Review of the corrosion behaviour in tannic-acid coated magnesium implants

Magnesium is a bio-degradable material used for bone implants because of its similar mechanical properties to bones. However, magnesium has a high corrosion rate, resulting in an implant’s degradation before the bone is fully healed. Thus, researches are conducted to study ways to improve the corrosion resistance of magnesium. Coating is one of the methods to hinder the corrosion rate of magnesium. There are two types of coatings: organic and inorganic. Organic coatings are preferable due to their non-toxicity and good biocompatibility. Tannic acid (TA) is an organic coating with a strong bond with magnesium due to its many hydroxyl groups. Besides bonding with the substrate material, tannic acid can also bind with other compounds or elements to improve the performance of the coating layer. This review evaluated several types of TA-based coatings on magnesium alloys used in orthopaedic implants and the fabrication processes affecting the structural integrity of the coating. The strategies for using TA-compound combination for corrosion mitigation with ease of fabrication process were also highlighted. This review is expected to provide some insight on the challenges and future directions of TA-based magnesium coatings for orthopaedic applications.

until the bone is wholly recovered [4].Some bone fracture cases can be healed by using external fixators, such as pins or screws, but some severe cases need an internal fixator in the form of implants [5].
Metals are the most widely used material for bone implants, where 70% are made of metals.Some commonly used metals are stainless steel, titanium alloys, and cobalt-chromium alloys (Co-Cr) [6].These materials are becoming obsolete due to their non-degradable nature, the need for a second surgery to remove them, stress shielding, and their toxicity in the body when used as implants [7].Unlike the aforementioned materials, bio-degradable metals degrade gradually, thus eliminating the need for a second surgery to remove the implant.Moreover, bio-degradable metal such as magnesium is prone to have adequate biocompatibility.For these reasons, bio-degradable metals have become the preferable choice and are still being developed for bone implants [8].
Table 1 shows that magnesium has the closest mechanical properties to human bones in terms of strength, ductility, and fracture toughness [9], allowing it to minimize the risk of stress shielding in bone implants and making it a reliable material as implants.Although magnesium is a reliable bone implant material, the corrosion rate of magnesium is faster than the rate of bone healing.Thus the implant can degrade before the bone is fully healed [10].A coating process can be carried out on the surface of magnesium to increase the corrosion resistance of the material [11].New paragraph: use this style when you need to begin a new paragraph.
Two types of coatings can be used as a coating material: organic and inorganic coatings.Several coating applications on magnesium can be seen in table 2, showing that both these types of coatings can increase the corrosion resistance of magnesium, as confirmed by an increase in the Ecorr value and a decrease in the Icorr value compared to the non-coated materials.However, compared to inorganic coatings, organic coatings are more beneficial, with significant advantages including non-toxicity and biodegradability.Organic coatings are also an environmentally green option that can be used as biocompatible coatings for biodegradable implants, such as magnesium, to provide corrosion resistance for the implants [12].a More positive Ecorr value indicates that the material is more susceptible to corrosion.b Lower Icorr value indicates that the corrosion rate is slower, and the material is more resistant to corrosion.
Catechol and its derivatives, such as Polydopamine and Tannic acid, are organic compounds that can be used as coatings as they have a high affinity for a wide variety of substrates with different surface charges [20].As polydopamine is sold at an expensive price [21], tannic acid can serve as a substitute as it has a stronger bond to magnesium due to its many hydroxyl groups [22], including eight molecules of gallic acids, a low-molecularweight derivative containing four hydroxyl groups [23][24][25].This bond, combined with its good biocompatibility and its wide availability in nature, makes tannic acid a promising option for magnesium alloy coating [23,26].The data in table 2 also shows that tannic acid is confirmed to increase the corrosion resistance of magnesium.This review discusses the use of tannic acid as coatings on magnesium orthopedic implants from the corrosion perspective.Furthermore, some analysis on the fabrication routes are discussed and current challenges and future research directions are presented.

Tannic acid
Tannic acid is a polyphenol compound with a high molecular weight with the empirical formula of C 76 H 52 O 46 [12].The molecular structure of tannic acid can be seen in figure 1.The hydroxyl group enables tannic acid to be attached as an organic-based coating.The data in table 2 shows that tannic acid-based coating is confirmed to increase the corrosion resistance of magnesium.Accordingly, tannic acid is quite promising in corrosion mitigation for metal-based orthopedic implants, especially bio-degradable magnesium-based implants.
2.1.The use of tannic acid in bone fracture healing Tannic acid has been used in bone fracture healing as it has good biocompatibility and has been shown to promote the growth of connective tissue [20,27].Research conducted by Sahiner et al (2016) shows that tannic acid has proteins, especially collagen fibrils (as seen in figure 2, known as cell regeneration's accelerator [29]. Tannic acid also has antioxidative and antibacterial properties, especially gram-positive bacteria [31,32].This antibacterial feature is essential as bacterial infections are among the most common and dreaded postsurgery complications [33].This case of infection is also the type of infection that frequently occurs where a study conducted by Maathuis et al (2005) shows a 30% chance of bacterial infection among 60 hip replacement surgery patients [34].
Equally important, the antioxidative feature serves as an additional defense mechanism of the body since there is an increase in free radical production while a fracture is healing [35].Moreover, tannic acid is antiinflammatory [24,35].These features make tannic acid one of the remarkable compounds in bone fracture healing.

Tannic acid as implant coating
The hydroxyl group in tannic acid has a vital role in forming bonds between tannic acid and other elements [28].Like other polyphenols, tannic acid can form chelation bonds with metal ions [30,35,36].Many hydroxyl  groups on tannic acid facilitate efficient three-dimensionally stabilized metal-phenolic networks (MPNs) [36].The ability to form MPNs is why tannic acid is often used as coatings on metal-based orthopedic implants to improve the corrosion resistance of the metals [12].Similarly, the antioxidative, antibacterial, and antiinflammatory properties mentioned in the previous section also support the ability oftannic acid to be used as coatings in non-metal-based implants.Table 3 displays some applications of tannic acid on implants.

Magnesium implant
Pure magnesium bone implants were first used in 1900 as bone pins and bone plate forms.In the following years, the application of magnesium implants was continuously developed, resulting in the fabrication of the implants in various forms, such as bone screws, bone pins, and bone plates [41].However, the use of pure magnesium as bone implants was overlooked due to its rapid corrosion rate [42].Thus, research and development of magnesium implants were continuously performed to control the degradation rate [8].In 1938, magnesium implants in alloy forms began to be used to heal bone fracture patients [41].This alloying process was carried out to improve the mechanical properties and corrosion resistance of magnesium.

Magnesium implant degradation
Magnesium, including one that has undergone an alloying process, can completely degrade in the human body, so magnesium implants only serve as a temporary support to hinder misalignment during the bone healing process [20,21].The resulting degradation products do not show any toxicity because magnesium is one of the most abundant compounds in human bodies [22,27].The approximate magnesium content in the human body is 25 grams, with a maximum daily intake of 0.7 grams/day [43].In the blood, the magnesium content is 900 μmol/L, while the magnesium content in the bones is 1.7 mg g −1 [44].
Despite the non-toxicity of the degradation product, high corrosion rate, apart from wear, is one of the limitations of magnesium as a bone implant material, as a low corrosion rate is required in bone implants to maintain its mechanical strength [41].This high level of corrosivity is due to the chemical properties of magnesium with the standard electrode potential of −2.37 [45].The chemical reactions that occur in the magnesium corrosion process can be seen in equations (1)-( 4) [46].
Mg(OH) 2 is a passive film product that can improve the corrosion resistance of magnesium alloys [9].In corrosive media with a chloride content of above 30 mmol L −1 , Mg(OH) 2 will react to form MgCl 2 [47], which will then determine the corrosion rate of the magnesium alloy [48].
Pitting corrosion is a common mode of corrosion occurring in more than 93.5% of magnesium bone implants [49].The presence of impurities such as Fe, Ni, and Cu can accelerate the rate of pitting corrosion [50], and these impurities are cathodic to magnesium with a very negative corrosion potential [51].The allowable corrosion rate of bone-implant material is the same as the bone repair rate within the range of 0.2-0.5 mm year −1 [52].

Tannic acid as magnesium-based implant coating
Although magnesium has gone through an alloying process, a coating process can further raise the corrosion resistance of magnesium [41].With many hydroxyl groups and antioxidant, antibacterial, and antiinflammatory properties, tannic acid is one of the highest potential compounds for magnesium coating.Tannic acid and magnesium can bind to form metal phenolic networks (MPNs) [12].A study conducted by Chen et al (2008) showed that the bond formed between tannic acid and magnesium was a Penta-hydroxy benzamidemagnesium complex.This MPNs layer prevents magnesium from directly interacting with the environment to increase its corrosion resistance [12].
The MPN formation between TA and Mg begins by converting TA into GA through hydrolysis under acidic conditions [39].Then, gallic acid oxidizes to Penta-hydroxybenzoic acid, and finally, Penta-hydroxy benzoic acid binds to Mg and forms a complex bond [28].
Several studies show an increase in corrosion resistance in magnesium alloy coated with tannic acid characterized by an increase in Ecorr and a decrease in Icorr.Data on changes in Ecorr and Icorr can be seen in table 4.
In table 4, the changes on Ecorr and Icorr are calculated by comparing the Ecorr and Icorr of the coated materials with the corresponding uncoated material.It can be seen that Tannic Acid/Poly N-vinylpyrrolidone (PVPON) 5 has the most significant increase in Ecorr (83,607%) and decrease in Icorr (−92,931%).Poly (Nvinylpyrrolidone) (PVPON) is a widely-used polymer as a binder in pharmaceutical tablets.The coating is done in layer-by-layer (LbL) assembly for drug delivery [54], as this type of assembly can degrade gradually due to the reversible dynamic hydrogen bond between PVPON and tannic acid [55].The degradation of tannic acid coating on magnesium alloys, processed by an alternate immersing process between tannic acid and PVPON, also happens gradually, slowing down the coating's degradation rate.
-Homogenous coating structure -Thin (<500 nm) -pH = 4 -Fast process at room temperature Immersion time: 5 min TA/PVPON 3  Mg 70 Zn 26 Ca 4 0.25 mg/ml C 76 H 52 O 46 and 0.25 mg ml -Uniform coating structure -Requires many chemicals The tannic acid coating process on magnesium alloys can be done using the immersion method.The process begins with gradual grinding of the substrate material using SiC sandpaper up to 2000 grit to create a uniform surface.Subsequently, the substrate is cleaned with 10% sodium hydroxide for 15 min at a temperature of 60 °C-70 °C [28].Lastly, the rinsing process is carried out using deionized water or ultrasonically using 70% ethanol for 4 min before finally rinsed with distilled water [38].
After the pre-treatment process is completed, the coating process continues by immersing the substrate in a tannic acid solution at various pH and temperature conditions for a specific time.Tannic acid can also be blended with additives to minimize TA-Mg pores [54].Some of the solutions used in the coating process can be seen in table 5.
As seen from table 5, the frequently used solution compositions for coating processes on magnesium are Na 3 PO 4 , Na 2 B 7 O 4 , C 76 H 52 O 46 , NH 4 VO 3 , K 2 ZrF 6 , and HNO 3 , which are used in AZ91, AZ31, and AZ91D coating process.The presence of HNO 3 aims to maintain the pH level at 4, which is mandatory in a process with this composition [28].This composition can be carried out at room temperature, which is more favorable, or at 37 °C, as in TA-AZ31 and TA/HA-AZ31.This process can also be continued with other processing, such as the addition of HA (increasing the thickness and density of the coating) or Ni-P (increasing the corrosion resistance of the tannic acid coating layer) [16,53].The coating process with this method can be carried out in varying intervals ranging from a few minutes to several hours to obtain various thicknesses.However, one disadvantage of this method is the large number of chemicals required for the coating process.
Another method that can be used is the anodic coating used in the TA-AZ91 coating process, utilizing simpler chemicals.However, the coating layer formed is not uniform if the composition used is only NaOH and tannic acid.In comparison, the addition of Na 2 SiO 3 .9H 2 O to the solution results in a uniform and thick coating layer.However, this method requires an electric current and a cooling system during the coating process [53].
The tannic acid coating layer can be further enhanced by adding certain chemicals as a coating compound.The combination of TA and HA increases biocompatibility, coating thickness, and density but requires many chemical materials, long processing time, heating elements, and a non-uniform and porous coating structure.In comparison, TA/Ni-P coating can further enhance the corrosion resistance of the coating layer, but the coating process is gradual and requires many chemical materials.
The TA/PVPON has some advantages regarding the fabrication process: it takes place at room temperature, it has a relatively neutral pH, and the required solutions only need three primary materials: tannic acid, PVPON, and PBS (phosphate buffer saline).This coating process can produce a thin uniform multilayer coating by immersing the specimen alternately in those two solutions with PBS rinsing in-between immersions [54].One immersion cycle will produce one layer of the coating.

Challenges and future research direction
Tannic acid coating on magnesium effectively increases biocompatibility and corrosion resistance.However, more significant improvements are possibly achieved by coatings from tannic acid combined with other chemical compounds, such as TA/PVPON, TA/HA, and TA/Ni-P.However, most of the TA-based coating processes resulted in cracks or pores appearing in the formed layer after long-term use (as seen in table 5).
Cracks that appeared in the coating layer are caused by capillary stresses arising from the evaporation of entrapped water in the coating that widens with the thickening of coating layers [38].These cracks can spread and damage the coating layer, which can also trigger pitting corrosion.Thus, forming holes in the material, causing both stress concentrations or microcracks formation, potentially leads to a material failure [56].It is clear that extensive studies on the process of TA-based coating to enhance structural integrity need to be conducted.Similarly, further research regarding the long-term use of TA coating in bone implants as well as the occurring pitting corrosion also needs to be carried out to ensure its efficacy.

Conclusion
Magnesium is one of the best bone implant materials with a relatively high corrosion rate, which requires a coating process to improve corrosion resistance.As a tissue-growth-promotor organic coating, tannic acid is an alternative corrosion-resistance-enhancer magnesium coating with a hydroxyl group that boosts the affinity of tannic acid with magnesium.However, tannic acid needs to be bound with other elements or compounds to improve the coating performance.The combination of TA and HA increases biocompatibility, coating thickness and density but requires many chemical materials, long processing time, heating element, and a non-uniform and porous coating structure.Overall, there is a significant prospect for tannic acid and its compound coatings to contribute both to the development of surface modification for biodegradable magnesium alloys and the solution of the profound issues associated with magnesium-based implants.
Nevertheless, even though the works reviewed herein on TA-based coatings have led to the improvement of magnesium-based implant performance, most of the TA-based coating processes result in some structural imperfections that can cause unpredictable failure.Thus, it is evident that more alternative routes of coating processes and modification still need to be explored further.

Figure 2 .
Figure2.Possible hydrogen bonds in collagen and tannic acid crosslink adapted from.Reprinted from[30], Copyright (Year), with permission from Elsevier.

Table 2 .
Ecorr and Icorr value of uncoated and coated magnesium.

Table 3 .
Application of tannic acid on implants.Scaffold TA binds to PHPE b by hydrogen bonding with the help of the crosslink agent NaIO 4 .PHPE-TA showed good compatibility and osteoconductivity.

Table 4 .
Ecorr and Icorr value of various magnesium alloys.
a More positive Ecorr value indicates that the material is more susceptible to corrosion.b Lower Icorr value indicates that the corrosion rate is slower, and the material is more resistant to corrosion.