Magnesium-based alloys for bone regeneration and beyond: A review of advances and therapeutic prospects

Abstract

Background

Magnesium (Mg)-based alloys have gained significant attention as next-generation biodegradable biomaterials due to their bone-mimetic mechanical properties (elastic modulus: 35–45 GPa), biocompatibility, and ability to degrade in vivo without toxic byproducts.

Objective

This review systematically evaluates recent advances in Mg-based alloys for biomedical applications, focusing on orthopedic implants, cardiovascular stents, and drug delivery systems, while identifying current challenges and future research directions.

Methods

We conducted a comprehensive literature analysis of peer-reviewed studies (2019–2024) examining Mg alloy development, surface modification techniques, in vitro/in vivo performance, and clinical trial outcomes.

Results

Key findings include: (1) Alloying innovations, particularly with rare-earth elements (e.g., in WE43) and nutrient elements (Zn, Ca), have yielded alloys with bone-mimetic mechanical properties (elastic modulus: 35–45 GPa; compressive yield strength: 150–250 MPa) and decelerated degradation rates via grain refinement and secondary phase formation; (2) Surface-modified Mg stents show improved endothelialization with 30–50 % reduced restenosis rates (3) Structurally engineered Mg-based scaffolds (e.g., via additive manufacturing); enable topological control over degradation through tailored porosity; (4) Drug-eluting Mg carriers achieve sustained release kinetics, leveraging degradation to simultaneously promote tissue regeneration and deliver therapeutics. However, rapid degradation (0.2–0.5 mm/year in physiological conditions) and hydrogen gas evolution remain critical challenges.

Conclusion

Mg-based alloys show transformative potential for temporary medical implants. Future research should focus on: (1) advanced alloy design with rare-earth elements, (2) smart coating technologies, and (3) standardized long-term biocompatibility assessments to facilitate clinical translation.

1. Introduction

Magnesium-based alloys have attracted considerable interest in biomedical applications owing to their exceptional biocompatibility, low density, and favorable mechanical properties. These alloys offer a distinct advantage over conventional metallic biomaterials, particularly in terms of their biodegradability, enabling them to gradually degrade in vivo after serving their function as temporary implants. This property is particularly advantageous as it eliminates the need for secondary surgical interventions to remove permanent implants, thereby improving patient recovery and reducing healthcare burdens [1,2]. However, the rapid corrosion rate of magnesium alloys in physiological environments remains a critical challenge, as it may lead to premature loss of mechanical integrity before complete tissue healing [3,4]. Consequently, recent research efforts have been directed toward tailoring the degradation behavior and enhancing the mechanical performance of these alloys through advanced alloy design and surface modification strategies.

The application of magnesium alloys spans various medical fields, including orthopedics, cardiovascular treatments, and tissue engineering. The applications of magnesium-based implants in the medical field are partially illustrated in Fig. 1. In orthopedics, for instance, magnesium alloys are being explored as materials for bone fixation devices, such as screws and plates, due to their mechanical properties that closely match those of natural bone [5,6]. Furthermore, the release of Mg²⁺ ions during degradation plays a crucial role in stimulating osteogenesis. Mechanistically, the elevated extracellular Mg²⁺ concentration is believed to promote the influx of Mg²⁺ into osteoblasts via MagT1 transporter channels. This subsequently activates key intracellular signaling pathways, including the PI3K/AKT and ERK1/2 pathways, which upregulate the expression of osteogenic markers such as Runx2, Osterix, and Osteocalcin. Concurrently, Mg²⁺ ions can modulate the activity of transient receptor potential melastatin 7 (TRPM7) channels, further influencing cell proliferation and differentiation, thereby creating a favorable microenvironment for bone regeneration [7]. In cardiovascular applications, magnesium alloys are being developed for stents, which can provide structural support to blood vessels while gradually dissolving to prevent long-term complications associated with permanent implants [[8], [9], [10], [11]].

Fig. 1.

Partial medical applications of magnesium-based implants.

Despite their considerable potential, the clinical translation of magnesium alloys faces several critical challenges. The accelerated degradation kinetics in physiological environments often results in premature mechanical integrity loss, posing significant limitations for load-bearing orthopedic applications [12,13]. Current research focuses on multidimensional optimization strategies including: (1) strategic alloying with rare earth or zinc elements to modulate degradation rates (2) advanced surface modification techniques (e.g., plasma electrolytic oxidation), to enhance corrosion resistance, and (3) development of novel composite systems that simultaneously maintain optimal biocompatibility [14]. Furthermore, emerging fabrication technologies such as additive manufacturing (AM), specifically laser powder bed fusion (LPBF), and plasma-assisted anodization are being investigated to engineer magnesium-based implants with improved mechanical durability under complex physiological loading conditions [[15], [16], [17]].

In conclusion, magnesium-based alloys constitute a transformative class of biomaterials that present groundbreaking opportunities for addressing contemporary limitations in medical implant technology. To fully harness their clinical potential and facilitate successful translational implementation, sustained multidisciplinary research efforts remain imperative. This comprehensive review systematically examines cutting-edge developments in magnesium alloy innovation, critically assesses their therapeutic applicability across diverse medical specialties, and proposes strategic research trajectories to guide future advancements in this burgeoning field.

2. Basic properties of magnesium-based alloys

Magnesium-based alloys have garnered significant attention in recent years due to their unique properties that make them suitable for various biomedical applications. These alloys are lightweight, possess high specific strength, and exhibit excellent biocompatibility, making them ideal candidates for biodegradable implants. However, their rapid degradation rates in physiological environments pose challenges that need to be addressed through alloying and surface modifications. Fig. 2 schematically illustrates the factors influencing the degradation of magnesium alloys in physiological media. The combination of these properties positions magnesium alloys as promising materials for applications in orthopedic and cardiovascular devices, where they can provide structural support while gradually dissolving in the body, thus eliminating the need for secondary surgeries for implant removal [1,16].

Fig. 2.

Schematic representation of Mg-based alloys, including the experimental setup for degradation tests, the corrosion mechanism in physiological environments, and the role of alloying elements in controlling degradation while maintaining mechanical integrity.

2.1. Physical and chemical properties

The physical and chemical properties of magnesium-based alloys are critical in determining their suitability for medical applications. Magnesium has a low density, which contributes to its lightweight nature, making it advantageous in reducing the overall weight of implants. Its mechanical properties, such as tensile strength and yield strength, can be significantly enhanced through alloying with elements like zinc, calcium, and rare earth elements. These modifications not only improve mechanical performance but also influence the corrosion behavior of the alloys. The corrosion resistance of magnesium alloys is a double-edged sword; while they degrade at a controlled rate, excessive corrosion can lead to premature loss of mechanical integrity. Therefore, understanding the electrochemical behavior of these alloys in biological environments is essential for optimizing their performance [[5], [6], [7]].

2.2. Biocompatibility

Biocompatibility is a crucial factor for any material intended for medical implants. Magnesium alloys exhibit favorable biocompatibility due to their ability to promote osteogenesis and their low toxicity levels. The degradation products of magnesium, such as magnesium ions, can enhance bone healing by stimulating osteoblast activity while inhibiting osteoclast formation, thus facilitating bone remodeling. However, the rapid degradation of magnesium alloys can lead to localized hydrogen gas formation, which may cause complications. Researchers are actively exploring various surface modifications and alloying strategies to enhance biocompatibility while controlling the degradation rate. For instance, coatings of hydroxyapatite or biopolymers have shown promise in improving the biocompatibility of magnesium alloys by providing a more favorable environment for cell adhesion and proliferation [18,19]. Furthermore, inorganic coatings like magnesium fluoride (MgF₂) have been widely investigated [38], forming a dense barrier that effectively decelerates the degradation rate of Mg alloys in physiological environments.

2.3. Mechanical properties

The mechanical properties of magnesium-based alloys are paramount for their application in load-bearing implants. These alloys typically exhibit a combination of high strength and ductility, which is essential for withstanding the mechanical loads encountered in the human body. For instance, the compressive yield strength of commonly researched Mg-Zn-Ca alloys ranges from 150 MPa to 250 MPa, with an elastic modulus of 35–45 GPa, closely matching that of cortical bone (∼10–30 GPa modulus, 130–180 MPa strength) and thereby minimizing stress shielding [20,21]. In contrast, the yield strength of WE43 alloys can exceed 250 MPa after appropriate thermo-mechanical processing [15,16]. The incorporation of specific rare earth elements (e.g., Yttrium in WE43) has been shown to enhance strength primarily through solid solution strengthening and precipitation hardening mechanisms. Additionally, processes such as extrusion and forging can improve the microstructure, leading to better mechanical properties. However, challenges remain in balancing strength with corrosion resistance, as higher strength often correlates with increased brittleness. Ongoing research aims to optimize these properties through advanced processing techniques and innovative alloy compositions [18,41,42].

In conclusion, magnesium-based alloys present a compelling option for biomedical applications due to their lightweight, biocompatible, and mechanically favorable properties. Continued advancements in alloy design and surface treatments are essential to overcome the challenges posed by their rapid degradation rates, ensuring their successful integration into clinical practice.

3. Magnesium-based alloys in bone repair applications

Magnesium-based alloys have emerged as promising materials for bone repair due to their unique combination of biocompatibility, biodegradability, and mechanical properties that closely match those of natural bone. These alloys are particularly advantageous for applications in orthopedic implants, where the need for materials that can support bone healing while gradually degrading in the body is critical. The inherent properties of magnesium allow for the controlled release of magnesium ions, which have been shown to enhance osteogenesis and promote bone tissue formation. The unique advantages of magnesium alloys for orthopedic implants are illustrated in Fig. 1. As depicted, a traditional bio-inert implant (e.g., titanium) merely provides mechanical support and may lead to stress-shielding over time. In contrast, a biodegradable Mg-based implant provides initial mechanical stability and then gradually degrades, synchronizing with the bone healing process. Concurrently, the release of Mg²⁺ ions stimulates new bone formation (osteogenesis) and vascularization, ultimately resulting in complete regeneration of the bone defect without the need for a secondary removal surgery. This combination of biodegradability and bioactivity is a key benefit that makes Mg a superior candidate for next-generation orthopedic applications. As a result, magnesium alloys are being actively researched and developed as alternatives to traditional metallic implants that often necessitate secondary surgeries for removal, thereby reducing patient morbidity and healthcare costs [1,2].

3.1. Bone defect repair

The application of magnesium-based alloys in the repair of bone defects has garnered significant attention in recent years. These alloys exhibit favorable mechanical properties. As noted in Section 2.3, their compressive yield strength (150–250 MPa) and elastic modulus (35–45 GPa) are comparable to those of human cortical bone (∼130–180 MPa strength, 10–30 GPa modulus [3,4]), thus minimizing the risk of stress shielding—a common issue associated with traditional metallic implants (e.g., Ti-6Al-4V alloy with modulus ∼110 GPa [7]). However, a critical challenge remains in balancing this mechanical integrity with corrosion resistance. For example, while alloying with elements like Zn and Ca improves strength, excessive addition (e.g., Zn > 4 wt%) can accelerate degradation due to increased secondary phase formation [5,6]. Recent advances aim to achieve a degradation rate below 0.5 mm/year in simulated body fluid while maintaining the aforementioned mechanical properties, a key target for orthopedic applications [7]. Studies have demonstrated that magnesium-based implants can effectively support the healing process in critical-sized bone defects by providing a scaffold that facilitates new bone formation. Furthermore, the biodegradability of magnesium alloys allows for a gradual replacement by newly formed bone tissue, eliminating the need for surgical removal of the implant. Research indicates that the degradation products of magnesium, including magnesium ions, can stimulate osteoblast activity while inhibiting osteoclast formation, thereby promoting a favorable environment for bone regeneration [6,7,35].

3.2. Design and optimization of bone implants

The design and optimization of magnesium-based bone implants are crucial for their success in clinical applications. Researchers are focusing on enhancing the mechanical properties and corrosion resistance of these alloys through various methods, including alloying with other elements, surface modifications, and advanced manufacturing techniques. For example, the Mg-2Zn-0.5Ca alloy system has shown particular promise for orthopedic applications, exhibiting a compressive yield strength of ∼210 MPa and a reduced degradation rate compared to pure Mg, making it suitable for load-bearing bone implants [20,21]. The incorporation of specific rare earth (RE) elements, such as Gadolinium (Gd), Yttrium (Y), and Neodymium (Nd), has been strategically employed to enhance the strength and ductility of magnesium alloys. These elements primarily function through solid solution strengthening and grain refinement mechanisms. For instance, Gd exhibits significant solid solubility in Mg, leading to pronounced solution strengthening effects, while Y and Nd are effective in forming secondary phases that impede grain boundary movement, thereby refining the microstructure and improving mechanical properties [[18], [19], [20], [21]]. Additionally, innovative fabrication techniques, such as additive manufacturing, allow for the creation of complex geometries and tailored porosity in magnesium implants, which can enhance their integration with surrounding bone tissue and improve overall healing outcomes. These advancements in design and optimization are essential for addressing the challenges associated with the rapid degradation rates of magnesium alloys, which can lead to premature loss of mechanical integrity [7].

3.3. Clinical trials and research outcomes

Clinical trials investigating the use of magnesium-based alloys for bone repair have shown promising results, further validating their potential as effective biomaterials. Several studies have reported successful outcomes in preclinical and clinical settings, demonstrating that magnesium implants can enhance bone healing and integration while minimizing complications associated with traditional implants. For example, trials involving magnesium alloy screws and scaffolds have indicated effective bone regeneration in models of critical-sized defects, with favorable histological and radiological outcomes [1,2]. Furthermore, ongoing research is exploring the long-term biocompatibility and mechanical performance of these alloys in diverse patient populations, which is essential for their broader clinical adoption. As more data becomes available from clinical trials, the understanding of the mechanisms by which magnesium alloys promote bone healing will continue to evolve, paving the way for their implementation in routine clinical practice [3,4].

4. Magnesium-based alloys in cardiovascular implants

Magnesium-based alloys have emerged as promising materials for cardiovascular implants due to their unique combination of biocompatibility, biodegradability, and mechanical properties. These alloys are particularly attractive for applications such as stents, where the ability to degrade over time can reduce the need for additional surgeries to remove permanent implants. The mechanical strength of magnesium alloys is comparable to that of traditional metallic implants, making them suitable for load-bearing applications [21]. However, their rapid corrosion rates in physiological environments pose significant challenges, necessitating ongoing research into surface modifications and alloy compositions to optimize their performance in clinical settings [12,13,26].

4.1. Selection of stent materials

The selection of stent materials is critical in the design and functionality of cardiovascular implants. Magnesium alloys, particularly those alloyed with elements such as zinc and calcium, have shown potential for enhancing the mechanical and biological properties of stents. The choice of alloying elements can significantly influence the corrosion rate, mechanical strength, and biocompatibility of the stents. For instance, the incorporation of rare earth elements has been found to improve the mechanical properties and reduce the degradation rates of magnesium alloys, thus enhancing their suitability for long-term applications in cardiovascular interventions [[22], [23], [24], [25]]. Additionally, the development of coatings, such as magnesium fluoride, can provide an effective barrier against corrosion while promoting endothelialization, which is crucial for the successful integration of stents into the vascular system [5,6,26,27].

4.2. Advantages of biodegradable stents

Magnesium alloys are biodegradable and eliminate the need for a second surgery, a significant advantage over permanent implants like stainless steel or titanium. This is particularly beneficial for patients who are at risk of complications from prolonged exposure to non-degradable materials. The degradation products of magnesium, such as magnesium ions, are known to have positive effects on bone healing and vascular function, promoting tissue regeneration and reducing inflammatory responses [18,19,[28], [29], [30], [31]]. Furthermore, biodegradable stents can minimize the risk of late thrombosis, a common complication associated with permanent stents, by allowing the natural healing process of the vessel to proceed without the interference of foreign materials [[1], [2], [3], [4]]. The ability to tailor the degradation rate of magnesium alloys through alloying and surface treatments further enhances their applicability in various clinical scenarios [20,21,[23], [24], [25]].

4.3. Clinical case analysis

Clinical applications of magnesium-based stents have demonstrated their potential in treating cardiovascular diseases. Several studies have reported successful outcomes with biodegradable magnesium stents, highlighting their ability to support vascular healing while gradually degrading in situ. For instance, clinical trials have shown that patients receiving magnesium alloy stents experience favorable healing responses, with reduced incidences of restenosis and thrombosis compared to those with permanent stents [[23], [24], [25],[32], [33], [34]]. Moreover, the use of magnesium-based stents has been associated with improved endothelial function and reduced inflammatory responses, further supporting their clinical efficacy [1,2,[23], [24], [25]]. As research continues to refine the properties of these materials and optimize their performance, magnesium-based alloys are poised to play a significant role in the future of cardiovascular implant technology.

5. Applications of magnesium-based alloys in drug delivery systems

Magnesium-based alloys have emerged as promising materials in the field of drug delivery systems due to their unique combination of biocompatibility, biodegradability, and mechanical properties. These alloys can serve as drug carriers, allowing for localized and controlled release of therapeutic agents. The inherent properties of magnesium, such as its ability to degrade in physiological environments and release magnesium ions, contribute to its potential in enhancing drug delivery efficacy. Furthermore, the degradation products of magnesium, which include hydroxyl ions, can create an alkaline environment that promotes tissue healing and regeneration, making magnesium alloys an attractive option for various biomedical applications, particularly in orthopedic and cardiovascular fields [[1], [2], [3], [4]].

5.1. Design of drug carriers

The design of drug carriers based on magnesium alloys involves several critical considerations to optimize their performance in drug delivery applications. These include the selection of appropriate alloy compositions, surface modifications, and the incorporation of drug loading mechanisms. Recent studies have focused on creating magnesium-based composites for controlled drug release. For instance, Qi et al. [35] developed a simvastatin-loaded gelatin nanosphere/chitosan coating on Mg alloy via electrophoretic deposition. This system not only significantly enhanced corrosion resistance but also demonstrated a sustained release profile over 14 days, effectively promoting osteogenic differentiation and vasculogenesis in co-culture models. Similarly, Pan et al. [23] engineered a sodium alginate/carboxymethyl chitosan coating on Mg alloys that catalytically releases nitric oxide (NO), a bioactive molecule that improves hemocompatibility and accelerates endothelialization for vascular stent applications. For instance, the use of magnesium-lithium alloys has shown promise in achieving a balance between mechanical integrity and degradation rates suitable for drug delivery [1,2]. Additionally, surface coatings can be applied to magnesium alloys to improve their corrosion resistance and biocompatibility, further enhancing their suitability as drug carriers. The development of biodegradable coatings, such as those incorporating gelatin or chitosan, allows for sustained drug release while minimizing adverse effects on surrounding tissues [[35], [36], [37], [38], [39]]. Overall, the design of magnesium-based drug carriers is a multifaceted process that requires careful consideration of material properties, drug interactions, and the physiological environment.

5.2. Drug release mechanisms

Understanding the mechanisms of drug release from magnesium-based carriers is crucial for optimizing their therapeutic efficacy. The release of drugs can occur through several mechanisms, including diffusion, erosion, and degradation of the carrier material. For magnesium alloys, the degradation process is particularly significant, as it not only facilitates drug release but also contributes to the therapeutic effects of the released magnesium ions. The degradation of magnesium in physiological environments leads to the formation of hydroxyl ions and hydrogen gas, which can enhance the local pH and promote tissue healing [40]. Studies have demonstrated that drug release profiles can be tailored by adjusting the alloy composition, surface treatments, and the presence of additional polymers or coatings that modulate the degradation rate [7]. Furthermore, the interplay between the drug properties and the carrier's degradation behavior can influence the release kinetics, making it essential to design carriers that can provide the desired release profiles for specific therapeutic applications.

5.3. Research progress and challenges

Despite the promising applications of magnesium-based alloys in drug delivery systems, several challenges remain that need to be addressed to facilitate their clinical translation. Research has made significant strides in understanding the biocompatibility and degradation behavior of magnesium alloys; however, issues such as rapid degradation rates and the potential for localized hydrogen gas accumulation still pose challenges in clinical settings [12,13]. Additionally, the mechanical properties of magnesium alloys must be optimized to ensure they can withstand physiological loads during the healing process without premature failure. Ongoing research efforts are focused on alloying magnesium with other metals, such as zinc and calcium, to improve its mechanical performance and control degradation rates [20,21]. Multiscale degradation modeling of magnesium-based implants still faces several challenges, including incomplete fundamental theories and missing key parameters. Uncertainty quantification techniques offer potential solutions for estimating these unknown parameters, such as the Kriging algorithm. As illustrated in Fig. 3, inherent uncertainties exist in the degradation models of magnesium-based implants. The accumulation of uncertainties across different stages can significantly compromise the model's predictive capability. Therefore, systematic identification and quantification of the total uncertainty in the system are essential to enhance model reliability. Furthermore, the development of innovative surface coatings and composite materials is being explored to enhance the functionality of magnesium-based carriers while minimizing adverse reactions in vivo [38,39]. As the field continues to evolve, interdisciplinary collaboration between materials science, pharmacology, and clinical medicine will be essential to overcome these challenges and fully realize the potential of magnesium-based alloys in drug delivery applications.

Fig. 3.

Uncertainty propagation in the degradation model of magnesium-based implants. The cumulative effect of uncertainties arising from individual modeling stages diminishes the overall predictive capability of the model.

6. Future research directions of magnesium-based alloys

Magnesium-based alloys have gained significant attention in the biomedical field due to their promising properties such as biocompatibility, biodegradability, and mechanical strength. However, to fully harness their potential, future research must focus on several key areas that address current limitations and explore innovative applications.

6.1. Exploration of new alloy compositions

The development of new alloy compositions is critical for enhancing the performance of magnesium-based materials in biomedical applications. Research has shown that incorporating various alloying elements can significantly improve the mechanical properties, corrosion resistance, and biocompatibility of magnesium alloys. For instance, the addition of rare earth elements (REEs) has been highlighted as a promising approach to enhance the mechanical and biological properties of magnesium alloys, which could lead to better outcomes in clinical applications [18,19]. Additionally, studies have explored magnesium-based composites, such as Mg-9Li and AZ31B alloys with tungsten carbide reinforcements, which demonstrate improved strength and wear resistance, making them suitable for medical joint replacements [3,4]. The ongoing exploration of novel alloy compositions, including combinations of magnesium with zinc and calcium, will be pivotal in addressing the challenges of rapid biodegradation and mechanical integrity, ultimately leading to more effective biodegradable implants.

6.2. Innovations in fabrication techniques

Advancements in fabrication techniques are essential for the successful application of magnesium alloys in biomedical settings. Traditional manufacturing methods often struggle to produce complex geometries or achieve the required surface properties for optimal performance. Innovative techniques such as selective laser melting (SLM) and additive manufacturing have emerged as promising solutions, allowing for the production of intricate structures with controlled porosity and mechanical properties [41,42]. Furthermore, surface modification techniques, including coatings and alloying treatments, are being developed to enhance corrosion resistance and biocompatibility, which are crucial for the longevity and effectiveness of magnesium implants [43]. Research into these innovative fabrication methods will not only improve the mechanical performance of magnesium alloys but also facilitate their integration into clinical applications, thereby expanding their use in regenerative medicine and orthopedic implants.

6.3. Clinical applications: prospects and challenges

The clinical application of magnesium-based alloys presents both promising prospects and notable challenges. The inherent biodegradability of magnesium alloys allows for their use as temporary implants that can support tissue healing without the need for surgical removal [44]. However, the rapid degradation rates of these materials can lead to premature loss of mechanical integrity, which poses a significant challenge in load-bearing applications [45,46]. Addressing these issues requires a multifaceted approach, including the development of alloys with tailored degradation rates and the incorporation of bioactive coatings to enhance tissue integration and reduce inflammatory responses [7]. Furthermore, extensive preclinical and clinical studies are needed to establish the safety and efficacy of these materials in various medical contexts, including orthopedic and cardiovascular applications [47]. As research progresses, overcoming these challenges will be crucial for the successful translation of magnesium-based alloys from the laboratory to clinical practice, ultimately improving patient outcomes in regenerative medicine.

7. Conclusion

Magnesium-based alloys show exceptional promise in medical applications, including bone repair, cardiovascular implants, and drug delivery, due to their biocompatibility, biodegradability, and bone-mimetic mechanical properties. However, clinical translation faces challenges in controlling degradation kinetics, ion release effects, and corrosion-mechanical balance to ensure therapeutic efficacy and biosafety.

Advancing these materials requires interdisciplinary collaboration to optimize alloy design and surface modifications, addressing limitations like inflammatory responses and mechanical instability. Future progress hinges on deeper understanding of biological interactions and leveraging emerging technologies to tailor alloys for specific applications.

Despite current hurdles, magnesium alloys hold transformative potential for medical devices, with continued research poised to bridge laboratory innovation to clinical practice.

Section I

The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial inter- est (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Section II

The authors whose names are listed immediately below report the following details of affiliation or in- volvement in an organization or entity with a financial or non-financial interest in the subject matter or materials discussed in this manuscript. Please specify the nature of the conflict on a separate sheet of paper if the space below is inadequate.

Authorship

Lu-Hang Xu, Conception and design of study, Drafting of manuscript and/orcritical revision; Li-Tian Ye Conception and design of study, Jia-Yu Wang Conception and design of study, Xuan Qiu Conception and design of study Drafting of manuscript and critical revision Approval of final version of manuscript

Funding

This research was supported by the Linglong Yingcheng Hospital Original Foundation (YCYY2023ZZ002).

Declaration of competing interest

The authors declare that there is no conflict of interest.