THREE DIMENSIONALLY PRINTED AND NANOCOATED MEDICAL IMPLANTS

Abstract

Fabrication methods and structures for three dimensional medical implants are provided.

Claims

1. A method for forming a medical implant, the method comprising: forming a three dimensional structure using three dimensional (3D) printing, said three dimensional structure having x, y, and z structural geometry in a three dimensional x, y, and z Cartesian coordinate system; coating said three dimensional structure with an anti-infection material having a thickness in the range of 0.5 nanometers to 1.0 micrometers.

2. The method of claim 1, wherein said coating said three dimensional structure with an anti-infection material is performed using atomic layer deposition.

3. The method of claim 2, wherein said coating said three dimensional structure with an anti-infection material is performed using plasma enhanced atomic layer deposition.

4. The method of claim 1, wherein said coating said three dimensional structure with an anti-infection material is performed using chemical vapor deposition.

5. The method of claim 4, wherein said coating said three dimensional structure with an anti-infection material is performed using plasma enhanced chemical vapor deposition.

6. The method of claim 1, wherein said coating is a metal.

7. The method of claim 7, wherein said metal is silver.

8. The method of claim 1, wherein said coating is an antibiotic.

9. The method of claim 8, wherein said antibiotic is gentamicin.

10. The method of claim 3, wherein said coating is a metal.

11. The method of claim 10, wherein said metal is silver.

12. The method of claim 5, wherein said coating is an antibiotic.

13. The method of claim 12, wherein said antibiotic is gentamicin.

14. The method of claim 1, wherein said three dimensional structure is made of titanium.

15. A medical implant, comprising: a three dimensional structural component having x, y, and z structural geometry in a three dimensional x, y, and z Cartesian coordinate system, said three dimensional structural component made of at least a structural material and a nanocoating; a nanocoating of anti-infection material having a thickness in the range of 0.5 nanometers to 1.0 micrometers and coating said three dimensional structural material.

16. The medical implant of claim 15, wherein said coating is a metal.

17. The medical implant of claim 16, wherein said metal is silver.

18. The medical implant of claim 17, wherein said coating is an antibiotic.

19. The medical implant of claim 18, wherein said antibiotic is gentamicin.

20. The medical implant of claim 15, wherein said three dimensional structural component is made of titanium.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The features, natures, and advantages of the disclosed subject matter may become more apparent from the detailed description set forth below when taken in conjunction with the drawings in which like reference numerals indicate like features and wherein:

[0011] FIG. 1 is a drawing showing examples medical spine implants;

[0012] FIG. 2 is a drawing showing examples of medical hip and face implants; and

[0013] FIG. 3 is a drawing showing disclosed subject matter solutions as compared to state of the art solutions.

DETAILED DESCRIPTION

[0014] The following description is not to be taken in a limiting sense, but is made for the purpose of describing the general principles of the present disclosure. The scope of the present disclosure should be determined with reference to the claims. Exemplary embodiments of the present disclosure are illustrated in the drawings, like numbers being used to refer to like and corresponding parts of the various drawings. The dimensions of drawings provided are not shown to scale.

[0015] As used in the description of the embodiments and the appended claims, the singular forms a, an and the are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will also be understood that the term and/or as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. It will be further understood that the terms comprises and/or comprising, when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.

[0016] As used herein, the term if may be construed to mean when or upon or in response to determining or in accordance with a determination or in response to detecting, that a stated condition precedent is true, depending on the context. Similarly, the phrase if it is determined [that a stated condition precedent is true] or if [a stated condition precedent is true] or when [a stated condition precedent is true] may be construed to mean upon determining or in response to determining or in accordance with a determination or upon detecting or in response to detecting that the stated condition precedent is true, depending on the context.

[0017] As used herein, the term infection is used to refer to the presence of any undesirable pathogen, most commonly bacteria, but may also include prions, viruses, protozoa, fungi, nematodes, as well as abnormal human cells. Colonization is used interchangeably with infection.

[0018] As used herein, the term PEEK is used to refer both to polyether ether ketone, a colourless organic thermoplastic polymer as well as the larger polyaryletherketone (PAEK) family such as PEKK (polyetherketoneketone).

[0019] As used herein, the term anti-infection coating is used to refer a coating, which comprises a single material or composite of materials that provides active and/or passive effects that ultimately decrease the risk of infection. An active effect would be a bactericidal or bacteriostatic effect in which bacteria is killed or the ability for the bacteria to reproduce is impaired. Another active effect would be enhancement of the host immune system to defend against bacteria. A passive effect would be change in the surface properties that affects the the ability for a pathogen to adhere and colonize the implant.

[0020] It is understood that a composite of materials can consist of a homogeneous or heterogenous mix of multiple materials. The materials may be doped heterogeneously at different proportions (i.e. 10% silver) exposed to the surface. The coatings may be applied serially in which a copper-based coating is applied to an implant and then a graphene-based coating is applied to the copper. Examples of anti-infection coatings include drugs, metals, alloys, oxides, nitrides, vitamins, ceramics, plastics, and allotropes of elements such as Carbon (e.g. graphene).

[0021] As used herein, the term three-dimensional implants and reference to additive and subtractive manufacturing is used to discuss differences in capabilities for lattice and surface finish. It is understood that non-additive manufacturing methods that generate lattice or porous structures typically associated with additively manufactured methods, hybrid methods that use a combination of additive or subtractive methods to generate a final implant design that has a lattice or specific surface finish can also be called a three-dimensional second generation implant.

[0022] The present application provides a solution for next generation medical implantsfor example spine, interbody fusion, neck, knee, ankle, face, and hip implantswhich overcome the shortcomings of existing medical implants, namely the present application provides complex three dimensional structures with improved infection protection. The medical implant solutions provided retain the structural, lattice/porosity benefits of second-generation medical implants, particularly metal based 3D printed titanium implants, while providing exceptional anti-infection properties. This has the potential to significantly improve the quality of life for patients and reduce the mounting costs related to revision surgeries.

[0023] One path to reduce infections is by coating medical implants with special materials such as metals, metal coatings have been found to be highly efficacious, or antibiotics. Metal coatings such as silver, copper, and selenium have shown promising results in terms of reduction in infections through decreased bacterial adhesion, enzyme activity inhibition, and production of reactive oxygen species. However, previously known medical implant structures with metal coatings, such as those coated using galvanic deposition, may suffer from both imprecise coatings and thicker coatings such as those having a thickness greater than several micrometers. Additionally, line of sight deposition methods may not optimally cover complex implant structures that by nature have significant geometrical self-shadowing. Thus, using conventional deposition techniques, this shadowing may result in incomplete, non-uniform coatings.

[0024] Relating to antibiotic coatings, in limited studies simple techniques such as electrophoresis have been used to coat gentamicin. However, one challenge is that these antibiotic coating processes tend to be thicker, non-selective (i.e., cover the entire implant), and non-conformal. Further, the thicknesses can vary across the complex implant structures due to sharp edges and varying surface areas causing a non-uniform electric field during electrophoresis. For example, in one extreme, on certain parts of the implant the antibiotic may be absent resulting in a fertile ground for infection, while on other parts of the implant the antibiotics may be too thick thus reducing the benefits of the implant's structural intricacies. At very large thicknesses the aforementioned underlying implant properties (such as latticing and porosity induced functions) start to get compromised resulting in possible reduction in osseointegration. Additionally, the range of antibiotics that may be deposited using conventional techniques may be limited.

[0025] In another embodiment, ascorbic acid (vitamin C) may be used to enhance the bone formation. This provides an indirect anti-infection activity by accelerating the rate of bone formation and associated vascularization which can enhance the host's ability to defend against infection and decrease the available surface area for pathogenic colonization.

[0026] In another embodiment, graphene, an allotrope of carbon is used to alter the ability for pathogens such as bacteria to adhere to an implant and to create a hostile environment for bacterial growth and expansion. Graphene cannot easily be coated directly onto Ti6Al4V, one common alloy used in medical implants. In such an embodiment, a Ti6Al4V or PEEK or PEKK implant would be coated initially with a copper-based layer followed by graphene.

[0027] In another embodiment, metals or alloys such as Copper or Ti6Al4V can be coated for anti-microbial activity. Copper has inherent antimicrobial activity while Ti6Al4V can be used to coat stainless steel implants as Ti6Al4V has decreased bacterial adhesion.

[0028] In another embodiment, ceramics such as zirconia oxide or alumnia oxide may be used to coat an implant to decrease the surface roughness, thereby decreasing the available surface area for pathogenic colonization and infection. This is particularly useful for areas of an implant that may be in contact with soft tissue and do not require surface roughness.

[0029] In another embodiment, oxides and nitrides can be can used as an anti-infection coating. Titanium oxide, Titanium nitride, and Silicon nitride are examples of materials that provide anti-infection through decreased surface adherence of bacteria and increase the rate of bone healing (thereby enhancing host defenses).

[0030] The large coating thickness ranges used in existing medical implants, for example coating thicknesses in the range of several micrometers, starts to compromise the aforementioned underlying implant properties of both the medical implant structural material, materials such as titanium and extra low interstitial titanium alloy Ti6Al4V, as well as the those stemming from the highly beneficial lattice structures. Hence, both osseointegration and the ability to negate age-related implant loosening is compromised. In conclusion, current second-generation, state-of-the-art, implants do not effectively prevent infection while maintaining effective osseointegration.

[0031] The present application provides medical implants having nano-coatings of materials, such as metals and antibiotics, using precise, low temperature, conformal deposition techniques such as but not limited to atomic layer deposition (ALD), chemical vapor deposition (CVD), ion-based deposition (example: physical vapor deposition), electrochemical deposition (example: electro and electroless plating) processes, and spray-based deposition on the medical implants. These processes are capable of depositing material thicknesses from a few angstroms to nanometer levels and may in some cases exercise angstrom level control of the film thickness. Further, plasma enhanced atomic layer deposition (PEALD) as well as plasma enhanced chemical vapor deposition (PECVD) may be used. Plasma enhanced atomic layer deposition (PEALD) and plasma enhanced chemical vapor deposition (PECVD) have the advantage of further lowering deposition temperature closer to room temperature as compared to their thermal counterparts while maintaining conformal deposition. This is because ion bombardment from plasma aids in providing the necessary activation energy for deposition, reducing the reliance on higher temperatures. Advantageously, lower temperature processes are especially useful for coatings, particularly antibiotics, whose properties are sensitive or may degrade at higher temperatures.

[0032] The very thin coatings provided herein, having a material thicknesses from a few angstroms to nanometer levels, are thin enough not to compromise the underlying exceptional intricate structural medical implant properties while being thick enough to only modify implant surfaces to provide exceptional anti-infection efficacy.

[0033] The coatings provided to coat implant surfaces have anti-infection properties. These anti-infection metal materials include silver, copper, and selenium, and these anti-infection antibiotics include gentamicin, tobramycin, ciprofloxacin, ampicillin, vancomycin, and rifampin. In a specific embodiment, silver between 1 nm to 50 um may be deposited on spine implants such as cages and screws using chemical vapor deposition at temperatures ranging from 50 C to 1000 C. In another embodiment, gentamicin or tobramycin between 0.5 nm to 1 um may be deposited on spine implants such as cages and screws using atomic layer deposition and plasma enhanced atomic layer deposition at temperatures ranging from 25 C to 100 C. In another embodiment, Ag between 0.5 nm to 500 nm may be deposited on neck, kneed, ankle, face, and hip implants using atomic layer deposition and plasma enhanced atomic layer deposition at temperatures ranging from 25 C to 400 C. These medical implant solutions provide improved anti-infection/antibiotics properties, effective osseointegration, and reduced stress shielding using nanocoating and metal 3D printing.

[0034] Challenges relating to coating very thin coatings, for example coating thicknesses less than several micrometers, on complex medical implant structures include that these structures tend to internally shade themselves. In other words, if the deposition technique is only line of sight, geometrical shading will result in uneven coating thicknesses. Hence, some parts of the implant will get the coating, while other parts may get extremely thin or no coating at all.

[0035] The solutions provided herein, using processes such as atomic layer deposition and chemical vapor deposition which have the advantage of having low surface sticking probability (sticking coefficient) of the gas phase deposited atoms (defined as the probability of a deposited atom sticking on the surface for a given impingement), overcome these geometrical shading challenges. Thus, for low sticking probability methods, the atoms coming on to the substrate tend to bounce around and get in places which otherwise would have been geometrically shielded. This is conceptually shown in FIG. 3. Lower sticking probability methods may result in coverage all around the complex medical implants including in areas which would normally be geometrically shielded from line of sight deposition techniques. The sticking coefficient may be further lowered by modifying the deposition temperature and pressure and by using alternate precursors. Thus, the proposed atomic layer deposition and chemical vapor deposition techniques have the advantage of providing uniform, consistent, and conformal coatings even on complex geometries such as latticed and porous medical implants.

[0036] Yet another challenge to coating medical implants stems from their complex three-dimensional geometries and the associated z-heights. Most existing precision deposition processes are conducive for planar semiconductor wafers. A solution provided herein is modifying nanocoating reactors to ensure that the reactors provide the same efficacy and thin film coating advantages on the three-dimensional geometries of medical implants as they do on the conventional wafers. In a specific embodiment, the plasma source is added on the atomic layer deposition reactor to create a plasma enhanced atomic layer deposition (PEALD) designed such that there is enough clearance in the z-direction to accommodate a majority of the medical implant parts.

[0037] The foregoing description of the exemplary embodiments is provided to enable any person skilled in the art to make or use the claimed subject matter. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without the use of the innovative faculty. Thus, the claimed subject matter is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.