WO2025034774A1

WO2025034774A1 - Bioactive glass-silicide coatings for osseointegratable metal implants

Info

Publication number: WO2025034774A1
Application number: PCT/US2024/041163
Authority: WO
Inventors: Steven N. Girard
Original assignee: Wisys Technology Foundation, Inc.
Priority date: 2023-08-07
Filing date: 2024-08-07
Publication date: 2025-02-13

Abstract

A method of coating bioactive glasses onto metal involves generating a silicide interfacial coating onto the metal, followed by coating with bioactive glass. Silicides are ideal interfaces between metal and glass; a robust chemical bond is formed between metal and silicide, and the glass-like layer on the silicide surface (native oxide) chemically bonds to bioactive glass. The present invention will enable bioactive glass coatings to be used as a transformative technology for osseointegrated implants.

Description

BIOACTIVE GLASS-SILICIDE COATINGS FOR OSSEOINTEGRATABLE METAL IMPLANTS

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of US provisional application 63/531,107 filed August 7, 2023 and hereby incorporated by reference.

BACKGROUND OF THE INVENTION

[0002] The present invention relates to coatings to promote osseointegration of prostheses and in particular to a method of adhering bioactive glass to the metal substrates of such prostheses.

[0003] Artificial bone implants are desirably low-cost, nontoxic, resistant to corrosion, easily machined, biocompatible (not easily rejected by the body), low density, and have excellent mechanical properties (e.g., hardness, high tensile strength, elasticity/Young’s modulus, and resistance to crack and fail). Consequently, metals, particularly titanium, steel, and their alloys, have been the implant materials of choice for decades as bone stabilizers (e.g., rods, plates, pins, screws) or replacements. State-of-the-art limb implants can extend through the skin via transcutaneous interfaces, an extension of the patient’s skeleton, improving force/vibration sensation through the implant, while evenly distributing weight.

[0004] Desirably, artificial bone implants will be osseointegrated such that the bone grows into the implant (and vice versa), creating a permanent bond. This presents a significant challenge, as most metal implants show very limited bioactivity (i.e. fusion and intergrowth with bone tissue) which necessitates novel coatings to enable effective osseointegration.

[0005] The ideal metal implant coating must be chemically bonded to the metal crystals of the implant while also binding to bone tissue so as not to fail; antibacterial; nontoxic; bioactive (promoting the regeneration of bone tissue); and able to coat complex, sometimes porous, implant geometries that are increasingly custom fabricated using additive manufacturing (e.g., 3D printing). Polymer coatings demonstrate antibacterial properties and are simple to process and apply but have found limited use for osseointegration due to their weak chemical bonding to metals (hydrophobicity), as well as low bioresorbability and potential toxicity.

[0006] Oxide/ceramics (including hydroxyapatite) have found extensive use as metal implant coatings due to their inertness, ease of synthesis, antibacterial properties, nontoxicity, and biocompatibility due to their similar composition to bone. However, ceramics have low porosities needed for bone tissue to regenerate, frequently delaminating at the implant interface due to chemical incompatibility with metal, and usually require plasma thermal spray applications that cannot coat porous and complex implant geometries.

[0007] Bioactive glasses are unique synthetic materials that are osteostimulative. The glass breaks down within the human body, resulting in the controlled release of bone-growth ions from the glass (Si, Ca, and P) which facilitate the formation of new bone cells and blood vessels, regenerating new bone. Consequently, bioactive glasses demonstrate superior bioactivity when compared to all other implant coating technologies, resulting in shorter patient recovery times, enhanced osseointegration, and a reduced likelihood of infection or failure. However, as compared to ceramics/polymers, the chemistry and degradation of bioactive glass is very difficult to control. Their bioactivity is dependent on remaining vitrified (glassy), but bioactive glasses are metastable and decompose (devitrify /crystallize) into ceramic hydroxyapatite/silica upon thermal treatment in air, ruining their bioactivity.

[0008] Bioactive glasses also do not readily bond to metal, and coating approaches such as enameling, sol-gel precipitation, and plasma spraying encourage devitrification.

SUMMARY OF THE INVENTION

[0009] The present inventor has developed a new method of adhering bioactive glasses onto metal by applying a silicide interfacial coating onto the metal. This coating has a natural oxide offering improved adhesion to bioactive glass.

[0010] In one example embodiment, the invention provides a bone prosthesis for osseointegration to bone of a patient including: a metal loadbearing substrate; a silicide layer coating the metal loadbearing substrate over a portion to be osseointegrated; and a bioactive glass coating applied over the silicide layer at a thickness promoting osseointegration with surrounding living bone.

[0011] It is thus a feature of at least one embodiment of the invention to provide improved bonding of biologically active glass to the loadbearing surfaces of metal prostheses.

[0012] The bioactive glass is desirably in a vitreous state.

[0013] It is thus a feature of at least one embodiment of the invention to preserve the bioactivity of the bioactive glass.

[0014] The metal loadbearing substrate may be a stainless steel and alloys thereof and the silicide layer may be a compound of iron and silicon; the metal loadbearing substrate may be titanium and alloys thereof and the silicide layer may be a compound of titanium and silicon; the metal loadbcaring substrate may be cobalt and alloys thereof and the silicide layer may be a compound of cobalt and silicon; the metal loadbearing substrate may be chromium and alloys thereof and the silicide layer may be a compound of chromium and silicon; the metal loadbearing substrate may be tantalum and alloys thereof and the silicide layer may be a compound of tantalum and silicon.

[0015] It is thus a feature of at least one embodiment of the invention to provide a bioactive glass surface for common metals used in prostheses.

[0016] In one example, the metal loadbearing substrate may be a rod of a leg prosthesis sized to be received within a human femur to provide loadbearing support of a human patient standing on the leg prosthesis.

[0017] It is thus a feature of at least one embodiment of the invention to provide robust osseointegration suitable for demanding prostheses applications.

[0018] These particular objects and advantages may apply to only some embodiments falling within the claims and thus do not define the scope of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Fig. 1 is a perspective view in partial cross-section of an osseointegrated bone prosthesis showing, in inset, the metal prosthesis shaft in cross-section depicting successive layers of silicide, native oxide, and bioactive glass;

[0020] Fig. 2 is a simplified elevational cross-section of a molten salt bath for forming the silicide and native oxide layers of Fig. 1;

[0021] Fig. 3 is a flowchart showing the principal steps of manufacture of the prosthesis of Fig- 1;

[0022] Fig. 4 is an elevational cross-section showing a dental implant suitable for use with the present invention; and

[0023] Fig. 5 is an elevational cross-section showing a cochlear implant receiver also suitable for use with the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT Prosthesis Example

[0024] Referring now to Fig. 1, a leg prosthesis 10 may be attached to a human limb 12 by osseointegration of a prosthesis shaft 14 into a leg hone 16 such as the femur. In this process, a closely conforming cylindrical bore is created in the distal end of the leg bone 16 and the shaft 14 is fitted tightly within that bore. As is generally understood in the art, a distal end of the shaft 14 may attach to a mechanical knee joint 18, in turn attaching a mechanical lower leg portion 20 terminating at a mechanical foot 24, the latter attached to the lower leg portion 20 by means of an ankle mechanism 26. These mechanical elements of the knee jointl8, lower leg portion 20, mechanical foot 24, and ankle mechanism 26 will generally include pivoting elements, spring biasing elements, and elastic cushioning elements as are also understood in the ail.

[0025] In one example, the shaft 14 may provide a central cylindrical substrate 30 of biocompatible metal such as titanium or stainless steel. This substrate 30 will be sized to provide suitable rigidity and support of the patient during use of the prosthesis 10. When the substrate 30 is stainless steel, it may, for example, be 316T stainless steel produced to ASTM F138 I F139 or a nickel-free stainless-steel alloy. More generally, the shaft 14 may be constructed of materials suitable for metal implants including steel (iron), titanium, chromium, cobalt, and tantalum and all of their alloys. Alloys are defined as a homogenous mixture of metals comprising a majority metal component and a smaller percentage of other metals. For example, the titanium alloy called Ti-6A1-4V is frequently used for titanium implants, comprised of approximately 90% Ti, 6% Al, and 4% V. Stainless steel is another alloy, consisting of iron and carbon, but also potentially including many other metals including Co, Mo, Ni, Ti, Ta, etc. Since all of the metals in question can generate silicides, and we can generate any silicide using this technology, any metal implant technology- including alloys- can be coated.

[0026] An outer surface of the substrate 30 will receive a surface coating 29 on portions that will be contacting the bone 16. The surface coating 29 provides a first layer of chemically bonded silicide 32. The silicide 32 reacts with environmental oxygen on its outer surface to present a layer of native oxide 34 which may then receive a final outer layer of bioactive glass 36.

[0027] As is understood in the art, silicide is a chemical compound combining silicon and an electropositive element, in this case, the metal of the substrate 30, to produce a silicide such as TiSi2 when the substrate 30 is titanium and a silicide such as FcSi when the core is a stainless steel having a ferrous component. Generally, the invention contemplates multiple possible silicide phases, for example, in the case of titanium, including TiSio, TiSi, TisSh. etc. [0028] The silicide 32 when exposed to oxygen, naturally forms a protective glass-like native oxide layer 34 on its surface rich in silica (SiO₂) providing a good surface for bioactivc glass growth and adhesion. This native oxide 34 may be in excess of 2 nm and typically less than 20 nm in thickness.

[0029] The final layer provides a bioactive glass 36. The bioactive glass 36 will be comprised of a large amount of silica (SiO2, >50 wt%) along with CaO, Na2O, and P2O5. As a glass it is amorphous (e.g., not crystalline, but rather vitrified). Generally, the bioactive glass 36 will be osteostimulative, breaking down when introduced into the human body resulting in a controlled release of bone-growth ions from the glass, such as calcium or phosphorous, which facilitate the formation of new bone cells and blood vessels effectively regenerating new bone. This novel bioactivity is unique to bioactive glass and is not observed for crystalline (devitrified) bioactive glass or any other synthetic bioceramics such as hydroxyapatite, alumina, or zirconia. Bioactive glasses are susceptible to devitrification with thermal treatment. Hence, if bioactive glass is to be used as an implant coating 29, it is preferably directly grown onto the metal substrates 30, instead of synthesized first and then post-processed via enameling or thermal spray.

[0030] Example bioactive glass 36 may be selected from but is not limited to the following compositions:

[0031] 45S5: 45 wt% SiO₂, 24.5 wt% CaO, 24.5 wt% Na₂O and 6.0 wt% P2O5.

[0032] S53P4: 53 wt% SiO₂, 23 wt% Na₂O, 20 wt% CaO and 4 wt% P2O5.

[0033] 58S: 58 wt% SiO₂, 33 wt% CaO and 9 wt% P2O5.

[0034] 70S30C: 70 wt% SiO₂, 30 wt% CaO.

[0035] 13-93: 53 wt% SiO₂, 6 wt% Na₂O, 12 wt% K₂O, 5 wt% MgO, 20 wt% CaO, 4 wt%

P₂O₅.

[0036] Bioactive glass 45S5 is commercially available under the trade name NovaMin from the GlaxoSmithKline company having headquarters in London, UK.

[0037] The layer of silicide 32 provides a good interface between the substrate 30 and bioactive glass by providing a chemical bond formed between the metal of the substrate 30 and silicide 32, and the glass-like layer on the silicide surface (native oxide) bonding to bioactive glass 36. The silicided metals allow dense bioactive glass coatings, upwards of 10 microns in thickness. The silicide 32 and bioactive glass 36 coatings remain well-adhered to the metal surface, and are significantly more facile, enabling bioactive glass coatings on complex implant geometries.

Manufacture

[0038] Referring now to Figs. 2 and 3, the process of fabricating the shaft 14 may begin by generating a coating of silicide 32 on a properly sized and shaped substrate 30 indicated by process block 40. In this process, the substrate 30 is submerged into a bath 42 of liquid salt containing solvated silica (silicon dioxide) and in the presence of a reducing agent (such as magnesium 35 or an external power/electrolysis from a power source 37). This process provides an even and robust layer of metal silicide 32 (such as TiSi2 or FeSi2). All silicon and silicide materials in air generate a glass-like oxide layer on their surface (“native oxide”), which can serve as an ideal substrate onto which bioactive glass can then be grown.

[0039] In one example, a substrate 30 of Ti and/or stainless steel may be immersed in solutions of liquid LiCkKCl eutectic salts (45:55 mol%). Silica (SiCh) glass nanoparticles may then be added along with magnesium as a reducing agent. The solvation of silica is improved by the addition (—10 wt.%) of an alkali or alkaline earth oxide, such as Li2O, Na2O, or CaO. The silica is reduced into silicon via SiO2(s) + Mg(s) Si(s) + MgO (s), and MgO can be dissolved in 2 M HC1 (Si is insoluble). The generated silicon then reacts onto the surface of the substrate 30, generating phases of silicide 32. For all silicides 32 generated, a native oxide 34 is exposed. [0040] In one embodiment, reducing electrons are provided from an external power source 37 through, for example, a titanium, tungsten or molybdenum conductor connected to the substrate 30. This conductor acts as a cathode providing reducing electrons for depositing silicide 32 on the surface of the substrate 30. Dissolved silica/silicates within the molten salt (abbreviated sin, solvated in molten salt) will then react onto the metal surface, generating a silicide. This is a two-step process, first where solvated silica is reduced to silicon; the silicon then rapidly reacts on the metal surface to generate an intermetallic silicide phase per the following reactions:

Silicon generation: [SiCh (sin) + 4e" — > Si (s) + 2O²' (sin)] x2; Silicide generation: Ti (s) + 2 Si (s) — TiSi2 (s).

[0041] The solvated oxide species then react at the sacrificial carbon anode 44 to generate carbon dioxide and complete the electrolysis via: 2O²' (sin) + C (s) — > CO2 (g) + 4e’.

In the case where the substrate 30 is steel or iron-based, the reaction will be: Silicon generation: [SiCb (sin) + 4e" — > Si (s) + 2O²' (sin)] x2; Silicide generation: Fc (s) + 2 Si (s) — > FcSi2 (s).

[0042] When a reducing agent such as magnesium is being used the equations will be as follows:

Net reduction oxidation reaction: SiC (sin) + 2Mg (s) — >■ Si (s) + 2MgO (s). Oxidation half-reaction: 2Mg (s) — 2Mg²⁺ (sin) + 4e' Reduction half-reaction: SiO2 (sin) + 4e" — Si (s) + 2O²" (sin) Silicide generation: Ti (s) + 2 Si (s) — TiSi2 (s).

[0043] Residual MgO can be easily dissolved in acid afterwards; the resulting silicide is inert to most acids (as with Si) after a native oxide layer is generated on the surface of the silicide.

[0044] Referring again to Fig. 3, at process block 50, a natural oxide coating 34 is formed through reactions with environmental oxygen present in air. Next at process block 52, the bioactive glass 36 is applied to the natural oxide coating 34. In one embodiment, this is performed using a sol-gel method mixing appropriate amounts of tretraethylorthosilicate, calcium nitrate, sodium nitrate, and triethyl phosphate (assuming 45 wt% SiCh, 24.5 wt% CaO, 24.5 wt% NazO, and 6.0 wt% P2O5 to generate the bioactive glass 45S5, for example), catalyzed by 1 M nitric acid. The resulting coating will be stabilized by hydrothermal reaction at 70 °C for 24 hours, dried at 120 °C for 24 hours, and annealed at 700 °C for 3 hours to generate a bioactive glass-wire powder mixture. In another embodiment, melt-quenched bioactive glass is applied to the natural oxide coating 34. The melt-quenched bioactive glasses are generated by mixing appropriate ratios of inorganic metal oxides, such as those in [0032] -[0036], within platinum crucibles at temperatures 1300-1600 °C, rapidly cooling in cold water, then grinding the resulting glass into a fine powder. The melt-quenched bioactive glass is applied to the natural oxide coating 34 by annealing bioactive glass powders at 700 °C for 3 hours.

[0045] The result is a dense amorphous coating of bioactive glass 36, upwards of 10 microns in thickness. In various embodiments the bioactive glass 36 may be greater than 500 nm, greater than 10 pm, or greater than 50 pm in thickness.

[0046] Aside from the native oxide 34, which enables the adherence of the bioactive glass 36 to the substrate 30, the layer of silicide 32 provides comparable values of coefficient of thermal expansion (CTE) as the underlying metal (8-10xl0’⁶ K’¹). As a result, the silicide 32 and subsequently bioactive glass 36 remain well-adhered to the metal surface and do not crack or delaminate.

[0047] While the present invention is described with respect to a leg prosthesis, it will be appreciated that it has value in other prostheses and medical devices where bonding to bone is important, including dental implants 60, for example, shown in Fig 4, where the coating 29 may be applied a post used to anchor the dental implant 60 to bone of the jaw 61, or receivers 62 for cochlear implants also having the coating 29 that may be implanted in the bone of the skull 64 as shown in Fig. 5.

[0048] The term "vitreous" refers to an amorphous or non-crystalline structure of at least 50% of the material available for bonding to bone.

[0049] Certain terminology is used herein for purposes of reference only, and thus is not intended to be limiting. For example, terms such as "upper", "lower", "above", and "below" refer to directions in the drawings to which reference is made. Terms such as "front", "back", "rear", "bottom" and "side", describe the orientation of portions of the component within a consistent but arbitrary frame of reference which is made clear by reference to the text and the associated drawings describing the component under discussion. Such terminology may include the words specifically mentioned above, derivatives thereof, and words of similar import. Similarly, the terms "first", "second" and other such numerical terms referring to structures do not imply a sequence or order unless clearly indicated by the context.

[0050] When introducing elements or features of the present disclosure and the exemplary embodiments, the articles "a", "an", "the" and "said" are intended to mean that there are one or more of such elements or features. The terms "comprising", "including" and "having" are intended to be inclusive and mean that there may be additional elements or features other than those specifically noted. It is further to be understood that the method steps, processes, and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated, unless specifically identified as an order of performance. It is also to be understood that additional or alternative steps may be employed.

[0051] It is specifically intended that the present invention not be limited to the embodiments and illustrations contained herein and the claims should be understood to include modified forms of those embodiments including portions of the embodiments and combinations of elements of different embodiments as come within the scope of the following claims. All of the publications described herein, including patents and non-patent publications, are hereby incorporated herein by reference in their entireties.

[0052] To aid the Patent Office and any readers of any patent issued on this application in interpreting the claims appended hereto, applicants wish to note that they do not intend any of the appended claims or claim elements to invoke 35 U.S.C. 112(f) unless the words “means for” or “step for” are explicitly used in the particular claim.

Claims

CLAIMS What I claim is:

1. A bone prosthesis for osseointegration to the bone of a patient comprising: a metal loadbearing substrate; a silicide layer coating the metal loadbearing substrate over a portion to be osseointegrated; and a bioactive glass coating applied over the silicide layer at a thickness promoting osseointegration with surrounding living bone.

2. The bone prosthesis of claim 1 wherein the bioactive glass is in a vitreous state.

3. The bone prosthesis of claim 1 wherein the metal loadbearing substrate is stainless steel, and the silicide layer is FeSi2.

4. The bone prosthesis of claim 1 wherein the metal loadbearing substrate is titanium, and the silicide layer is TiSi2.

5. The bone prosthesis of claim 1 wherein the metal loadbearing substrate is a rod of a leg prosthesis sized to be received within a human femur to provide loadbearing support of a human patient standing on the leg prosthesis.

6. The bone prosthesis of claim 1 wherein the bioactive glass layer is in excess of 500 nm.

7. The bone prosthesis of claim 1 wherein the bioactive glass is greater than 50% by weights of silicon dioxide and includes calcium oxide, sodium oxide, and phosphorus pentoxide.

8. The bone prosthesis of claim 1 wherein the metal loadbearing substrate is selected from the group consisting of a cochlear implant stud and a dental implant.

9. A method of manufacture of a bone prosthesis having a metal loadbearing substrate; a silicide layer coating the metal loadbearing substrate over a portion to be osseointegrated; and a bioactive glass coating applied over the silicide layer at a thickness promoting osteointegration with surrounding living bone, the method comprising:

(a) placing the metal loadbearing substrate in a bath of molten liquid salt including silicon to provide an outer silicide coating over the metal loadbearing substrate and a native oxide layer exposed on the outer surface of the silicide coating; and

(b) depositing a bioactive glass material on the native oxide layer to chemically bind therewith.

10. The method of claim 9 wherein the step of depositing a bioactive glass material maintains a vitreous state of the bioactive glass material.

11. The method of claim 9 wherein the step of growing the bioactive glass material uses a sol-gel process.

12. The method of claim 9 wherein an electrical power supply is connected to the metal loadbearing substrate providing reducing electrons to the metal part during growth of the silicide coating.

{stainless steel example}

13. The method of claim 9 wherein the metal loadbearing substrate is stainless steel, and the silicide layer is a compound of iron and silicon.

{titanium example}

14. The method of claim 9 wherein the metal loadbearing substrate is titanium, and the silicide layer is a compound of titanium and silicon.

{leg prostheses}

15. The method of claim 9 wherein the metal loadbearing substrate is a rod of a leg prosthesis sized to be received within a human femur to provide loadbearing support of a human patient standing on the leg prosthesis. {meaningful bioactive glass layer}

16. The method of claim 9 wherein the bioactivc glass layer is in excess of 500 nm.

{broad definition of bioactive glass}

17. The method of claim 9 wherein the bioactive glass is greater than 50% by weight of silicon dioxide and includes calcium oxide, sodium oxide, and phosphorus pentoxide.

{ other example uses }

18. The method of claim 9 wherein metal loadbearing substrate is selected from the group consisting of a cochlear implant stud and a dental implant.

19. The method of claim 9 further wherein step (a) includes a solvation of silica with an alkali or alkaline earth oxide.

20. The method of claim 19 wherein the alkali or alkaline earth oxide is selected from the group consisting of: LhO. NaiO, or CaO.