Magnesium is one of the most required nutritional metallic elements required by human body for multiple health benefits. Its non-toxicity makes it a potential non-permanent implant material in human body. However, magnesium is also one of the most susceptible elements to wet corrosion. Its reaction with simulated bio fluids leads to localized increase in magnesium ions, pH, formation of hydrogen bubbles and formation of Ca-P layer. In view of corrosion susceptibility and its effects on the neighboring environment, the potential of Mg-based materials as implants is presented in brevity keeping the interest of a broad spectrum of researchers in mind.

Metallic materials are commonly used as permanent and non-permanent implants in human body for more than a century.^1,2 This stems from their ability to exhibit good strength, ductility and fracture toughness which holistically remain beyond the capabilities of polymers and ceramics. For permanent implant applications such as knee and hip replacements, we need the materials to be inert means targeting the ones with minimum or extremely low corrosion rates and high wear resistance. Moreover, the corrosion products have to be non-toxic and the metal ions/debris that is generated should also lead to appropriate host response. Titanium and steels are commonly used as implant materials for such purposes. Titanium is more stable in body but is expensive while steels are cheaper but remains comparatively more reactive when compared to titanium. Co-Cr alloys were also attempted but led to adverse host response and acute toxicity and are being currently avoided by research community.^3–5 A list of commonly used metallic materials as implants is shown in Table 1.⁶

Magnesium is the lightest and one of the most abundant metallic materials with a density (1.74g/cc) and elastic modulus (40-45GPa) closest to bone.^1,16 This translates to almost no stress shielding effect. The compressive and tensile strengths of magnesium and its alloys can easily be tailored to exceed that of bone and its ductility in both compression and tension remains higher than bone making it a mechanically suitable material for implant applications. Human body needs about 250-400mg of magnesium per day as magnesium is the fourth most prevalent ion in human body and assists in bone health, multiple metabolic processes in body and exhibit antibacterial properties against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.¹⁷ As magnesium is biocompatible and biodegradable, its use as non-permanent biodegradable implant in human body ensures:

1. No revision surgery.
2. Reduced patient trauma.
3. Reduced medical cost.
4. Reduced doctor’s time.

Moreover, excess magnesium can easily be excreted through urine thus preventing any side effects that may arise due to excess magnesium.

As magnesium is currently targeted as biodegradable implant, it is important to understand its corrosion behavior as the degradation of magnesium-based implants has to be controlled and tuned with the bone healing time such as in orthopedic applications. Moreover, an understanding of the impact of dissolution on the surrounding tissues has to be clear. The corrosion of magnesium in aqueous medium can be expressed as:

Anodic Reaction: $Mg\to M{g}^{2+}+2e^{-}$

Cathodic Reaction: $2H_{2}O+2e^{-}\to 2O{H}^{-}+H_2$

Investigating these equations reveal that following will happen locally as a result of corrosion of magnesium implant in the body:

1. Increase in Mg ion concentration.
2. Increase in pH.
3. H₂ bubble Formation.
4. Formation of Ca-P layer.

The effects of each of these events are described in Figure 1.

Figure 1 Beneficial effects of corrosion of magnesium in bio-applications.

The positive effects of magnesium ion concentration are described in.^18,19 The positive effects of pH increase are reported in.²⁰ The benefits of hydrogen formation are indicated in.²¹ Finally, the Ca-P layer that is formed on magnesium implant and its positive effects are reported in reference 18 based on in vivo studies. Overall, it can be seen that magnesium corrosion in human body is beneficial provided its rate can be controlled to avoid undue surges. More study is also required to establish the upper limit of pH that can be tolerated by human tissues. A list of metallic ions in the body is presented in Table 2. The information indicates that magnesium and iron are two possible choices as implant materials which are a significant part of human body systems. Trace elements can be used as alloying elements only and not as main elements as they can lead to toxicity as observed in the case of Co-Cr implants.

Magnesium based compositional systems that have been investigated in recent past for bio-applications are listed in Table 3.¹ More details on these systems can be found from.¹ The alloys/composites shown in Table 3 exhibit different properties and corrosion rates. Accordingly, they can be used as implants depending on healing time required by body to heal an injury which is not a constant and depends on the age of individual and type of fracture. For example, while certain fractures can heal in 3 weeks in young kids, it may take 6 weeks to heal in teens. In addition, based on the type of bone fractured (e.g. tibia or phalanges) the average healing time may vary from 3-12 weeks.²² The required lifetime thus has to be based on worst case scenario which is about 12 weeks. In yet another research finding, researchers in Kobe University, Japan developed Mg-based surgical clips that can be exit the body in about a year. Monitoring was done for about 12 weeks suggesting yet again that typical healing period is benchmarked at 12 weeks for most the cases.²³

In-vitro and in-vivo studies correspond to the studies conducted outside and inside body environment. In-vitro studies are less expensive and are used to qualify/shortlist the potential materials for implant applications. In-vivo studies are conducted in humans or animals and at times challenges the research ethics. However, as long as the intention of researchers is to bring comfort and to improve the quality of life of patients the rule utilitarian and duty ethics are satisfied. Researchers are always attempting to correlate in-vitro results with in-vivo results so as to speed up the qualification time of implants. It may be noted that as the complexity of living system cannot be duplicated in in-vitro studies, not all the time the results can be correlated. Targeting magnesium, the fundamental differences in in-vitro and in-vivo studies are indicated in Table 4.²⁴

Besides the differences in the two types of studies, some research work also showed similar outcome of the two types of studies.²⁵ For example, researchers reported the ability of Ca-P layer generated on magnesium implant to promote tissue growth during biodegradation in both in-vitro and in-vivo.^26,27 In yet another study, investigators indicated that in-vitro tests can be translated to in-vivo behavior provided a proper test bed is created and due considerations are given to simulate the actual conditions and function of implant in the body.²⁸

The main challenge faced by researchers in their pursuit to use magnesium based implants is to control their corrosion/degradation rate within the human body. This requires a well planned in-vitro testing followed by in-vivo testing. The main variables in-vivo that may have complex interactions and can significantly affect the corrosion rate is:²⁸

1. Location of implant.
2. Stress levels on implant.

For example, stresses can trigger stress corrosion cracking and corrosion fatigue and if they are not targeted in in-vitro testing than the results of in-vitro testing will be misleading. Additionally, there are still unknowns in the use of larger implants in animals/humans in terms of how much pH rise and increase in magnesium ion concentrations locally can be tolerated by the surrounding tissues. Further research is warranted in this area.

Magnesium based materials have emerged as potential biomaterials and both animal and human studies have been conducted successfully on patented/protected compositions. Choice of magnesium based materials as biomaterials is still limited for materials selectors and its portfolio needs significant enhancement to go from smaller implants (pins, clips and screws) to larger implants (such as plates) and as scaffolds. The key challenge is to control the degradation rate at different levels depending on the function of implant and its required lifetime in human body. Further, it has to be ensured by material scientists that the inherent composition of the implant does not release ions or corrosion products that can create local or systemic toxicity. As the magnesium based implants avoids the revision surgery and comes with related benefits, advancement in this area has the potential to create a multi-billion dollar market with noble cause of alleviating human discomfort.

None.

The author declares no conflict of interest.

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