Influence of Metal Processing on Microstructure and Properties: Implications for Biodegradable Metals—A Mini Review

Abstract

Biodegradable metallic alloys are currently being explored extensively for use in temporary implant applications, since the prolonged existence of implants within the body has been linked with health complications and metal toxicity. There are many metal alloy fabrication methods available in the industrial, aerospace, and biomedical fields; some of them have more advanced techniques and specialized equipment than others. Past studies have shown that the performances of materials is greatly affected by the concentration of alloying elements and the metal processing techniques used. However, the impact each fabrication method has on the chemical and mechanical properties of the material is not fully understood; this lack of knowledge limits the advancement of the field of biodegradable metals. This review provides a general introduction to biodegradable metals and their applications and then aims to give a broad overview of the influence of metal processing on the microstructure and properties of metal alloys. The possible implications of these fabrication methods for the biodegradable metals are discussed.

1. Introduction

Biomaterials are materials that are engineered to interact with biological systems for medical or therapeutic purposes [1]. To be accepted as a biomaterial, the element or compound must safely integrate into the living organism and perform its intended function without harming the host. Metals as a class of biomaterials have been used extensively in the biomedical field [2]. Their applications range from long-term bone and joint replacements, where they showcase an exceptional load-bearing capacity [3], to temporary cardiovascular stents exhibiting good hemocompatibility and excellent soft-tissue support [4]. The use of metallic materials to replace or support injured tissue has been traced back to ancient times. One of the earliest such applications was the use of gold in dentistry as a tooth replacement, which was referenced in China in the seventh century AD [5]. However, the surgical implantation of biomaterials was not safe nor practical until the 1860s, when Joseph Lister invented an antiseptic technique that could control infection during and after the operation [6]. Although some metal implants have improved in biocompatibility since then, metallic materials were still lacking in terms of mechanical performance and corrosion resistance. In response to this lack, pure metals were engineered and alloyed with other elements to improve their biocompatibility, strength, durability, and other physical and chemical properties [7].

In 1912, vanadium steel was developed for use in the manufacturing of bone fracture plates and screws; this was the first successful attempt at fabricating a metallic material tailored specifically for a biomedical implant application [8]. Nonetheless, the use of this material was restricted shortly after its discovery due to implant dysfunctionality characterized by poor biocompatibility, inadequate in vivo corrosion resistance, and mechanical failure [9].

The limitation of vanadium steel’s biocompatibility is attributed to the percentage of vanadium in the alloy, which was classified as a toxic metal along with chromium, nickel, cobalt, and many other heavy metals [10]. The mentioned heavy metals are normally avoided for their adverse effects on the biological system. A tremendous effort has been put into studying the biodynamic activity of materials since the discovery of vanadium steel. Biomaterials were later divided into biotolerant, bioinert, and bioactive; this can be determined through in-depth investigation and controlled in vivo testing [11]. Biotolerant materials react in the biological environment causing the surrounding tissue to form a fibrous layer encapsulating the implant. However, the implant is not rejected by the body and can still serve its purpose (most metals are categorized as biotolerant) [12]. Bioinert materials, on the other hand, are known for not initiating any bodily response and are not reactive in the biological environment, such as titanium, zirconia, and alumina. In contrast, bioactive materials are known to react with surrounding tissue forming chemical bonds between the interface of the material and the tissue [11]. Bioactive materials include ceramics and bioactive glasses. The mentioned bioactive materials are used as coatings to enhance the bioactivity properties of implantable biometals.

Another way to enhance metals’ properties in order to meet the benchmark for biomedical applications is through alloying [13]. Metal alloys are combinations of two or more elements, one of which must be a metal. The mixing of these elements results in a material with properties different from those of the individual components [14]. A thorough understanding of the behavior of each alloy component is needed to be able to manipulate the composition producing biomaterial that fits the constraints of its designed purpose. The interaction of the atoms of these elements in the crystal lattice dictates the properties of the resultant material [15]. In the case of substitution alloys, the atomic radii of the solvent and solute must be of similar size for an atomic exchange to occur in the crystal lattice. For the interstitial alloy, the atomic radius of the solute must be significantly smaller than the atomic radius of the solvent metal, so that smaller atoms can be situated between the atoms of the solvent achieving the interstitial alloy. Some ternary alloys (composed of three elements) with varying atomic sizes display interstitial and substitutional arrangements of atoms [15]. Figure 1 is an illustration of different atom arrangements in a metallic crystal lattice.

Aside from adding alloying elements and impurities to pure metals, the refinement of biometals’ properties can also be performed through cold or hot working [16]. Metal forming methods could potentially cause a distortion in the lattice structure [17]. Lattice distortions can be defined as the disruption that occurs to the natural arrangement of atoms in a crystal lattice [18]. These changes in lattice parameters significantly affect the way metals deform under stress and alter the chemical and physical performance of a material [15]. Numerous studies have been dedicated to examining and controlling the formation of disruptions in the crystal structure of metals to achieve higher strength and hardness. Yet, excessive distortion yields a material with poor ductility [19]. The choice of alloying elements and processing methods is greatly influenced by the engineering requirement of metallic biomaterial and targeted application. Hence, a comprehensive examination of these factors must be performed well in advance of the fabrication of new biometals.

The main complication related to the use of metallic implants is the corrosion susceptibility of the biometal used. Implants are exposed to a harsh biological environment and come into direct contact with corrosive biological media [20]. The type of corrosion is specific to the nature of the implantation site as well as the proposed function of the implant. For instance, fretting corrosion, which is also known as mechanically-assisted corrosion, occurs on the contact surface of the material due to friction and slight movements. Fretting corrosion has been reported for hip implants [21]. Pitting corrosion, on the other hand, is localized corrosion associated with the formation of small cavities on the surface of the implant [22]. It has been discovered that 316 L stainless steel is one of the most susceptible biomaterials to pitting corrosion [20]. The galvanic process is an electrochemical process that occurs when two types of metals with different electrochemical potentials come in proximity. Galvanic corrosion can be detected with orthopedic screws and plates if fabricated with different types of metals [20]. While corrosion could be a direct cause of implant failure, the natural corrosion process of some metals can be employed to carry out a specific function in the biological body and degrade when its mechanical support is no longer needed.

2. Biodegradable Metal Application

2.1. Stenosis and Stenting

Stenosis is a medical condition where the arteries narrow, restricting blood flow to the heart. This can be caused by plaque buildup or other diseases, and can lead to serious health complications, such as heart attacks, strokes, or other cardiovascular diseases. Age, genetics, and lifestyle choices are the main factors contributing to this disease [23]. Over the years, different methods have been employed to manage coronary artery disease. The first method developed for treatment involved the use of percutaneous transluminal coronary balloon angioplasty, which was reported to assist in attaining a luminal diameter that is large enough to permit blood flow through the process of plaque extrusion [24]. Angioplasty was seen as a viable solution in complex cases in which major surgeries were determined to be too risky for patients. Along with its many benefits, this method had its downsides, including recoil of the blood vessel, aggregation of platelets, and thrombosis [25]. As a result of these limitations, researchers and investigators dedicated tremendous efforts to finding alternative solutions that can revolutionize the way coronary artery diseases are treated. These efforts gave rise to what is today known as stents.

Stents are mesh-like tubes that can be inserted into arteries to dilate them when narrowed or clogged [26]. The implantation of the first stent was a milestone, set by Puel and Sigwatt in 1986, when they independently implanted a self-expanding coronary stent [27]. A year later, the Palmaz stent was introduced; this is a balloon-expandable stainless-steel stent and was the first stent to be approved in the United States [25]. Aside from the original bare-metal stents, stents went through many developmental stages, such as the drug-eluting stent, where a coating is applied to the surface of the stent to control the release of therapeutic agents, such as anti-proliferative and anti-thrombotic drugs, and biodegradable stents, which corrode and dissolve safely in the biological environment after the assigned artery remodeling period has passed [28]. Regardless of the type and the unique function of the stent implanted, there are fundamental design constraints for this application that all types of stents must conform to. These constraints are detailed in

Table 1. Design requirements for biodegradable stents [28,29,30].

	Criterion
Specific design constraints	Biocompatibility	Mechanical integrity	Mechanical properties	Corrosion behavior
	Non-toxic, non-inflammatory, hypoallergenic	Mechanical integrity 3–6 months	Yield strength >200 MPa	Penetration rate <20 $\mathsf{\mu }\mathrm{m}/\mathrm{y}\mathrm{e}\mathrm{a}\mathrm{r}$
	no harmful release or retention of particulates	Full absorption in 1–2 years	Tensile strength >300 MPa	Hydrogen evolution <$10 \mathsf{\mu }\mathrm{L}/\mathrm{c}{\mathrm{m}}^2$ per day
	Promote endothelial cell attachment and discourage smooth muscle cell attachment, as they have a negative effect on vessel patency		Elongation to failure >15–18% Higher ductility is ideal for higher flexibility, but need enough radial force to open lesions
			Elastic recoil on expansion <4%
			Low elastic modulus

.

2.2. Orthopedic Internal Fixation Devices

Orthopedic fixation devices are implants in the form of plates, pins, wires, and screws used to stabilize fractured bone and to guide the healing process and support the weight of the body enabling the use of the limb at early stages of the injury [31]. The concept of fracture management goes back to ancient Egypt [32]. However, the first documentation of the use of fixation devices in the literature was in the late 18th century by Carl Hansmann [33]. The need for internal fixation devices increased after World Wars I and II; during this period, fixation devices gained considerable attention [34]. The first models of internal fixation devices were made out of inert metals such as stainless steel and titanium [35]. The use of such materials caused some concerns regarding the possible migration of the implant, the growth restrictions in pediatric applications, the need for removal operation, and the interference of these implants in imaging techniques. The limitations of rigid fixation devices were overcome in 1966 with the emergence of biodegradable devices [36]. Since the introduction of biodegradable internal fixation devices, exceptional effort has been performed to tailor the mechanical properties and degradation rate for fixation implants to achieve an adequate load-bearing capacity and a degradation rate equivalent to bone growth [31]. The specific design constraints for biodegradable orthopedic fixation devices are detailed in

Table 2. Design requirements for biodegradable orthopedic internal fixation devices [29,30].

	Criterion
Specific design constraints	Biocompatibility	Mechanical integrity	Mechanical properties	Corrosion behavior
	Non-toxic, non-inflammatory, hypoallergenic	Mechanical integrity >6 months	Yield strength >230 MPa	Plate and screws Corrosion rate 0.5 mm/year
	no harmful release or retention of particulates	Full absorption in 1–2 years	Tensile strength >300 MPa	Hydrogen evolution < $10\mathsf{\mu }\mathrm{L}/\mathrm{c}{\mathrm{m}}^2$ per day
	promote osteoblast adhesion proliferation		Elongation to failure >15–18%
	Avoid fibrous encapsulation		Elastic modulus 10–20 GPa, as close to cortical bone as possible to avoid stress-shielding

.

The understanding of the design constraints and application-specific requirements helps guide the fabrication and refinement process of biodegradable metals, thus ensuring that the assigned materials meet the necessary criteria and avoiding engineering failures and postsurgical complications.

3. Biodegradable Metals

In the literature, the words degradable, bioresorbable, and absorbable are used interchangeably. Nonetheless, the definitions of these three terms differ. Biodegradability is the ability of a biomaterial to decompose in a non-toxic matter in the biological body after serving its designed purpose while bioresorbable and absorbable materials are naturally absorbed by the biological system, hence the name [37]. Throughout this paper, the three terms will be used in reference to the natural corrosion process of biometals in the human body. The degradation rate of these materials should be strictly controlled to ensure no inflammation or toxicity is caused to the system [38]. Biodegradable implants must maintain their durability and provide the mechanical support needed to support the healing process. This suggests that the degradation rate of the material should match the healing rate of the injured tissue which draws the map for choosing the most suitable material for each application [39]. Iron, magnesium, and zinc have been extensively studied as biodegradable metals in the past years. These metals are trace elements that are essential for the proper functioning of the human body, thus reasonable amounts of these elements are non-toxic and do not evoke an immune response [40]. Although Fe, Mg, and Zn were claimed to be acceptable in various applications, each metal has its desirable features as well as its notable limitations.

3.1. Iron and Iron-Based Alloys

Iron (Fe) is a crucial mineral that supports the body’s natural processes. It is a key component of hemoglobin and an essential element for the transportation of oxygen. Iron deficiency results in insufficient transportation of oxygen, leading to fatigue and other health problems [41]. The numerous health benefits of Fe encouraged its use as a biomaterial. Iron and iron-based alloys are known for their strength, hardness, and ductility. Their properties are comparable to 316 L stainless steel which makes Fe-based alloys favorable for temporary load bearing and for applications where strength and durability are paramount [42]. Nonetheless, the degradation rate of iron was determined to be extremely slow with irregular in vivo corrosion. The localized corrosion of iron could cause a sudden mechanical failure [43]. The major limitations that were revealed using biodegradable Fe led researchers to alloy iron with other metals which could potentially refine its degradation performance or look for better alternatives in Mg or Zn. One of the recent techniques that have been utilized to accelerate the biocorrosion rate of iron was reported in 2022. High-purity tantalum was deposited onto an iron substrate using a magnetron sputtering technique with a vacuum pressure of $5\times {10}^{-4}$ Pa and 50 W power. A negative voltage of −1000 V was applied to the iron substrate maintaining a working temperature of 25 °C and a pressure of 0.6 Pa. The differences in performance between bare Fe and tantalum-implanted surface nanostructure were closely examined both in vitro and in vivo using a rabbit femoral defect model [43].

Figure 2 above shows the result for up to 28 days of in vitro immersion tests for pure Fe samples and Ta-implanted Fe samples. It is reflected in the results that the implantation of Ta significantly increased the degradation rate of iron; this also resulted in a notable increase in ion concentration. The thickness of corrosion byproducts also experienced a slight increase. It was claimed in this article that although the corrosion rate and ion concentration of Fe witnessed a drastic increase, the biocompatibility and non-toxicity of the material were not affected. This was validated by the in vivo result. It was found that nano Ta–Fe should have exceptional biocompatibility, but also promoted osteoblast spread and adhesion on the surface of the implant, maintained its mechanical integrity for up to 40 weeks, and showed an excellent degradation uniformity [43].

3.2. Magnesium and Magnesium Based Alloys

Magnesium is another vital dietary mineral. It is essential for nerve and muscle function, healthy bones, and a healthy cardiovascular system. It was claimed that the corrosion products of Mg implants are safely absorbed by the metabolic system and surrounding tissue, which made Mg and Mg-based alloys increase in popularity for use in the biomedical industry [44]. Furthermore, past studies have reported that Mg possesses good mechanical strength and ductility, yet the mechanical integrity of magnesium is rapidly compromised under physiological conditions [45]. The high corrosion rate of Mg does not only cause the implant to lose its function, but it also imposes a threat to surrounding tissue by overwhelming the system with higher concentrations of Mg ions causing a drastic change in the pH value [46]. In a study examining the effect of the degradation behavior of magnesium, a pure Mg implant was placed as a bone fixation device in rats. It was discovered that the fast degradation rate of magnesium resulted in hydrogen gas evolution. The ${\mathrm{H}}_2$ formed cavities that spread and caused bodily swelling, dislocation of the implant, and distressed the whole biological system. The complications resulting from the fixation implant reduced the rat’s post-implantation survival rate [47]. Among the many actions performed to enhance the mechanical properties (MP) and decrease the corrosion rate of Mg, Marta Mohedano and her colleagues alloyed gallium (Ga) from 1 to 4 wt.% with pure magnesium. Their findings show that the addition of Ga refined the grain size, resulting in a minor increase in the hardness value where a maximum hardness was 53 $\pm$ 4 HV recorded for Mg–4Ga and increased second phase ${\mathrm{Mg}}_5{\mathrm{Ga}}_2$ which was linked to the increase in Ga wt.%. Furthermore, it was observed that all Mg–Ga alloys exhibited similar corrosion behavior when subjected to shorter immersion periods. However, longer immersion times revealed that higher concentrations of Ga cause an increased corrosion rate, which was validated by mass loss and hydrogen evolution measurements [48]. Recent studies have shown evidence that the manipulation of the microstructure and grain size of magnesium alloys can also improve their mechanical and corrosion behavior. A study published in 2022 investigated the effect of high-pressure torsion (HPT) and thermal treatment on the corrosion process of Mg-based alloys. It was concluded that HPT encourages the formation of special structures in Mg–1Zn–0.2Ca and Mg–1Ca alloys, thus decreasing the potential difference between the anode ($\mathrm{M}{\mathrm{g}}_2\mathrm{C}\mathrm{a})$ and the cathode ($\alpha -\mathrm{Mg})$ by controlling the dispersion of eutectics region and avoiding the dissolution of large regions of the anode that cause surface pitting and corrosion propagation. Post-HPT annealing resulted in a conversion of [49].

3.3. Zinc and Zinc-Based Alloys

3.3.1. Pure Zinc

Zinc is an essential trace element needed for DNA and RNA synthesis and repair. It is involved in immune system support and numerous enzymic reactions. It also has an anti-cancer effect owing to its antioxidant properties [50]. Although it is the most recent addition to the investigated biodegradable metals, its minimal reactivity, low melting point, and good machinability led to Zn and its alloys capturing the attention of many researchers [51]. Due to the degradation-related limitations faced by Fe, Mg, and their alloys, Zn became an attractive candidate for temporary implant application. The corrosion rate of zinc was determined to be higher than that of Fe and lower than the corrosion rate of Mg [52]. The only drawback of using zinc as a biomaterial is its poor mechanical performance which does not meet the benchmark for clinical applications. The properties of a metal can typically be improved by metal processing and mechanical working or by alloying and adding impurities. The mechanical properties of as-cast pure zinc were investigated, and it was stated that as-cast pure zinc had a yield strength (YS) of 10.14 MPa, tensile strength (TS) of 18.25 MPa, and 0.32% ductility [53]. Extrusion of zinc showed a slight improvement of the MP reporting a YS of 45 MPa, TS of 61 MPa, and 3.8% ductility [54]. In addition, hot rolling reported the best outcome for mechanically worked pure zinc with a YS equal to 109 MPa, a TS equal to 140 MPa, and 37% ductility [55].

Table 3. Properties of Pure Zinc Alloys.

Composition	Yield Strength (MPa)	Tensile Strength, MPa	Ductility (%)	Immersion Test CR (µm/yr)	Fabrication Method	Ref.
4 N Zn	10	18	0.3	-	Casting	[53]
Zn (99.990%)	109	140	37	-	Hot rolling	[55]
Zn (99.995%)	45	61	3.8	22	Extrusion	[54]
3 N Zn	43	61	1.7	180	SLM	[56]

provides a summary of data found in previous articles covering the MP of pure zinc achieved by several fabrication methods.

3.3.2. Binary Zinc Alloys (BZA)

A binary alloy is one that consists of two components—one dominant component and one minor component, in other words, a base metal and an alloying element. The base metal, in this case, is zinc and the second element could be magnesium, aluminum, manganese, copper, tin, nickel, or any other biocompatible metal available. Many metals that are known for their good strength and ductility have been alloyed with pure zinc in hopes of enhancing its MP. The binary zinc–magnesium system (Zn–Mg) is the most explored and covered zinc alloy in the literature due to its good properties and biocompatibility [29]. The first Zn–Mg alloy fabricated for bone fixation implants was reported in 2011 by Vojtech et al. [57]. Research that was conducted at Kano University of Science and Technology explored the effect of alloying 3 wt.% Mg with Zn and the effect of metal processing techniques on the properties of the metal. Pure Zn and Mg were melted under an argon-protective atmosphere at a temperature of 550 °C. After being subjected to one pass of equal channels angular pressing (ECAP) and to two passes of ECAP, the alloy was tested as cast and homogenized at 370 °C in a vacuum environment. The TS, YS, and elongation recorded for as-cast Zn–3Mg were 84, 65, and 1.3%, respectively. The homogenized samples caused a drop in mechanical properties (TS = 46, YS = 36, and 2.1% elongation). ECAP processes, on the other hand, resulted in an improvement of MP where the best results were reported for two passes ECAP where TS, YS, and elongation were recorded to be 220, 205, and 6.3%, respectively. It was also noticed that two passes of ECAP refined the grain size of the alloy to 1.8 $\mathsf{\mu }\mathrm{m}$ while as-cast Zn–3Mg had a grain size of 48 $\mathsf{\mu }\mathrm{m}$. Owing to the refined grain size, the corrosion resistance of Zn–3Mg was improved [58]. Another promising alloying element that proven to enhance the YS and TS of zinc is copper. The binary Zn–Cu system has attracted tremendous attention in the past years [59]. Along with alloying elements, metal processing techniques have a major influence on the performance of binary zinc alloys.

Table 4. Properties of some binary zinc alloys that have been covered in the literature.

Composition	Yield Strength (MPa)	Tensile Strength, MPa	Ductility (%)	Polarization Test CR (µm/yr)	Immersion Test CR (µm/yr)	Fabrication Method	Ref.
Zn–0.5 Mg	159	297	13.0	162	81	Extrusion	[60]
Zn–3 Mg	291	399	1.0	125	76	Extrusion	[60]
Zn–3Cu	247	288	45.9	85	45	Extrusion	[61]
Zn–4Li	428	446	13.8	50	-	Hot rolling	[62]
Zn–6Li	478	569	2.4	-	-	Hot rolling	[62]
Zn–7Ag	236	287	32.0	-	84	Extrusion	[63]
Zn–0.5Al	119	203	33.0	140	79	Extrusion	[60]
Zn–0.2Mn	132	220	48.0	-	-	Extrusion	[64]

below covers a few of the findings from past published work on the topic of BZAs.

3.3.3. Ternary Zinc Alloys (TZA)

The biocompatibility of the ternary zinc system was first validated in 2011 where the composition of the fabricated alloy was 4 wt.% Al, 1 wt.% Cu and 95 wt.% Zn [57]. The alloy was made by melting the pure elements and subjecting their melt to mechanical stirring. The alloy underwent a hot extrusion process to further refine its properties. The obtained alloy through this fabrication technique was reported to have a yield strength, tensile strength, and ductility of 171 MPa, 210 MPa and 1%, respectively. Other systems like Zn–Mn–Cu, Zn–Cu–Fe and Zn–Mg–Sr have been investigated in the past, and it was claimed that they possess better mechanical properties than the Zn–Al–Cu system initially introduced [65,66,67]. Ternary alloys are more complex and less predictable than binary alloys. There are many factors contributing to the properties of designed alloys. Fabrication methods, choice of alloying elements, and concentration of metals are some of the factors that dictate whether an alloy meets the design requirement of the targeted application or not. In some cases, choosing a strengthening alloying element could significantly increase YS and TS but decrease ductility or negatively affect the corrosion rate [29]. For instance, it was discovered that adding Mg (0.1, 0.5, 1 wt.%) significantly enhance the yield strength and tensile strength of Zn–3Cu alloy, yet this increase in hardness was coupled with a severe drop in the material’s ductility [68]. Conversely, a different article reported the addition of Mg (0.1, 0.3, 0.5) to Zn–0.5Al. They concluded that the increase in Mg wt.% caused an increase in tensile strength and ductility, yet the corrosion rate of Zn–0.5Al–0.1Mg, Zn–0.5Al–0.3Mg and Zn–0.5Al–0.5Mg increased significantly [69].

Table 5. The effect of alloying elements and fabrication methods on alloys’ properties.

Alloy Composition	Yield Strength MPa	Tensile Strength MPa	Ductility %	Polarization Test CR (µm/yr)	Immersion Test CR (µm/yr)	Fabrication Method	Ref.
Zn–3Cu–0.1Mg	346	365	4.8	18	22	Extrusion	[68]
Zn–3Cu–0.5Mg	403	416	1.9	24	30	Extrusion	[68]
Zn–3Cu–1Mg	427	441	0.9	180	43	Extrusion	[68]
Zn–0.75Mn–0.40Cu	113	120	0.4	-	-	Casting	[66]
Zn–0.75Mn–0.40Cu	196	277	15.3	62	50	Hot rolling	[66]
Zn–0.35Mn–0.41Cu	77	84	0.3	-	-	Casting	[66]
Zn–0.35Mn–0.41Cu	198	292	29.6	98	65	Hot rolling	[66]

below summarizes some of the findings on the effect of fabrication methods and alloy compositions on the MP and corrosion behavior of alloys.

3.3.4. Quaternary Zinc Alloys (QZA)

Quaternary zinc alloys are the least explored among the types of alloys. This is due to the complexity of the fabrication of an alloy with more than three components including the base metal. Such complications increase production costs and lead to complex outcomes and inaccurate readings. Moreover, the field of biomaterials is still lacking deeper knowledge and a wider range of options when it comes to the less complicated alloys with fewer elements involved [29]. Among the limited data on quaternary zinc alloys in the literature, researcher Hamid Reza Bakhsheshi-Rad and his team published an article in 2017 revealing the characteristic of Zn–0.5 Al–0.5Mg–xBi (x = 0.1, 0.3, and 0.5). The study reported low tensile strengths of 102, 108, and 98 MPa for Zn–0.5Al–0.5Mg–0.1Bi, Zn–0.5Al–0.5Mg–0.3Bi, and Zn–0.5Al–0.5Mg–0.5Bi, respectively. The percent ductility this quaternary recorded ranged between 2.0–2.7%. In addition, the immersion test for this alloy reported a higher degradation rate on average than other classes of zinc alloy [70]. Until the market is saturated with binary and ternary zinc alloys and the need for quaternary zinc alloys is justified, it is reasonable to believe that exploration of QZA is unnecessary [29].

4. Biodegradable Metal Fabrication

4.1. Vacuum Melting

Metal alloy melting in a vacuum is the utilization of specialized equipment that includes a pump to evacuate air from a closed chamber achieving a low-pressure environment ideal for melting metals. This technique prevents the exposure of metal melts to air impurities, which minimizes the dissolution of unwanted gases and oxidation of metals [71]. The process of vacuum melting has been reported to ensure internal cleanliness, defect-free surface, and higher-quality alloys [72]. It also has been claimed that vacuum casting is the most environmentally-friendly process suitable for casting active elements such as magnesium [73].

An article published in 2020 studied the effect of vacuum induction melting (VIM) on the biocorrosion properties of cast magnesium alloy in comparison to sulfur hexafluoride shielding melting (USM). The corrosion resistance, surface morphology, and electrochemical properties of $\mathrm{M}{\mathrm{g}}_{67}\mathrm{Z}{\mathrm{n}}_{28}\mathrm{C}{\mathrm{a}}_5$ were closely examined for the two melting methods. All samples were melted at 750 °C and were then cast into molds. An immersion test in SBF solution revealed that VIM produced samples with superior corrosion resistance, whereas USM samples had a larger degradation rate with early signs of pitting corrosions and surface cracking. This was explained by the ununiform eutectic composition distribution and the galvanic corrosion between $\mathrm{C}{\mathrm{a}}_2\mathrm{M}{\mathrm{g}}_5\mathrm{Z}{\mathrm{n}}_{13}$ and $\mathsf{\alpha }-\mathrm{M}\mathrm{g}$ in contrast with VIM samples, which had a uniform eutectic distribution and near equilibrium cooling of the melt.

The pH change of the immersion solution was measured during the immersion test; the results show that USM samples caused a rapid increase in solution pH in the first 7–24 h after immersion, which reflects the rapid degradation of the sample at that time. On the other hand, the immersion of the VIM sample caused a gradual increase in solution pH in the first 24 h. Between 24 h and 48 h of immersion, however, the pH of the solution surrounding the VIM sample increased rapidly. Figure 3 represents a graph of the pH level change in the immersion solution for VIM and USM specimens. These changes to pH levels were attributed to hydrogen evolution coupled with the magnesium alloy degradation. The electrochemical testing of $\mathrm{M}{\mathrm{g}}_{67}\mathrm{Z}{\mathrm{n}}_{28}\mathrm{C}{\mathrm{a}}_5$ suggests that VIM produced more stable samples with a corrosion potential of −1313 mV and a corrosion current density of $1.202\times {10}^{-5} \mathrm{A} \mathrm{c}{\mathrm{m}}^{-2}$. While the USM sample reported a corrosion potential of −1483 mV and corrosion current density at $4.332\times {10}^{-5} \mathrm{A} \mathrm{c}{\mathrm{m}}^{-2}$ [74].

The main limitation of vacuum processing of metal alloys is the high cost of the necessary specialized equipment. This increase in production costs and extended set-up time is not practical for large-scale production, which requires the maintenance of the vacuum environment for longer periods [75]. To achieve the purity required of some applications, materials have to go through a double- and triple-vacuum melting process, which adds to the overall cost of production [76]. Another limitation of vacuum metal melting is the narrow range of materials that are compatible with a vacuum environment. Materials with high vapor pressure are not suitable for vacuum melting [75] given the fact that the vapor pressure of metals increases with increase in temperature [77]. Significant differences between vapor pressures of metals used could cause component volatilization, resulting in composition deviation of alloys [78]. Zn and its alloys are not compatible with vacuum protective environments for that reason [75].

4.2. Shielding Gases

Shielding gases are gases that are used to eliminate air and protect metals during casting, welding, or any other type of metal processing technique involving metals’ exposure to high temperatures [79]. The controlled atmosphere produced by the flow of the chosen gas serves an important function of minimizing impurities and oxidizing agents around metal melt hence reducing the likelihood of metal contamination and oxidation. Many gases have been studied for this purpose, and it was discovered that each gas is unique in the effect it has on the properties of the material produced and the flow of the fabrication process. Shielding gases are generally used as inert atmospheres to limit the loss of materials. However, some gases are active and are used for some specific purposes [79]. There are two types of shielding gases in terms of their chemical activity, inert and reactive [80]. More details on these types and an example of each are provided in the coming sections.

4.2.1. Argon

Argon is a noble element and one of the most frequently used gases in protective environments and gas shielding [81]. Argon gas is an example of an inert shielding gas chosen to produce the most protective atmospheres because it is more stable than oxygen and does not react with active metals under exposure to elevated temperatures. Its nonreactive nature facilitates the safe processing of reactive metal [82]. In a study that was performed at Chalmers University of Technology, the effect of argon atmosphere on the construction of 316 L stainless steel part was investigated. This study was carried out by diluting impurities such as water vapor and oxygen with a flushing technique using technical gas. The experiment was repeated using two different ${\mathrm{O}}_2$ thresholds 20 ppm and 800 ppm. The specimens were produced by laser-powder bed fusion (L-PBF) using EOS M290 equipment. The results obtained suggest that the different ${\mathrm{O}}_2$ thresholds did not affect oxygen pick up by the material and steel processing using 99.999% purity argon gas caused no change to the chemistry of the sample for both thresholds. The 316 L Stainless steel produced in this experiment under argon gas was recorded as having a relative density of 99.96 $\pm 0.02$%. SEM micrographs and EDX spectra analysis, nonetheless, reported the presence of small spherical oxide inclusions. The spherical oxide inclusions are depicted in Figure 4. EDX chemical composition analysis of these inclusions reported 44% of oxygen in the atomic makeup of the printed parts. These spheres are not severe, as is the case for processing under other gases, yet the increase in atmospheric impurities and oxygen levels reported adverse effects on the material’s resistance to degradation [82].

There has been no significant work performed to investigate the influence of argon cover gas on the fabrication of biodegradable metals (Fe, Mg, and Zn). Yet, one article studying the interaction between ultra-high purity Ar gas and pure magnesium powder disclosed that Ar inert atmosphere is only effective at a temperature of 400 °C and below. At elevated temperatures, Mg reacts with oxygen impurities in the cover gas forming magnesium oxide. The MgO formation was found to be dependent on the heating rate of the metal [83]. Another study on the influence of Ar atmosphere on the evaporation of zinc claimed that argon gas limited the evaporation of zinc due to the low diffusion rate of zinc in argon [84]. The use of Ar as a protective atmosphere has also been mentioned in various other articles emphasizing that it is a valid technique for the fabrication of biodegradable medical implants [85,86,87,88].

4.2.2. Nitrogen (N₂)

Nitrogen gas atmosphere has been used in a similar fashion to argon gas. It dilutes the impurities in the metal melting environment. However, ${\mathrm{N}}_2$ is slightly reactive and can dissolve in metal melts and form nitrides [82]. The uptake of nitrogen is favorable in some applications. For instance, the dissolution of nitrogen in steel matrix has been reported to increase steel’s resistance to pitting corrosion [89]. Furthermore, it has also been claimed that nitrogen is the most suitable densification atmosphere for the sintering of aluminum which is explained by the formation of aluminum nitride resulting from the reaction of nitrogen with aluminum [90]. For high-chromium nickel alloys, Inconel 690 alloy was determined to have the lowest porosity rate when processed under ${\mathrm{N}}_2$ atmosphere, whereas the highest porosity rates were obtained under an argon-protective environment. These results have been attributed to nitrogen’s ability to reduce the surface tension of metal melts [91]. In terms of biodegradable metal fabrication, there has been no significant body of work suggesting the use of ${\mathrm{N}}_2$ in the production of Fe, Mg, and zinc alloys.

4.2.3. Hydrogen (H₂)

Hydrogen is another active gas that is known to produce a reduction environment for metal melting, reversing any oxidation that has already occurred. Therefore, ${\mathrm{H}}_2$ gas has been used as a non-fossil reducing agent to recover oxidized metal residue after material production [92]. It has been claimed that ${\mathrm{H}}_2$ reductant works faster than any other reducing agent and achieves better results. The effectiveness of hydrogen molecules can be explained by their small size, high mobility, and low viscosity, allowing rapid diffusion [93]. Hydrogen works as a reductant by reacting with oxygen in metal oxides to produce water and pure metals [93]. The department of material science and engineering in Yonsei university conducted research investigating the kinetics of hydrogen reduction of NiO. The experiment’s parameters such as processing temperature and the nickel oxide particle size were shifted throughout the study to determine their influence on the reduction rate. It was noted during this experiment that the rate of the reduction reaction increased significantly with the increase in reduction temperature, whereas the decrease in particle size caused an increase in reaction rate. It is worthwhile to note that the experiments recorded a maximum reduction within a few minutes [94]. Hydrogen gas has been found to work similarly in reducing and recovering iron metals from its oxide [95]. Reducing iron with ${\mathrm{H}}_2$ as a reduction agent is a promising technique that could replace the excessive use of carbon as a reductive; this constitutes up to 30% of global $\mathrm{C}{\mathrm{O}}_2$ emissions. Kim et al. [96] studied the kinetics by which iron is extracted from its ore. They stated that the partial pressure of ${\mathrm{H}}_2$ contributes directly to the speed of the reducing process. Higher ${\mathrm{H}}_2$ pressure leads to a two-step reduction ($\mathrm{F}{\mathrm{e}}_2{\mathrm{O}}_3\to \mathrm{F}{\mathrm{e}}_3{\mathrm{O}}_4\to \mathrm{F}\mathrm{e}$),while otherwise a three-step reduction reaction occurs ($\mathrm{F}{\mathrm{e}}_2{\mathrm{O}}_3\to \mathrm{F}{\mathrm{e}}_3{\mathrm{O}}_4\to \mathrm{F}\mathrm{e}\mathrm{O}\to \mathrm{F}\mathrm{e}$). It was observed that the reduction of wüstite (FeO), which is the last step of the reduction reaction, consumes most of the reaction time. This was explained by the difficult diffusion of oxygen molecules through the solid form of iron formed from the reaction. Another reason explaining the slow reaction rate is the impurities present in iron (Ti, Na, Mg, and V). The reduction reaction performed was said to produce an iron structure with cracks and pores which could minorly aid the diffusion of oxygen. Based on the mentioned studies, it is safe to suggest that the addition of controlled percentages of hydrogen gas to casting atmospheres could potentially promote the production of inclusion-free, high-quality biodegradable metal alloys.

4.2.4. Carbon Dioxide (CO₂)

Carbon dioxide is an oxidizing cover gas. It makes up $\approx$0.03% of air and is usually less reactive in lower temperatures. However, it oxidizes metals and promotes the deposition of carbon at high temperatures [97]. Using gaseous $\mathrm{C}{\mathrm{O}}_2$ as a shielding gas for arc welding of metals is one of the most common applications of $\mathrm{C}{\mathrm{O}}_2$ [98]. It was claimed that pure carbon dioxide resists pore formation, yet its use imposes the risk of the carburization of materials and the formation of a higher level of spatter [99]. Furthermore, a $\mathrm{C}{\mathrm{O}}_2$ atmosphere is not suitable for thermal processes of alloys due to its oxidizing nature which result in oxidation and mass loss of alloying elements [100]. Therefore, the use of pure $\mathrm{C}{\mathrm{O}}_2$ is becoming less and less common in metallurgical techniques due to the harm that high concentrations of the gas have on the environment and human health [98]. Instead, it has been used in small percentages with other cover gases.

4.2.5. Mixed Gases

It has been observed in numerous studies that protective gas environments tend to function better with the presence of certain levels of impurities. Therefore, tremendous effort has been put into studying the behavior of various gas mixtures and the effect they have on the properties of the produced materials. For example, pure argon is not suitable for all metal processing techniques, as argon gas flow could cause bubbles and gas pockets when utilized in the process of continuous casting of steel [101]. Hence for the case of mild and low-alloyed steel, pure argon is preferred to be mixed with 5–20% of $\mathrm{C}{\mathrm{O}}_2$. It was also discovered that the addition of $\mathrm{C}{\mathrm{O}}_2$ in appropriate amounts reduces inclusions and prosody, thus producing a better quality [81]. Another advantage of utilizing Ar$-\mathrm{C}{\mathrm{O}}_2$ gas mixture for welding is the increased fluidity of the welding pool and decreased oxidation of metals. Similar effects were reported when Ar–${\mathrm{H}}_2$ gas mixture was used [79]. To the best of our knowledge, there has been no research performed on the influence of shielding gas mixtures on biodegradable implant materials. However, it was mentioned in the literature that cover gas mixtures have been employed in the casting of magnesium due to the insufficient protection of pure argon atmosphere. In Mg castings, a mixture of Ar and $\mathrm{S}{\mathrm{F}}_6$ is generally used. Nonetheless, the high global warming potential of $\mathrm{S}{\mathrm{F}}_6$ encouraged the search for alternative gas mixtures [102]. The mixture of 99% Ar gas and 0.5% of HFC 134a was proposed in 2022. This cover gas composition is claimed to provide good metal melt protection even if the gas flow is interrupted. The addition of HFC 134a to argon gas restricted magnesium ignition by forming a MgF thin protective layer on the molten and solid metal providing a smooth porosity-free surface [102].

This method of oxidation prevention is economically limiting since the pure gases used can be expensive [103]. The material processing time is also a huge factor making this method unfavorable because material processing does not start until the chamber has been cleared of air and the desired atmosphere has been reached. Thermal processing of metals under a protective atmosphere begins by the extensive flushing of impurities with inert gases or by creating a vacuum eliminating air and then flushing with an appropriate shielding gas which is performed on multiple stages. This process is repeated until the protective atmosphere has been accomplished [82]. In addition, it was reported in some papers that the closed chambers used in the process of material can commonly experience some type of air leakage fluctuating oxygen content in the atmosphere surrounding the metal melt [82]. Another significant challenge facing gas shielding methods is the adverse environmental and health impact caused by high concentrations of these gases [104].

4.3. Fluxing Agents

Fluxes are chemical elements or compounds that are added to metal melts to create a barrier restricting the interaction between oxygen in ambient air and active metals. Fluxing agents decrease metal oxidation, help remove impurities, and produce better quality materials [105]. Another function performed by fluxing compounds is lowering metal melting point and increase fluidity [106].

4.3.1. Salt Fluxing Agents

Salt fluxing treatment is an oxidation prevention and metal purifying technique using chloride or fluoride salts [105]. Fluxing salts work by binding to gases and impurities present in metal melts. The low density of these salts enables them to float to the surface of the molten metal hence increasing the purity of the alloy produced [105]. The mechanical properties and quality of alloys produced using this technique improves significantly due to the elimination of impurity and adsorbed gases. It was discovered through some studies that fluxing salt mixtures tend to work better in enhancing metal cleanliness [105].

The use of chloride salt fluxes in combination with fluoride and oxide fluxes for the protection of Mg melt was investigated in a study that was conducted in 2021 [107]. Nine unique salt flux compositions were created by mixing different weight percentages of $\mathrm{M}\mathrm{g}\mathrm{C}{\mathrm{l}}_2,\mathrm{K}\mathrm{C}\mathrm{l},\mathrm{C}\mathrm{a}\mathrm{C}{\mathrm{l}}_2,\mathrm{B}\mathrm{a}\mathrm{C}{\mathrm{l}}_2,\mathrm{N}\mathrm{a}\mathrm{C}\mathrm{l},\mathrm{M}\mathrm{n}\mathrm{C}{\mathrm{l}}_2,\mathrm{M}\mathrm{g}\mathrm{O},\mathrm{a}\mathrm{n}\mathrm{d} \mathrm{C}\mathrm{a}{\mathrm{F}}_2.$ Each salt flux serves a specific function in the flux mix. For instance, $\mathrm{C}\mathrm{a}{\mathrm{F}}_2$ was used to improve the wettability of the melt pool, $\mathrm{B}\mathrm{a}\mathrm{C}{\mathrm{l}}_2$ adjusts the melting temperature, and $\mathrm{M}\mathrm{g}\mathrm{O}$ purifies metal melt from chlorides. Specimens were prepared by covering Mg metal with a layer of salt flux mixture and this protective flux layer was removed before metal melt casting. The study concluded that most castings included small amounts of MgO, K, Ca, Na, and Mn. Yet, larger amounts of KCl and $\mathrm{M}\mathrm{g}\mathrm{C}{\mathrm{l}}_2$ limited the presence of non-metallic MgO inclusions which was observed in two of the samples. Moreover, small amounts of Mn were reported in two samples due to the increased concentration of $\mathrm{M}\mathrm{n}\mathrm{C}{\mathrm{l}}_2$. The presence of Mn in the samples reduced metal impurities, improved the corrosion resistance of the metal, and enhanced the castability of magnesium. Mass loss of magnesium metal for all specimens ranged from 6% to around 13%. Nonetheless, no significant change in mechanical properties was observed between the nine samples [107].

4.3.2. Oxidation Protection through Trace Element Addition

Microalloying with beryllium is one of the most well-established methods for oxidation protection of metal melt and it can drastically minimize oxidation and aid in the production of cleaner and high-quality alloys. The mechanism by which Be works as a fluxing agent is by forming a stable oxide layer on the surface of metal melt limiting further oxidation of alloying elements. It is crucial for the fluxing agent to be more reactive with oxygen than the metal to be cast for this step to occur. The formed BeO layer is expected to slow down the diffusion of Mg and Al through the protective layer. In past studies, the effectiveness of a beryllium fluxing agent was tested. It was determined that after a period of time, Be flux losses its function and $\mathrm{M}\mathrm{g}\mathrm{A}{\mathrm{l}}_2{\mathrm{O}}_4$, MgO, and $\mathrm{B}\mathrm{e}\mathrm{A}{\mathrm{l}}_2{\mathrm{O}}_4$ were detected in the samples [108]. Figure 5 is a representation of the working mechanism of Be flux. Previous studies have investigated the effectiveness of Be in ignition proofing of magnesium alloys. It was claimed that 0.3 wt.% of Be is capable of ignition proofing of Mg allowing melting and casting of Mg alloys with no shielding gas [109].

Adding Be trace element as a means to protect degradable Mg alloys from oxidation is an established technique that has been reported in the previous literature. In a study that was conducted at the University of Queensland, Mg–9Al–1Zn was alloyed with various compositions of beryllium to investigate the oxidation capabilities of Be [110]. The Be compositions considered for this experiment were 10, 20, 30, and 60 ppm. For each one of these Be concentrations, a specimen was fabricated and tested for oxidation resistance against Mg–9Al–1Zn alloy with no Be addition at 400 °C. It was found that the concentration of beryllium has a direct correlation to the oxidation tendency of magnesium. Larger percentages of Be were linked to a significant decrease in Mg-alloy weight gain due to oxidation. Figure 6 [110] is a visual representation of the weight gain of Mg–9Al–1Zn due to oxidation for various Be amounts. It is clear from the graph that the incorporation of 60 ppm of Be resulted in the smallest weight gain and the weight gain increased as Be amounts were reduced. Furthermore, the Mg–9Al–1Zn sample with no Be addition was the most susceptible to corrosion and was covered with loose MgO products and a 40 $\mathsf{\mu }\mathrm{m}$ thick oxide layer. The aggressive corrosion reaction formed a highly porous surface with visible cracks on the beryllium sample. Whereas, 60 ppm Mg alloy had a uniform dense surface as seen in Figure 7 [110]. It was concluded in this research that beryllium is an effective oxidation prevention method that forms a BeO layer covering magnesium melt and acts as a barrier preventing Mg exposure to oxidizing conditions [110]. The influence of the different concentrations of Be is pictured in Figure 7. These results suggest that Be can potentially be an effective fluxing agent used for magnesium melt protection.

5. Summary and Conclusions

In this literature review, we have provided an overview of biodegradable metals and alloys, as well as some pertinent applications, metal processing, and the properties of biodegradable metals and their effects on microstructures. The past literature concludes that materials’ performance is greatly affected by the concentration of alloying elements and the metal processing technique used. Although most of these studies were done under protective environments, there is a substantial lack of knowledge on the effect of the various types of oxidation prevention techniques on the properties and corrosion rate of biodegradable metallic implants. Furthermore, past studies have pointed out that the gas shielding techniques currently used in biodegradable metal alloy fabrication face major challenges and propose quality and economic challenges; additional work may be needed in this area. The field of biomaterials is in constant need of developing inexpensive biodegradable metal fabrication techniques, as the limitation of producing quality biometallic implants cost effectively and in a timely manner is still one of the most frequent issues hindering the advancement of metallic implants. Upon reviewing the previous literature, it is evident that the emergence of zinc as a biodegradable implant material holds great potential in aiding the advancement of modern medicine and addressing the limitations of previously explored biodegradable metals (iron and magnesium). To ensure the successful fabrication of adequate Zn alloy metal for the application of temporary medical implants, it is of paramount importance to choose alloying elements and fabrication techniques that enhance the mechanical properties of zinc.