Composition of a biocompatible and biodegradable metal alloy for medical implants

Abstract

A biodegradable, biocompatible metal alloy composition suitable for orthopedic implants, consisting of magnesium as the main component (at least 50 wt%) and at least one alloying element selected from calcium, zinc, manganese and strontium, wherein the alloy exhibits a controlled degradation rate and sufficient mechanical strength under physiological conditions to support bone healing.

Description

INVENTION AREA

[0001] The present invention relates to biodegradable, biocompatible metal alloy compositions suitable for temporary orthopedic implants. In particular, the invention relates to (i) magnesium alloys containing magnesium as a major component with at least one alloying element selected from calcium, zinc, manganese, and strontium, (ii) zinc-based alloys containing zinc as a major component with at least one alloying element selected from magnesium, calcium, and strontium, and (iii) iron-based alloys containing iron as a major component with at least one alloying element selected from manganese, zinc, and magnesium.The compositions are configured to provide sufficient mechanical support for bone healing and are subject to controlled biodegradability under physiological conditions, thereby reducing or eliminating the need for secondary implant removal surgery. BACKGROUND OF THE INVENTION

[0002] The subject matter discussed in the "Background" section should not be considered prior art solely because it is mentioned in that section. Likewise, a problem mentioned in the "Background" section or related to the subject matter of the "Background" section should not be considered prior art. The subject matter in the "Background" section merely presents various approaches, which could themselves also be inventions.

[0003] Orthopedic trauma, degenerative bone diseases, and corrective surgeries often require temporary or semi-permanent mechanical stabilization of bone segments to allow for proper healing and restoration of function. In routine clinical practice, internal fixation devices—such as bone plates, screws, pins, intramedullary nails, staples, wires, and bone anchors—are used to hold fractured or osteotomized bone fragments in the desired anatomical alignment. These devices are expected to withstand complex physiological loads (compression, tension, torsion, bending, and cyclic fatigue) while the bone undergoes biological repair processes such as callus formation, remodeling, and revascularization.In many cases, fixation devices are only required for a limited healing period; once the bone has regained sufficient strength and stability, the continued presence of the device offers only limited benefit and can lead to long-term complications.

[0004] Conventional orthopedic implants are typically made of corrosion-resistant, non-degradable metals such as titanium alloys, stainless steels, and cobalt-chromium alloys. These materials offer high strength, good fatigue resistance, and a long lifespan. However, because they are designed to remain stable in vivo, they often persist in the body even after complete bone healing. The persistent presence of such implants can cause several clinical and biomechanical problems. For example, long-term implants can lead to stress shielding, in which the implant bears a significant portion of the load and reduces mechanical stimulation of the bone, potentially slowing remodeling and causing localized bone resorption.Furthermore, remaining implants can contribute to chronic discomfort, palpability of the implant under the skin (especially in thin patients), and irritation or damage to surrounding soft tissues such as tendons and ligaments. Metal implants can also interfere with medical imaging, including CT and MRI scans, due to artifacts, and complicate future surgeries in the same area.

[0005] Importantly, many patients ultimately require a second surgical procedure to remove the implant. Such revision or removal surgeries carry additional risks, including infection, bleeding, nerve injury, anesthesia-related complications, pain, delayed return to activity, and increased costs. Implant removal can be particularly problematic in pediatric patients, where growth considerations often necessitate removal, as well as in elderly or medically compromised patients, where additional surgery increases morbidity. Even when implant removal is not strictly necessary, the possibility of late infection, loosening, or implant-related discomfort can create a clinical incentive to avoid long-term implant retention whenever possible.

[0006] To address these challenges, biodegradable polymeric fixation devices have been investigated. Polymers such as PLA, PGA, PLGA, and PCL have been used in certain low-stress applications because they can degrade in vivo over time. However, polymer implants often have limitations that restrict their wider use in load-bearing orthopedic fixation. Their mechanical strength and stiffness are generally lower than those of metal implants, and they may not provide sufficient stability for fractures subjected to significant loads. Furthermore, polymer degradation can generate acidic byproducts that, in some cases, can lead to local inflammation, sterile sinus formation, or other undesirable tissue reactions.The degradation behavior of polymers can also depend on the geometry of the device, the crystallinity, and the patient-specific biological conditions, which can lead to variations in the loss of mechanical integrity.

[0007] These limitations have led to considerable interest in biodegradable metal implants, which aim to combine the mechanical advantages of metals with the clinical benefit of gradual resorption. Biodegradable metals are designed to initially provide strong fixation and then gradually corrode in physiological environments, so that as the bone regenerates, the implant progressively loses mass and mechanical significance, eventually leaving minimal or no residual foreign material.However, the development of biodegradable metal alloys for orthopedic applications is technically challenging, as the performance of the implant depends on a delicate balance between (i) the biocompatibility of the alloy and its corrosion products, (ii) a controlled degradation rate that matches the bone healing timeline, and (iii) mechanical properties (strength, ductility, fatigue resistance) that are sufficient during the critical healing phase.

[0008] Among the potentially biodegradable metals, magnesium, zinc, and iron have received particular attention because they are either essential or compatible elements in the body and can be engineered to degrade. However, each of these base metals has distinct drawbacks when used without careful alloy design: Magnesium-based systems: Magnesium is attractive due to its low density, its modulus of elasticity, which is closer to that of bone than conventional metals (potentially reducing stress shielding), and its favorable biocompatibility when properly controlled. However, pure magnesium and many simple magnesium alloys can corrode too rapidly in chloride-containing body fluids. Rapid corrosion can lead to premature loss of mechanical integrity, local alkalization, and the formation of hydrogen gas bubbles, which, if excessive, can impair tissue healing. Therefore, magnesium implants typically require alloying and microstructural refinement to slow and stabilize corrosion, promote more uniform degradation, and maintain strength during healing.

[0009] Zinc-based systems: Compared to magnesium, zinc generally exhibits a more moderate corrosion rate in vivo, making it promising for applications requiring slower, more predictable degradation. Zinc is also an essential trace element with well-known biological functions. However, pure zinc has comparatively lower strength and may exhibit limited mechanical performance in certain fixation applications. Therefore, biodegradable zinc-based implants often require reinforcement through alloying (e.g., with magnesium, calcium, and / or strontium) and microstructure control (e.g., formation of reinforcing intermetallic phases), while simultaneously ensuring controlled degradation and minimizing toxic heavy metal contamination.

[0010] Iron-based systems: Iron has high strength and is frequently used in biomedical alloys. However, pure iron corrodes too slowly under many physiological conditions, leading to a prolonged implant lifetime. Furthermore, corrosion products can accumulate, which, if not adequately resorbed, can cause local tissue reactions. To make iron suitable as a biodegradable implant, it is generally necessary to accelerate corrosion through alloying strategies, microstructuring techniques, and galvanic coupling concepts. At the same time, conventional alloying elements used in stainless steels (such as chromium, nickel, and molybdenum) are undesirable in a biodegradable iron implant because they promote passivation and long-term corrosion resistance, which is counterproductive to the goal of controlled biodegradability.

[0011] Another challenge with all biodegradable metals is that their degradation behavior is strongly influenced by their microstructure—including grain size, second-phase precipitates, intermetallic particles, and phase distribution. Microstructural features can create microgalvanic pairs that either accelerate localized attack (leading to pitting and premature failure) or, if carefully engineered, promote uniform corrosion and a steady reduction in mechanical properties. Therefore, simply selecting a base metal is insufficient; the alloy must be designed with specific alloying elements, impurity control, and microstructural targets to ensure reliable in vivo implantation.

[0012] Accordingly, there remains a need for biodegradable and biocompatible metallic alloy compositions suitable for orthopedic implants that offer: (a) sufficient initial mechanical strength and ductility, (b) a degradation rate matched to the bone healing time, (c) controlled corrosion behavior that is preferably more uniform than aggressively localized, and (d) a reduced risk of toxicity by limiting undesirable elements and impurities. The present invention meets these requirements by providing specific magnesium-, zinc-, and iron-based alloy compositions, as well as by limiting impurities and microstructural features to achieve controlled biodegradation and a clinically useful temporary orthopedic support.

[0013] The information disclosed above in this "Background" section is provided solely for a better understanding of the background of the invention and may therefore contain information that is not part of the prior art for a person skilled in the art in this field in this country. SUMMARY

[0014] The invention provides biodegradable, biocompatible metal alloy compositions for orthopedic implants in three main embodiments.

[0015] In a first embodiment, the alloy is magnesium-based and comprises magnesium as the main component (at least 50 wt.%) and at least one alloying element selected from calcium, zinc, manganese, and strontium. In preferred embodiments, magnesium comprises at least 85 wt.% of the alloy. In a preferred composition, the alloy contains 1–5 wt.% zinc and 0.1–2 wt.% calcium, the remainder consisting of magnesium and unavoidable impurities. The microstructure may include an α-magnesium matrix with intermetallic precipitates, including a Ca₂Mg₆Zn₃ phase dispersed in the matrix. Optionally, 0.1 to 1 wt.% manganese and / or 0.1 to 1 wt.% strontium may be added. The alloy is further controlled to limit impurities of aluminum, nickel, and rare earth elements (for example, not more than a total of 0.05 wt.% aluminum, nickel, or any rare earth element).In preferred embodiments, the average grain size is no more than 20 µm in order to improve strength and corrosion uniformity.

[0016] In a second embodiment, the alloy is zinc-based and comprises zinc as the main component (at least 50 wt.%) and at least one alloying element selected from magnesium, calcium, and strontium. In preferred embodiments, zinc comprises at least 85 wt.% of the alloy. In a preferred composition, the alloy contains 1–10 wt.% magnesium and 0.1–1 wt.% calcium, the remainder consisting of zinc and unavoidable impurities; strontium may be present in an amount of 0.1–1 wt.%. Toxic heavy metal impurities such as lead, cadmium, and arsenic are kept below 0.01 wt.%. The microstructure may include a primary zinc-rich matrix phase and secondary intermetallic precipitates, including Mg₂Zn. 11include substances dispersed within it to increase strength and support controlled degradation.

[0017] In a third embodiment, the alloy is iron-based and comprises iron as the main component (at least 50 wt.%) and at least one alloying element selected from manganese, zinc, and magnesium, wherein the alloy is configured to corrode gradually in vivo while simultaneously providing bone-like mechanical support during healing. In preferred embodiments, iron comprises at least 70 wt.%. In a preferred composition, manganese is present in an amount of 20 to 35 wt.%, the remainder consisting of iron and unavoidable impurities, and the microstructure is predominantly a single-phase austenitic structure to promote ductility and more uniform corrosion. Further embodiments include 1 to 10 wt.% zinc and / or 1 to 10 wt.% magnesium to form galvanic pairs and accelerate biodegradation. Optionally, 0.1 to 1 wt.It may contain -% silver, platinum, or palladium to increase the corrosion rate. The iron alloy is essentially free of nickel, chromium, and molybdenum to avoid persistent passive layers and improve biocompatibility. DETAILED DESCRIPTION

[0018] For the purposes of this specification, the following applies: “Biodegradable” refers to the alloy’s ability to corrode or dissolve in vivo over time, so that the mass and / or structural presence of the implant decreases during the healing process.

[0019] “Biocompatible” refers to the property of the alloy and its degradation products to be compatible with physiological tissues without unacceptable toxicity and, in preferred embodiments, to meet the relevant biological evaluation criteria (e.g. cytotoxicity and hemocompatibility screening).

[0020] "Controlled degradation rate" refers to corrosion / degradation behavior that is neither excessively rapid (leading to premature loss of mechanical integrity) nor excessively slow (leading to long-term persistence). Controlled degradation can be assessed in simulated body fluid (SBF), phosphate-buffered saline (PBS), Hank's solution, or equivalent physiological media at approximately 37 °C and / or in vivo using mass loss, hydrogen evolution (for magnesium), electrochemical tests, or immersion corrosion rate measurements.

[0021] “Unavoidable impurities” refer to trace impurities originating from raw materials and processing, typically in low concentrations, and which do not significantly alter the intended properties.

[0022] “Essentially free” refers to the absence of intentionally added elements and only trace residues, preferably below the impurity limits specified in the claims.

[0023] The alloy compositions of the invention are suitable for the manufacture of temporary orthopedic implants such as bone screws, plates, pins, intramedullary nails, staples, fixation wires, and porous frameworks. The alloys can be produced using known metallurgical processes such as melting and casting, powder metallurgy, extrusion, rolling, forging, and / or additive manufacturing, followed by optional thermomechanical processing to refine the grain size and adjust the precipitate distribution, provided that the final composition remains within the claimed ranges.

[0024] In one embodiment, the invention provides a biodegradable, biocompatible magnesium-based alloy composition for orthopedic implants, in which magnesium constitutes at least 50 wt.% of the main component and at least one alloying element is selected from calcium, zinc, manganese, and strontium. Under physiological conditions, the alloy exhibits a controlled degradation rate and sufficient mechanical strength to support bone healing.

[0025] In preferred embodiments, magnesium comprises at least 85 wt.% of the alloy. A preferred composition comprises 1-5 wt.% zinc and 0.1-2 wt.% calcium, the remainder being magnesium and unavoidable impurities. In such compositions, the microstructure preferably comprises an α-magnesium matrix with intermetallic precipitates, including a Ca₂Mg₆Zn₃ phase dispersed within the matrix. The precipitate distribution and volume fraction can be adjusted by controlling the solidification rate and subsequent thermomechanical processing to improve strength while promoting more uniform corrosion behavior.

[0026] In further embodiments, 0.1–1 wt% manganese is added to support grain refinement and / or improve corrosion behavior by controlling impurity effects and / or forming stable dispersoids. Other embodiments include 0.1–1 wt% strontium alone or in combination with the aforementioned alloying elements to modify the microstructure and support a biocompatible osteogenic response while controlling degradation kinetics.

[0027] To improve safety and corrosion resistance, the alloy preferably contains no more than 0.05 wt% aluminum, nickel, or a rare earth element as an impurity. Such a limitation reduces the risk of undesirable biological reactions and avoids microgalvanic effects caused by more noble impurities.

[0028] In preferred embodiments, the alloy is processed to an average grain size of no more than 20 µm to increase the yield strength (for example, by grain boundary strengthening) and to improve corrosion uniformity by reducing localized galvanic microcells. Grain size control can be achieved by thermomechanical processing such as extrusion, rolling, co-channel angular pressing, or controlled heat treatment without deviating from the claimed composition.

[0029] In a second embodiment, the invention provides a biodegradable, biocompatible zinc-based alloy composition suitable for orthopedic implants, comprising zinc as the main component (at least 50 wt.%) and at least one alloying element selected from magnesium, calcium, and strontium. The alloy exhibits a controlled rate of biodegradation and mechanical properties sufficient for temporary bone fixation.

[0030] In preferred embodiments, zinc comprises at least 85 wt.% of the alloy. A preferred composition includes 1-10 wt.% magnesium and 0.1-1 wt.% calcium, the remainder consisting of zinc and unavoidable impurities. In further embodiments, the alloy comprises 0.1-1 wt.% strontium to modify degradation and improve the biomechanical response.

[0031] To ensure safety, the alloy contains less than 0.01 wt% of toxic heavy metal impurities, selected from lead, cadmium, or arsenic. In preferred embodiments, the alloy is produced using high-purity starting materials and controlled melting and refining processes to keep the heavy metal impurities below the specified limit.

[0032] The microstructure of preferred zinc-based embodiments comprises a primary zinc-rich matrix phase and a secondary intermetallic phase containing dispersed Mg2Zn. 11-contains excretions. The intermetallic excretions provide reinforcement and can also influence biodegradation through microstructure control, thus enabling a gradual and predictable reduction of implant mass while maintaining sufficient mechanical integrity for a clinically relevant period.

[0033] In a third embodiment, the invention provides a biodegradable, biocompatible iron-based alloy composition suitable for orthopedic implants, comprising iron as the main component (at least 50 wt%) and at least one alloying element selected from manganese, zinc, and magnesium. The alloy is configured to gradually corrode in vivo while simultaneously providing bone-like mechanical support during healing.

[0034] In preferred embodiments, iron comprises at least 70 wt.%. A preferred composition includes 20-35 wt.% manganese, the remainder consisting of iron and unavoidable impurities. In such embodiments, the alloy's microstructure is predominantly a single-phase austenitic structure. A single-phase austenitic structure is preferred because it can offer improved ductility and reduce brittle behavior, while simultaneously promoting more uniform corrosion compared to multi-phase microstructures, which can cause aggressive local galvanic corrosion.

[0035] In further embodiments, the alloy comprises 1 to 10 wt% zinc and the remainder iron, such that a zinc-rich phase is dispersed in the iron matrix to form galvanic pairs that accelerate biodegradation. In other embodiments, the alloy comprises 1 to 10 wt% magnesium and the remainder iron, such that a magnesium-rich phase is present to accelerate corrosion by galvanic action. These galvanic pairs are configured to increase the corrosion rate compared to unalloyed iron, so that the implant biodegrades within a clinically relevant timeframe.

[0036] Optional embodiments include 0.1 to 1 wt.% of an alloying element selected from silver, platinum, or palladium to increase the corrosion rate of the iron-based alloy, for example, by altering the cathodic kinetics and / or microgalvanic interactions. In preferred embodiments, the iron-based alloy is essentially free of nickel, chromium, and molybdenum to avoid persistent passive layers and improve biocompatibility.

[0037] The alloy compositions can be shaped into orthopedic implant devices by machining, forging, rolling, extrusion, or additive manufacturing, followed by finishing operations. The implant can be configured as a temporary fixation element, maintaining mechanical integrity at least during an initial bone healing phase, after which controlled biodegradability reduces the implant volume and / or mass. Controlled biodegradability reduces long-term foreign body presence and can decrease the need for implant removal surgery. Examples Example 1: Magnesium alloy (Mg-Zn-Ca-Mn)

[0038] High-purity magnesium is melted under a protective atmosphere. Zinc and calcium are added to achieve a final composition of 1–5 wt% Zn and 0.1–2 wt% Ca, with magnesium comprising the remainder. Optionally, manganese is added in an amount of 0.1–1 wt%. The melt is cast into ingots and subjected to extrusion and / or rolling to refine the grain size. The resulting alloy has an α-magnesium matrix with intermetallic precipitates, including Ca₂Mg₆Zn₃, dispersed within the matrix. The average grain size is controlled to ≤ 20 µm. The alloy exhibits controlled degradation in physiological media and mechanical properties suitable for a temporary orthopedic support. Example 2: Zinc-based alloy (Zn-Mg-Ca-Sr)

[0039] Zinc is melted and alloyed with magnesium (1-10 wt%) and calcium (0.1-1 wt%), optionally with strontium (0.1-1 wt%), with zinc comprising the remainder. The alloy is cast and thermomechanically processed to create a zinc-rich matrix containing dispersed Mg₂Zn. 11 -Precipitation. Heavy metal impurities (Pb, Cd, As) are kept below 0.01 wt.%. Compared to unalloyed zinc, the alloy exhibits improved strength and a controllable biodegradation rate, making it suitable for temporary fixation. Example 3: Iron-based alloy (Fe-Mn with optional Zn / Mg)

[0040] Iron is alloyed with manganese in the range of 20–35 wt% to obtain an austenitic microstructure. In alternative variants, zinc (1–10 wt%) and / or magnesium (1–10 wt%) are added to form dispersed galvanic phases that accelerate corrosion. Optionally, 0.1–1 wt% Ag / Pt / Pd is added. The alloy is processed to produce a predominantly single-phase austenitic matrix and is essentially free of nickel, chromium, and molybdenum. The alloy provides bone-like mechanical support during healing and is configured to gradually corrode in vivo. Advantages of the invention • Offers biodegradable metallic implant compositions that can reduce the need for secondary implant removal surgery. • Ensures a balance between mechanical strength and biodegradability by controlling the composition and microstructure. • Allows selection between magnesium-, zinc- and iron-based systems, depending on the desired mining schedule and mechanical requirements. • Controls unwanted impurities (e.g., aluminum, nickel, rare earths in magnesium alloys; heavy metals in zinc alloys; Ni / Cr / Mo in iron alloys) to improve biocompatibility and corrosion predictability. • Provides microstructural properties (matrix phases and precipitates) that improve strength and support more uniform and better controlled degradation.