Biocompatible protective coating layers on medical implant components and methods of making same

Abstract

The invention relates to a biocompatible protective coating layer on a medical implant component and a method of making the same. In particular, the present disclosure relates to medical implant components comprising a biocompatible protective coating layer (BPCL) and methods of making the BPCL and medical implant components.

Description

Technical Field

[0001] The present disclosure relates to biocompatible protective coating layers on medical implant components and methods of making the same. In particular, the present disclosure relates to a biocompatible protective coating layer (BPCL), preferably silicon nitride (SiN x ) layer medical implant component and BPCL and method for manufacturing the medical implant component. Background Art

[0002] Medical implant components can be used in a variety of clinical and healthcare applications to provide benefits to physicians, surgeons, registered professional nurses and patients during or after medical treatment. Thanks to advances in materials science and medical science, the prognosis for patients who need surgery or medical implants is becoming increasingly better. For example, artificial joints can improve motor function and extend the duration of a body part of an individual or patient suffering from an age-related condition or disease.

[0003] In order to enhance the effectiveness of medical implants, coatings may be applied to their surfaces. However, existing coated medical implants may still exhibit certain defects or shortcomings, such as insufficient biocompatibility, durability or strength. In addition, the cost of existing methods for preparing coated medical implants may still be high, and the applicability of the methods may be limited in view of the materials of the medical implants.

[0004] Therefore, there is still a need to develop novel and cost-effective medical implants and methods for preparing the same. Summary of the invention

[0005] Accordingly, the present disclosure relates to a medical implant assembly comprising:

[0006] (a) a biocompatible substrate, and

[0007] (b) a biocompatible protective coating layer (BPCL) disposed above or on the substrate;

[0008] wherein the biocompatible substrate is made of one or more materials selected from the group consisting of: a biocompatible polymeric material, a biocompatible metal or alloy, and a biocompatible ceramic, and

[0009] The biocompatible protective coating layer (BPCL) has a porosity of less than 1.5%, preferably 1% or less.

[0010] The present disclosure also relates to a method for manufacturing a medical implant component as described herein, comprising the following steps:

[0011] (i) providing a biocompatible substrate in a deposition chamber;

[0012] (ii) reducing the pressure in the deposition chamber to less than 0.75 Torr; and

[0013] (iii) depositing a biocompatible protective coating layer material over or on the substrate to form the biocompatible protective layer.

[0014] In one aspect, the present disclosure provides a medical implant component comprising a biocompatible substrate, a buffer layer on the substrate, and a biocompatible protective coating layer on the buffer layer, that is, the buffer layer is located between the biocompatible substrate and the biocompatible protective coating layer, wherein the buffer layer is made of an oxide, nitride or carbide of any one of the following elements: silicon (Si), aluminum (Al), zirconium (Zr) and boron (B).

[0015] In one aspect, the present disclosure provides a method for manufacturing a medical implant component as described herein, comprising the following steps:

[0016] (i) providing a biocompatible substrate in a deposition chamber;

[0017] (ii) reducing the pressure in the deposition chamber to less than 0.75 Torr;

[0018] (ii') depositing a buffer layer material selected from the group consisting of oxides, nitrides or carbides of any one of the following elements to form a buffer layer on the substrate; and

[0019] (iii') depositing a material of a biocompatible protective coating layer to form the biocompatible protective coating layer on the buffer layer.

[0020] In one aspect, the present disclosure provides the medical implant component as part or all of an artificial joint, part or all of an insert associated with an artificial joint, or part or all of a temporary anchoring device.

[0021] In one aspect, the present disclosure provides a medical implant component characterized by comprising a biocompatible protective coating layer (BPCL) and optionally a buffer layer as described herein.

[0022] In one embodiment, the biocompatible protective coating layer has a thickness of 0.5 μm to 70 μm, preferably 5 to 30 μm.

[0023] In any of the aforementioned embodiments, the biocompatible protective coating layer (BPCL) has a hardness (Vickers hardness) of at least 800 HV, preferably at most 900 HV, more preferably at most 1200 HV, and most preferably at most 1400 HV.

[0024] In any of the aforementioned embodiments, the biocompatible protective coating layer (BPCL) has a surface roughness of less than 0.25 μm, preferably 0.2 μm or less.

[0025] In any of the foregoing embodiments, the stoichiometry of the atoms of the biocompatible protective coating layer (BPCL) material varies by less than 20%.

[0026] In any of the aforementioned embodiments, the biocompatible protective coating layer (BPCL) is formed of particles having a D50 in the range of 0.1 μm to 10 μm, preferably in the range of 0.5 μm to 3 μm.

[0027] In any of the aforementioned embodiments, the coefficient of kinetic friction between the medical implant component and other corresponding medical components (such as a liner or insert) is in the range of 0.07 to 0.7, preferably 0.08 to 0.65, and more preferably 0.1 to 0.55.

[0028] In any of the aforementioned embodiments, the biocompatible polymeric material is selected from the group consisting of polytetrafluoroethylene (PTFE), polyetheretherketone (PEEK), polyethylene (PE), polyurethane (PU), and polyvinyl chloride (PVC).

[0029] In any of the aforementioned embodiments, the PE is low-density polyethylene (LDPE), high-density polyethylene (HDPE) or ultra-high molecular weight polyethylene (UHMWPE).

[0030] In any of the foregoing embodiments, the biocompatible polymer material has a hardness of at least 400 HV (Vickers hardness), preferably at most 600 HV, and more preferably at most 1000 HV; or a Shore D (Shore hardness) of at least 50, preferably at least 55 Shore D, more preferably at least 60 Shore D, and most preferably at least 65 Shore D.

[0031] In any of the aforementioned embodiments, the biocompatible metal or alloy is selected from the group consisting of: titanium (Ti) or its alloys, zirconium (Zr) or its alloys, tantalum (Ta) or its alloys, niobium (Nb) or its alloys, stainless steel, cobalt-chromium-molybdenum (Co-Cr-Mo) alloy and Ti-6Al-4V alloy.

[0032] In any of the aforementioned embodiments, the biocompatible ceramic is selected from the group consisting of oxides, carbides, nitrides, or nitro-carbides of any of the following elements: silicon (Si), titanium (Ti), tantalum (Ta), tungsten (W), zirconium (Zr), niobium (Nb), chromium (Cr), and aluminum (Al).

[0033] In any of the aforementioned embodiments, the buffer layer has a thickness of 0.5 μm to 10 μm, preferably at least 1 μm.

[0034] In any of the aforementioned embodiments, the adhesion between the buffer layer and the substrate is at least 18 MPa, preferably at least 20 MPa, more preferably at least 25 MPa, and most preferably at least 30 MPa. The adhesion can be measured by a scratch method, Rockwell C tests, or ASTM-C1624.

[0035] In any of the aforementioned embodiments, the deposition of the buffer layer is achieved via AD, physical vapor deposition (PVD), or chemical vapor deposition (CVD).

[0036] In any of the aforementioned embodiments, the AD is performed using a carrier gas selected from the group consisting of: N2, O2, Ar, He, clean dry air (CDA), and any combination thereof.

[0037] In any of the aforementioned embodiments, the AD is performed at a flow rate of the carrier gas of 180 to 2400 l / hr, preferably 300 to 1500 l / hr.

[0038] In any of the aforementioned embodiments, the temperature of the substrate during the deposition of the buffer layer and / or the biocompatible protective coating layer (BPCL) is in the range of 5°C to 50°C, such as at least 15°C, preferably not higher than 35°C. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 An illustrative scheme showing a method of manufacturing a medical implant of the present invention.

[0040] Figure 2 An exemplary article (knee joint and screw) is shown.

[0041] FIG. 3A to FIG. 3C Demonstrate the microscopic behavior and characteristics of medical implants.

[0042] 4A to 4D Optical or SEM images of medical implants shown after wear testing.

[0043] FIG. 5A to FIG. 5C The SEM images of the screws of the present invention after wear testing are shown. DETAILED DESCRIPTION

[0044] To facilitate understanding of the disclosure herein, the terms used herein are hereby defined below.

[0045] In the context of this specification and the scope of the patent application, unless otherwise specifically indicated, the singular forms "a / an" and "the" include plural referents. Unless otherwise specified, any and all examples or exemplary language (e.g., "such as") provided herein are only used to better illustrate the present invention, rather than to limit the scope of the present invention.

[0046] It should be understood that any numerical range described in this specification is intended to include all sub-ranges contained therein. For example, the range from "50 to 70°C" includes all sub-ranges and specific values ​​between the stated minimum value of 50°C and the stated maximum value of 70°C, including, for example, from 58°C to 67°C and from 53°C to 62°C, 60°C or 68°C. Since the disclosed numerical range is continuous, it contains each value between the minimum and maximum values. Unless otherwise specified, the multiple numerical ranges indicated in this specification are approximate values.

[0047] In this disclosure, the term "about" refers to an acceptable deviation from a given value measured by one of ordinary skill in the art depending in part on how the value is measured or determined.

[0048] In the present disclosure, the material of the biocompatible protective coating layer includes materials with anti-wear / anti-abrasion properties, including but not limited to ceramics such as aluminum oxide, silicon nitride, metal nitrides, and any combination thereof, such as silicon nitride (e.g., SiN x , Si3N4), aluminum oxide (such as Al2O3), and metal nitrides (such as TiN).

[0049] In this disclosure, the term "silicon nitride" refers to a x " material, where x is a value within a reasonable range based on chemical bonding theory.

[0050] In the present disclosure, the term "biocompatible" or "biocompatibility" means being able to come into contact with a living system without causing adverse effects, such as (severe) allergic reactions, damage to cells, tissues or organs in the living body, etc.

[0051] In this disclosure, the term "porosity" refers to the level of pores in a material.

[0052] In the present disclosure, the term "dynamic coefficient of friction" is the ratio of the friction force, which can be measured, for example, by a scratch test, to the normal force experienced by a body moving over a dry, non-smooth surface.

[0053] In this disclosure, the term "aerosol deposition" refers to a deposition method in which aerosol particles collect or deposit themselves on a solid surface, reducing the concentration of particles in the air.

[0054] Medical Implant Components

[0055] Medical implants may involve metals or alloys (such as CoCrMo, Ti-6Al-4V) or polymeric materials (such as PEEK, UHMWPE) as substrate materials. During long-term use, biochemical corrosion and / or mechanical wear and stress shielding effects of the materials may lead to side effects such as poisoning, allergic reactions, peripheral tissue degeneration, etc. In addition, the hydrophobicity of certain substrate materials will adversely affect the prognosis.

[0056] To alleviate these disadvantages, it is believed that certain materials such as aluminum oxide (Al2O3), Si3N4, titanium nitride (TiN) exhibit excellent mechanical properties, chemical inertness and biocompatibility and can be used as anti-wear layers or coatings on substrate materials. However, if the protective layer has high porosity, weak adhesion and / or high surface roughness, it can easily fall off, and the particles generated thereby can cause dislocation or higher wear of the relative parts of the implant.

[0057] Therefore, in the present disclosure, the medical implant component includes a biocompatible substrate and a biocompatible protective coating layer (BPCL) above or on the substrate. In one aspect, the medical implant component includes a biocompatible substrate, a buffer layer on the substrate, and a biocompatible protective coating layer (BPCL) on the buffer layer. The biocompatible protective coating layer (BPCL) has low porosity, high adhesion, and low surface roughness. The details of the components in the medical implant component are described below.

[0058] Biocompatible substrates

[0059] In the present disclosure, biocompatible substrates known in the art may be used once they have desired characteristics, such as sufficient mechanical strength (hardness, firmness, etc.), chemical inertness, biocompatibility, etc. For example, the material used to make the biocompatible substrate may have a hardness of at least 400 HV (Vickers hardness) or a Shore D (Shore hardness) of at least 50. In various embodiments, the biocompatible substrate may be made of one or more materials selected from the group consisting of: a biocompatible polymeric material, a biocompatible metal or alloy, and a biocompatible ceramic.

[0060] Examples of biocompatible polymeric materials include, but are not limited to, polyketones, such as polyetheretherketone (PEEK); (halogenated) polyolefins, such as polyethylene (PE), poly(ethylene-propylene), polytetrafluoroethylene (PTFE), and polyvinyl chloride (PVC); polyurethanes, etc. In various embodiments, PE is low-density polyethylene (LDPE), high-density polyethylene (HDPE), or ultra-high molecular weight polyethylene (UHMWPE).

[0061] Examples of biocompatible metals or alloys include, but are not limited to, titanium (Ti) or its alloys, zirconium (Zr) or its alloys, tantalum (Ta) or its alloys, niobium (Nb) or its alloys, stainless steel, cobalt-chromium-molybdenum (Co-Cr-Mo) alloys, and Ti-6Al-4V alloys.

[0062] Examples of biocompatible ceramics include, but are not limited to, oxides, carbides, nitrides, or nitro-carbides of any of the following elements: silicon (Si), titanium (Ti), tantalum (Ta), tungsten (W), zirconium (Zr), niobium (Nb), chromium (Cr), and aluminum (Al).

[0063] In one embodiment, the biocompatible substrate has a surface roughness (Ra) less than 0.3 μm or greater than 0.01 μm. In one embodiment, the biocompatible substrate has a surface roughness (Ra) less than 0.3 μm or greater than 0.01 μm. -6 Up to 18*10 -5 Range of linear thermal expansion coefficient.

[0064] Biocompatible protective coating layer (BPCL)

[0065] In the present disclosure, the biocompatible protective coating layer (BPCL) is located on or above the substrate (for example, when there is a buffer layer described below). The biocompatible protective coating layer (BPCL) should have a porosity of less than 1.5%, preferably less than 1.3%, and more preferably less than 1%, so that the medical implant can show excellent effects, such as good durability, anti-wear effect, low friction, etc. The low porosity of this layer can be achieved by, for example, the method for manufacturing the medical implant described herein.

[0066] In one embodiment, the biocompatible protective coating layer (BPCL) has a thickness of 0.5 μm to 70 μm, for example, at least 0.5 μm, at least 1 μm, at least 2 μm, at least 3 μm, at least 4 μm, at least 5 μm, at least 6 μm, at least 7 μm, at least 8 μm, at least 9 μm, at least 10 μm, at least 11 μm, at least 12 μm, at least 13 μm, at least 14 μm, at least 15 μm, at least 20 μm, at least 25 μm, at least 30 μm, at least 35 μm; or at most 70 μm, at most 65 μm, at most 60 μm, at most 55 μm, at most 50 μm, at most 45 μm, at most 40 μm; or any reasonable numerical range consisting of the above values ​​as terminal points, for example, a thickness of 0.5 μm to 30 μm, 40 μm to 55 μm, 5 μm to 8 μm, etc.

[0067] In one embodiment, the biocompatible protective coating layer (BPCL) has a hardness (Vickers hardness) of 800HV to 1400HV, for example, at least 850HV, at least 900HV, at least 950HV, at least 1000HV, at least 1050HV, at least 1100HV; or a hardness (Vickers hardness) of at most 1350HV, at most 1300HV, at most 1250HV, at most 1200HV, at most 1150HV, at most 1100HV; or any reasonable numerical range consisting of the above values ​​as terminal points, for example, a hardness (Vickers hardness) of 900HV to 1200HV, 1150HV to 1350HV, 800HV to 1000HV, etc.

[0068] In one embodiment, the difference between the hardness of the materials of the biocompatible substrate and the biocompatible protective coating layer (BPCL) may be less than 900 HV, for example, less than 800 HV, less than 700 HV, less than 600 HV, less than 500 HV, less than 400 HV, less than 300 HV, less than 200 HV, less than 100 HV, less than 50 HV, etc.

[0069] In one embodiment, the biocompatible protective coating layer (BPCL) has a surface roughness of less than 0.25 μm, such as less than 0.2 μm, less than 0.15 μm, etc. Without being bound by theory, when the surface roughness of the biocompatible protective coating layer (BPCL) is low, the friction between the medical implant and the contact site may become low.

[0070] In one embodiment, the coefficient of kinetic friction between a medical implant component (specifically a BPCL) and another corresponding medical component (such as a pad or an insert) is in the range of 0.08 to 0.7, for example, less than 0.7, less than 0.65, less than 0.6, less than 0.55, less than 0.5, less than 0.45, less than 0.4, less than 0.3, less than 0.2, less than 0.1; or any reasonable numerical range consisting of the above values ​​as terminal points, for example, 0.1 to 0.65, 0.1 to 0.55, etc.

[0071] The average molar ratio between metal atoms and non-metal atoms (i.e., Al / O, Si / N, Ti / N) of the biocompatible protective coating layer (BPCL) can be within a reasonable range based on chemical bonding theory, and the molar ratio deviates from the perfect stoichiometry of the material (e.g., about 0.67 for aluminum oxide, about 0.75 for silicon nitride, about 1 for titanium nitride, etc.) by no more than 20%.

[0072] In one embodiment, the biocompatible protective coating layer (BPCL) is formed of particles having a D50 in the range of 0.1 μm to 10 μm, for example, about 0.2 μm, about 0.3 μm, about 0.4 μm, about 0.5 μm, about 0.6 μm, about 0.7 μm, about 0.8 μm, about 0.9 μm, about 1 μm, about 1.5 μm, about 2 μm, about 2.5 μm, about 3 μm, about 3.5 μm, about 4 μm, about 4.5 μm, about 5 μm, about 5.5 μm, about 6 μm, about 6.5 μm, about 7 μm, about 8 μm, about 9 μm, about 10 μm; or any reasonable numerical range consisting of the above values ​​as terminal points, for example, a D50 of 0.5 μm to 3 μm, 0.8 μm to 5 μm, etc.

[0073] In one embodiment, the biocompatible protective coating layer (BPCL) has a thickness of 3*10 -6 ℃ -1 Up to 15*10 -6 ℃ -1 In one embodiment, the difference between the biocompatible protective coating layer (BPCL) and the biocompatible substrate is less than 1.1*10 -6 Up to 18*10 -5 range.

[0074] In one embodiment, the biocompatible protective coating layer (BPCL) has an adhesion of at least 18 MPa to the biocompatible substrate, such as at least 19 MPa, at least 20 MPa, at least 21 MPa, at least 22 MPa, at least 23 MPa, at least 24 MPa, at least 25 MPa, at least 26 MPa, at least 27 MPa, at least 28 MPa, or any reasonable range of values ​​consisting of the above values ​​as end points, such as an adhesion of 20 MPa to 28 MPa, etc. The adhesion can be measured by a scratch test, a Rockwell C test, or ASTM-C1624.

[0075] Buffer layer

[0076] In one aspect, the medical implant component further comprises a buffer layer, which is located on the substrate and between the biocompatible substrate and the biocompatible protective coating layer (BPCL). The buffer layer can assist the adhesion between the biocompatible substrate and the biocompatible protective coating layer (BPCL). In addition, the buffer layer can allow the surface to exhibit a lower roughness compared to a planar biocompatible substrate.

[0077] Examples of materials for forming the buffer layer include, but are not limited to, oxides, nitrides, or carbides of any one of the following elements: silicon (Si), aluminum (Al), zirconium (Zr), and boron (B).

[0078] In one embodiment, the buffer layer has a thickness of 0.5μm to 10μm, for example, at least 0.5μm, at least 0.75μm, at least 1μm, at least 1.5μm, at least 2μm, at least 2.5μm, at least 3μm, at least 3.5μm, at least 4μm, at least 4.5μm, at least 5μm; or a thickness of at most 10μm, at most 9.5μm, at most 9μm, at most 8.5μm, at most 8μm, at most 7.5μm, at most 7μm, at most 6.5μm, at most 6μm, at most 5.5μm, at most 5μm; or any reasonable numerical range consisting of the above values ​​as terminal points, for example, a thickness of 1μm to 1.5μm, 7μm to 7.5μm, 2μm to 6μm, etc.

[0079] In one embodiment, the buffer layer has an adhesion of at least 18 MPa to the biocompatible substrate, such as at least 19 MPa, at least 20 MPa, at least 21 MPa, at least 22 MPa, at least 23 MPa, at least 24 MPa, at least 25 MPa, at least 26 MPa, at least 27 MPa, at least 28 MPa; or any reasonable range of values ​​formed by the above values ​​as end points, such as 20 MPa to 28 MPa, etc. In one embodiment, the buffer layer has an adhesion of at least 18 MPa to the biocompatible protective coating layer (BPCL), such as at least 19 MPa, at least 20 MPa, at least 21 MPa, at least 22 MPa, at least 23 MPa, at least 24 MPa, at least 25 MPa, at least 26 MPa, at least 27 MPa, at least 28 MPa; or any reasonable range of values ​​formed by the above values ​​as end points, such as 20 MPa to 28 MPa, etc. Adhesion can be measured by scratch test, Rockwell C test or ASTM-C1624.

[0080] Applications of Medical Implant Components

[0081] Due to excellent properties (including but not limited to good durability, good anti-wear, high density, low roughness, low porosity, good biocompatibility, etc.), the medical implant assembly can be used in various applications. Examples of applications include but are not limited to the entirety or a portion of an artificial joint (e.g., a knee replacement, a hip replacement, a shoulder replacement, a radiocarpal replacement; a cup, a head, a stem, etc.), an insert or temporary anchoring device associated with an artificial joint (e.g., for orthodontics, surgery, etc., such as a medical locking plate).

[0082] Method for manufacturing medical implant components

[0083] Conventional methods for making coatings or layers on substrates of medical implant components include plasma spraying, physical vapor deposition (PVD), chemical vapor deposition (CVD), spraying methods (hot or cold spraying), sintering methods, etc. The present inventors have found that using aerosol deposition (AD) to deposit specific ceramic materials to form a biocompatible protective coating layer (BPCL) will be beneficial in extending the life of the implant.

[0084] In brief, the AD method can exhibit the following advantages in manufacturing the medical implant components described herein: (1) the deposition rate is higher than that of the PVD / CVD method, which has the benefit of increasing production efficiency; (2) the temperature for carrying out the method for depositing the biocompatible protective coating layer (BPCL) can be significantly lower (e.g., close to room temperature) than the temperature for PVD / CVD (e.g., higher than 300° C. and even up to 800° C.), thermal spraying or cold spraying (about 300° C.) methods; (3) the vacuum requirements are less restrictive than the vacuum requirements for carrying out the PVD / CVD method; (4 ) The method can be more easily scaled up compared to the PVD / CVD method; (5) the thickness of the layer can be easily adjusted and can be larger; (6) the adhesion of the deposited layer is significantly higher than the adhesion obtained by PVD / CVD, thermal spray or cold spray methods; (7) the density and consistency of the deposited layer can be higher than the density and consistency obtained by thermal spray or cold spray methods; (8) the deposited layer or coating can be in a nearly net-like shape, which is difficult when using PVD / CVD, thermal spray or cold spray methods; and (9) the cost can be significantly lower than the cost of PVD / CVD, thermal spray or cold spray methods.

[0085] In particular, the coating layer can be obtained by the plasma spraying method generally used for surface treatment; however, the porosity is too high, the adhesion may be weak and the surface roughness is also high. The sintered coating layer can be dense and have a smooth surface; however, further processing, shaping and polishing may be difficult; additional problems (such as damage to semi-finished products or heterogeneity of the crystalline phase) may arise when the process is scaled up in view of changes in processing parameters. The PVD / CVD method is mature in this technical field and can provide coating layers with good characteristics; however, the cost is relatively high and there are inherent limitations, such as the limited thickness of the deposited layer (for example, up to about 15 μm), degradation of the substrate material due to high processing temperatures, etc. In addition, the moderate adhesion of the coating layer obtained by the PVD / CVD method may not be sufficient to prevent its wear, thus generating particles on the coating layer.

[0086] The present inventors have surprisingly discovered that the AD method is advantageous for manufacturing medical implant components, in particular biocompatible protective coating layers (BPCLs).

[0087] Therefore, the present disclosure also relates to a method for manufacturing a medical implant component as described herein, comprising the following steps:

[0088] (i) providing a biocompatible substrate in a deposition chamber;

[0089] (ii) reducing the pressure in the deposition chamber to less than 0.75 Torr; and

[0090] (iii) depositing a material of a biocompatible protective coating layer via aerosol deposition (AD) to form a biocompatible protective coating layer (BPCL) over or on the substrate.

[0091] In one aspect, the present disclosure relates to a method of manufacturing a medical implant component as described herein, comprising the steps of:

[0092] (i) providing a biocompatible substrate in a deposition chamber;

[0093] (ii) reducing the pressure in the deposition chamber to less than 0.75 Torr;

[0094] (ii') depositing a buffer layer material selected from the group consisting of oxides, nitrides or carbides of any one of the following elements to form a buffer layer on the substrate; and

[0095] (iii') depositing a material of a biocompatible protective coating layer via aerosol deposition (AD) to form a biocompatible protective coating layer (BPCL) on the buffer layer.

[0096] The biocompatible substrate may be a biocompatible substrate described herein. In one embodiment, the biocompatible substrate is made of one or more materials selected from the group consisting of: a biocompatible polymeric material, a biocompatible metal or alloy, and a biocompatible ceramic. In one embodiment, the biocompatible polymeric material is selected from the group consisting of: polyetheretherketone (PEEK), polyethylene (PE), and polyvinyl chloride (PVC). In one embodiment, PE is low-density polyethylene (LDPE), high-density polyethylene (HDPE), or ultra-high molecular weight polyethylene (UHMWPE).

[0097] The AD method can be performed by known means and equipment. The equipment for performing the AD method may include an aerosol generating unit (comprising, for example, one or more sources of one or more carrier gases, a mass flow controller (MFC), an aerosol generating chamber), a deposition chamber (equipped with, for example, a nozzle / atomizer, a support plate or stage, etc.), and a vacuum system (e.g., a pump).

[0098] Various parameters of the AD method can be adjusted. Examples of parameters include, but are not limited to, the type of one or more carrier gases; flow rate; distance between the nozzle and the substrate support; angle of incidence of the aerosol stream on the substrate; vacuum level in the deposition chamber; concentration, particle size, type of one or more materials of the biocompatible protective coating layer in the aerosol stream; temperature in the chamber; temperature of the substrate, etc.

[0099] Examples of the one or more carrier gases include, but are not limited to, nitrogen (N2), oxygen (O2), argon (Ar), helium (He), clean dry air (CDA), and any combination and ratio thereof. The flow rate of the carrier gas may be 180 to 2400 l / hr, for example, about 200 l / hr, about 250 l / hr, about 300 l / hr, about 350 l / hr, about 400 l / hr, about 450 l / hr, about 500 l / hr, about 550 l / hr, about 600 l / hr, about 650 l / hr, about 700 l / hr, about 750 l / hr, about 800 l / hr, about 850 l / hr, about 900 l / hr, about 950 l / hr, about 1000 l / hr, about 1100 l / hr, about 1200 l / hr, about 1300 l / hr, about 1400 l / hr, about 1500 l / hr, about 1600 l / hr, about 1700 l / hr, about 1800 l / hr, about 1900 l / hr, about 2000 l / hr, about 2100 l / hr, about 2300 l / hr, about 2400 l / hr, about 2500 l / hr, about 2600 l / hr, about 2700 l / hr, about 2800 l / hr, about 2900 l / hr, about 3000 l / hr, about 3500 l / hr, about 3600 l / hr, about 3700 l / hr, about 3800 l / hr, about 3900 l / hr, about 4000 l / hr, about 4100 l / hr, about 4200 l / hr, about 4300 l / hr or any reasonable numerical range consisting of the above values ​​as terminal points, for example, 500 to 650 l / hr, 300 to 1500 l / hr, etc.

[0100] The temperature (of the biocompatible substrate) during the AD method may be controlled in the range of 5°C to 50°C, such as 15°C to 45°C, preferably not higher than 35°C.

[0101] The material powder may have a D50 in the range of 0.5 μm to 10 μm, for example, about 0.2 μm, about 0.3 μm, about 0.4 μm, about 0.5 μm, about 0.6 μm, about 0.7 μm, about 0.8 μm, about 0.9 μm, about 1 μm, about 1.5 μm, about 2 μm, about 2.5 μm, about 3 μm, about 3.5 μm, about 4 μm, about 4.5 μm, about 5 μm, about 5.5 μm, about 6 μm, about 6.5 μm, about 7 μm, about 8 μm, about 9 μm, about 10 μm, or any reasonable range of values ​​consisting of the above values ​​as terminal points, for example, 0.5 μm to 3 μm, 0.8 μm to 5 μm, etc. The raw materials may be subjected to one or more pretreatments, such as milling, sieving, etc., to provide one or more materials for deposition via an AD method.

[0102] The buffer layer may be deposited via the AD method described herein or a physical vapor deposition (PVD) or chemical vapor deposition (CVD) method. Examples of PVD / CVD methods include, but are not limited to, sputtering PVD (using a DC or RF sputterer), laser-assisted PVD (LA-PVD), low pressure CVD (LPCVD), metal organic CVD (MOCVD), plasma enhanced CVD (PECVD), etc. Preferably, the buffer layer is produced via an AD method.

[0103] Once the deposition of the biocompatible protective coating layer (BPCL) is completed, the semi-finished product may be subjected to post-processing, such as cleaning, shaping, etc.

[0104] Examples

[0105] The following examples are provided to make it easier for those skilled in the art to understand the present invention, but are not intended to limit the scope of the present invention.

[0106] Materials, methods, and test models

[0107] Materials for the biocompatible protective layer include Si3N4, Al2O3, TiN (4N purity) available from Sigma-Aldrich, and CoCrMo alloy available from DePuy Synthes.

[0108] If necessary, the material can be further processed by UPE-Celanese GUR@1020-E.

[0109] The porosity of the layer can be measured by Hitachi S-4300FE-SEM. The thickness and roughness can be measured by KLA-D500. The adhesion can be evaluated by Helmut-fisher Adhesion Tester ST30 or Mitutoyo HR600 (Rockwell C indenter).

[0110] Example 1

[0111] CoCrMo alloy is used as substrate material and is cleaned and washed to remove impurities and then dried before being placed on a support in the chamber of the AD device. The temperature, vacuum and other necessary parameters are set. The material powders (i.e., aluminum, silicon nitride, titanium nitride) are loaded into the aerosol generating unit. Then, AD deposition of the material is started. After the deposition of the biocompatible protective coating layer (BPCL) is completed, the vacuum is broken and the semi-finished product is post-processed to obtain an exemplary medical implant component. Images of exemplary products (knee joints, screws) are shown in Figure 2 middle.

[0112] Example 2

[0113] CoCrMo alloy is used as substrate material and is cleaned and washed to remove impurities, and then dried before being placed on a support in the chamber of the AD device. Temperature, vacuum and other necessary parameters are set. In this case, the biocompatible protective coating layer (BPCL) is formed of silicon nitride, and titanium nitride is used as a material for forming a buffer layer. Titanium nitride powder is loaded into an independent aerosol generating unit. Then, AD deposition of the buffer layer material is started. After the deposition of the buffer layer is completed, AD deposition of silicon nitride is started. After the deposition of the biocompatible protective coating layer (BPCL) is completed, the vacuum is broken and the semi-finished product is post-processed to obtain an exemplary medical implant component.

[0114] Example 3 (comparative)

[0115] A medical implant component is provided by using magnetron sputtering of a silicon nitride layer on a CoCrMo substrate.

[0116] Example 4 (Comparative)

[0117] A medical implant component is provided by using magnetron sputtered chromium nitride as a buffer layer on a CoCrMo substrate and magnetron sputtered a silicon nitride layer on the buffer layer.

[0118] Example 5

[0119] The characteristics of the medical implant components described in Examples 1 to 4 are listed in Table 1:

[0120] Table 1

[0121]

[0122] Example 6

[0123] Study microscopic behavior and characteristics based on SEM technology. FIG. 3A to FIG. 3C SEM images of the medical implant component described in Example 1, a medical implant component with a coating layer obtained via APS, and a medical implant component with a coating layer obtained via PVD are shown. Obviously, the biocompatible protective coating layer (BPCL) is embedded in the substrate (or buffer layer, if present), specifically forming a chemical bond, and the attached area therebetween is significantly increased, and thus the attachment is strong. In contrast, conventional coated layers (such as obtained via APS or PVD) and their substrates may exhibit spaces or gaps. Porosity is present in the coated layer (see Figure 3B ), while there is no coating layer embedded in the substrate (see Figure 3C ).

[0124] Example 7

[0125] Wear tests were performed on medical implant components (knee joints) prepared based on the method described in Example 1 and conventional knee joints for comparison. Wear tests were performed and the conditions and results are summarized in Table 2 below. Specifically, under a specified normal force, the wearer test article was tested using a wearer that traveled a specified distance under a specific diameter. The wear amount was calculated based on the travel diameter and the wear area. The optical image of the knee joint (Example 1) and the SEM image of the knee joint (Example 1) and the conventional knee joint (without a coating layer or via PVD coating) are shown in 4A to 4D Obviously, the products of the present invention exhibit superior characteristics (particularly, anti-wear characteristics) to conventional products, such as significantly smaller wear amount under higher normal force and travel distance tests (see, sample A vs. sample B), higher wear resistance (see, sample A vs. sample C, similar wear amount under more severe test conditions).

[0126] Table 2

[0127]

[0128] The bottom of the screw after wear testing is also provided ( Figure 5A ) and the opposite side ( Figure 5B and Figure 5C ), which clearly shows minimal wear of the coated layer after the wear test.

[0129] The present invention clearly demonstrates superior effects over existing medical implant components. In particular, the adhesion between the biocompatible protective coating layer and the substrate is significantly enhanced. In addition, when other deposition techniques (such as magnetron sputtering) are used, the deposition rate may be limited by the nature of the technique; even with higher rates, desired features such as low porosity, low surface roughness, high adhesion, etc. cannot be provided. Without being bound by theory, higher deposition rates of materials such as magnetron sputtering may result in higher defect density, higher porosity, higher roughness, etc. of the deposited layer. In addition, when the deposition rate increases, the temperature of the substrate subjected to deposition may increase, which may have undesirable effects or influences on the deposited layer.

[0130] Those skilled in the art will appreciate that changes and modifications may be made to the teachings and disclosures of the present invention without departing from the spirit and scope of the present application. Based on the above, the present application is intended to cover any changes and modifications thereof, with the proviso that the changes or modifications or their equivalents fall within the scope defined by the attached patent claims.

Claims

1. A medical implant assembly comprising: (a) a biocompatible substrate, and (b) a biocompatible protective coating layer BPCL, which is located above or on the substrate; wherein the biocompatible substrate is made of one or more materials selected from the group consisting of: a biocompatible polymeric material, a biocompatible metal or alloy, and The biocompatible protective coating layer BPCL has a porosity of less than 1.5%.

2. The medical implant component of claim 1, wherein the biocompatible protective coating layer BPCL is formed of one or more materials selected from the group consisting of: aluminum oxide, silicon nitride, metal nitride, and any combination thereof.

3. The medical implant component according to claim 1 or 2, wherein the biocompatible protective coating layer BPCL has a thickness of 0.5 μm to 70 μm.

4. The medical implant component according to any one of claims 1 to 3, wherein the biocompatible protective coating layer BPCL has a hardness or Vickers hardness of 800 HV to 1400 HV.

5. The medical implant component according to any one of claims 1 to 4, wherein the biocompatible protective coating layer BPCL has a surface roughness of less than 0.25 μm.

6. The medical implant component of any one of claims 1 to 5, wherein the stoichiometry of the atoms of the biocompatible protective coating layer BPCL material varies by less than 20%.

7. The medical implant component according to any one of claims 1 to 6, wherein the biocompatible protective coating layer BPCL is formed of particles having a D50 in the range of 0.1 μm to 10 μm.

8. The medical implant component of any one of claims 1 to 7, wherein the biocompatible polymeric material is selected from the group consisting of polyketones, (halogenated) polyolefins and polyurethanes.

9. The medical implant component according to any one of claims 1 to 8, wherein the biocompatible polymer material is selected from the group consisting of polyetheretherketone (PEEK), polyethylene (PE), polytetrafluoroethylene (PTFE), polyvinyl chloride (PVC) and polyurethane (PU).

10. The medical implant component of claim 9, wherein the PE is low-density polyethylene (LDPE), high-density polyethylene (HDPE) or ultra-high molecular weight polyethylene (UHMWPE).

11. The medical implant component of any one of claims 1 to 10, wherein the biocompatible polymeric material has a hardness or Vickers hardness of at least 400 HV or a Shore D hardness of at least 50.

12. The medical implant component of any one of claims 1 to 7, wherein the biocompatible metal or alloy is selected from the group consisting of titanium Ti or its alloys, zirconium Zr or its alloys, tantalum Ta or its alloys, niobium Nb or its alloys, stainless steel, cobalt-chromium-molybdenum Co-Cr-Mo alloy and Ti-6Al-4V alloy.

13. The medical implant component of any one of claims 1 to 7, wherein the biocompatible ceramic is selected from the group consisting of oxides, carbides, nitrides or nitrocarbides of any one of the following elements: silicon Si, titanium Ti, tantalum Ta, tungsten W, zirconium Zr, niobium Nb, chromium Cr and aluminum Al.

14. A medical implant component as claimed in any preceding claim, further comprising a buffer layer, wherein the buffer layer is located between the biocompatible substrate and the biocompatible protective coating layer BPCL, and wherein the buffer layer is made of an oxide, nitride or carbide of any of the following elements: silicon Si, aluminum Al, zirconium Zr and boron B.

15. The medical implant component of claim 14, wherein the buffer layer has a thickness of 0.5 μm to 10 μm.

16. The medical implant component of claim 14 or 15, wherein the adhesion between the buffer layer and the substrate is at least 18 MPa.

17. The medical implant component according to any one of claims 1 to 16, which is part or the whole of an artificial joint, part or the whole of an insert associated with an artificial joint, or part or the whole of a temporary anchoring device.

18. A method for manufacturing a medical implant component according to any one of claims 1 to 17, comprising the following steps: (i) providing a biocompatible substrate in a deposition chamber; (ii) reducing the pressure in the deposition chamber to less than 0.75 Torr; and (iii) depositing a material of a biocompatible protective coating layer BPCL via aerosol deposition AD to form the biocompatible protective coating layer BPCL over or on the substrate.

19. The method of claim 18, further comprising a step (ii') after the step (ii): (ii') depositing a buffer layer material selected from the group consisting of oxides, nitrides or carbides of any one of the following elements to form a buffer layer on the substrate, and Wherein said step (iii) is step (iii'): (iii′) depositing a material of a biocompatible protective coating layer BPCL via aerosol deposition AD to form the biocompatible protective coating layer BPCL over or on the buffer layer.

20. The method of claim 19, wherein the deposition of the buffer layer is achieved via AD, physical vapor deposition (PVD), or chemical vapor deposition (CVD).

21. The method of any one of claims 18 to 20, wherein the AD is performed using a carrier gas selected from the group consisting of: N2, O2, Ar, He, clean dry air (CDA), and any combination thereof.

22. The method according to any one of claims 18 to 20, wherein the AD is performed at a flow rate of the carrier gas of 180 to 2400 l / hr.

23. The method of any one of claims 18 to 22, wherein the temperature of the substrate during the deposition is in the range of 5°C to 50°C.

24. The method of any one of claims 18 to 23, wherein the material powder has a D50 in the range of 0.5 μm to 10 μm.

25. The method of any one of claims 18 to 24, wherein the biocompatible substrate is made of one or more materials selected from the group consisting of: a biocompatible polymeric material, a biocompatible metal or alloy, and a biocompatible ceramic.

26. The method of claim 25, wherein the biocompatible polymeric material is selected from the group consisting of polyketones, (halogenated) polyolefins and polyurethanes.

27. The method of any one of claims 18 to 24, wherein the biocompatible polymeric material is selected from the group consisting of polyetheretherketone (PEEK), polyethylene (PE), polytetrafluoroethylene (PTFE), polyvinyl chloride (PVC) and polyurethane (PU).

28. The method of claim 27, wherein the PE is low density polyethylene (LDPE), high density polyethylene (HDPE) or ultra high molecular weight polyethylene (UHMWPE).

29. A medical implant component, characterized in that It comprises a biocompatible protective coating layer BPCL and optionally a buffer layer, wherein the biocompatible protective coating layer BPCL has a porosity of less than 1.5%.

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