ingrowth and osseointegration effects;
as shown in fig. 5, a photograph of a titanium peg implanted in a femur of a rabbit (see fig. 5);
the results show that the bone in-growth around the coated titanium nail was more excellent at week 8 than the uncoated titanium nail; compared with the non-chiral hydroxyapatite coating, the bone ingrowth amount around the titanium nails with the D chiral multilevel structure coating, the L chiral multilevel structure coating and the racemized chiral multilevel structure coating is obviously increased, and the L chiral multilevel structure coating HAs better bone ingrowth and osseointegration performance (see the CT image of the bone ingrowth of the titanium nails of fig. 6 for 4 weeks and 8 weeks; the Ti group is the titanium nails with the general coating, the HA group is the titanium nails without the coating, the L-CHA group is the titanium nails with the L chiral multilevel structure coating, the D-CHA group is the titanium nails with the D chiral multilevel structure coating, and the Rac-CHA group is the titanium nails with the racemized chiral multilevel structure coating).
Further CT quantification data shows (see FIG. 7. Bone in-growth quantification data graph of titanium nails, A is relative bone volume or bone volume fraction, B is bone density, C is bone trabecular thickness, D is bone trabecular spacing), and the bone mass around titanium nails with L chiral multi-stage structural coating is higher than other groups, regardless of 4 weeks or 8 weeks, further demonstrating that L chiral multi-stage structural coating is more beneficial for bone in-growth and osseointegration.
In the experiment, compared with the titanium nails without the coating, the bone ingrowth effect around the titanium nails with the coating is better, and the bone ingrowth is better at the 8 th week; compared with the coating without chiral hydroxyapatite, the coating with the D chiral multilevel structure, the coating with the L chiral multilevel structure and the coating with the raceme chiral multilevel structure have better bone ingrowth effect around the titanium nail, wherein the coating with the L chiral multilevel structure has more obvious bone ingrowth and bone integration performances.

Claims (10)

1. Use of a coating having a chiral multi-stage structure comprising a coating synthesized from chiral molecules in the D configuration, a coating synthesized from chiral molecules in the racemic D configuration and a coating synthesized from chiral molecules in the L configuration for the preparation of a medical device.
2. The use of a coating having a chiral multi-stage structure according to claim 1 for the preparation of a medical device, wherein the chiral multi-stage structure coating comprises a chiral hydroxyapatite coating, a chiral tricalcium phosphate coating, a chiral calcium silicate coating.
3. The use of a coating having a chiral multistage structure according to claim 1 for the preparation of a medical device, wherein the thickness of the coating applied to the surface of the medical device is 1um to 100um.
4. Use of a coating with a chiral multistage structure according to claim 1 for the preparation of a medical device, wherein the thickness of the coating applied to the surface of the medical device is preferably between 5um and 50um.
5. The use of a coating having a chiral multistage structure according to claim 1 for the preparation of a medical device, wherein the reaction conditions for coating the surface of the medical device with the coating having a chiral multistage structure are 120 ℃ to 200 ℃.
6. Use of a coating having a chiral multistage structure according to claim 1 for the preparation of a medical device comprising a prosthetic implant having one or more of the following functions:
a, bone ingrowth is more;
b, has better osseointegration performance;
and C, the antibacterial performance is better.
7. Use of a coating having a chiral multistage structure according to claim 5 for the preparation of a medical device, wherein the prosthetic implant is preferably a medical implant comprising a trauma, spinal, joint, orthopedic, other material that helps support osseointegration.
8. The use of a coating having a chiral multistage structure according to claim 5 for the preparation of medical devices, wherein said traumatic implants include, but are not limited to, bone plates, bone screws, intramedullary nails, titanium nails, external fixation stents; the spinal implants include, but are not limited to, vertebral body implants, titanium mesh, fusion cage, and the like; the joint implant comprises, but is not limited to, an artificial hip joint, an artificial knee joint, an artificial shoulder joint, an artificial elbow joint and the like; such other implants include, but are not limited to, sports medical products, bone repair materials.
9. A prosthetic implant coated with a coating of a chiral multi-stage structure according to claim 1.
10. The prosthetic implant coated with a chiral multi-stage structural coating on a surface of claim 9, wherein the prosthetic implant has one or more of the following functions:
a, bone ingrowth is more;
b, has better osseointegration performance.
CN202310475061.2A 2023-04-28 2023-04-28 Prosthetic implant with surface coating Pending CN116510080A (en)

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