Advances in hydroxyapatite coatings on biodegradable magnesium and its alloys

Ai-Meng Zhng, Prneesh Lenin, Rong-Chng Zeng,c,∗, M.Boy Knnn

a College of Materials Science and Engineering, Shandong University of Science and Technology, Qingdao 266590, China

b School of Mechanical Engineering, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India

c School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450002, China

d School of Engineering, University of Newcastle, Callaghan, New South Wales 2308, Australia

Abstract

Keywords: Hydroxyapatite; Magnesium; Biomaterials; Biodegradation; Coating.

1.Introduction

Non-degradable implants made of metallic materials, e.g.,titanium alloys and stainless steels, are commonly used for the repair of bone fractures [1–3].Indeed, there are potential complications with these materials due to metal reactions and inflammation when they undergo wear/degradation [4].In the aim of substituting these non-degradable materials, a great deal of research work has been done on biodegradable biomaterials.Various biodegradable polymers, including polylactide, polyglycolide, polycaprolactone and chitosan have been researched for biomedical applications [5–8].The major issue with these polymers is their poor mechanical strength, which limited their applications only to low load-bearing implants[9].

Magnesium, a lightweight metal, has favorable physical and mechanical properties for load-bearing implant applications [10–13].Due to its excellent biodegradability in physiological environment, magnesium is considered for use as a biodegradable implant material [14–17].In aqueous media,magnesium undergoes oxidation and forms magnesium hydroxide.However,in the presence of chloride and near neutral pH, the film is dissolved i.e., magnesium hydroxide converts to soluble magnesium chloride, as shown in the following reaction:

Hence, the main concern of using magnesium as a biodegradable implant material is that its degradation in body fluid is too high [18,19].This can lead to a decrease in the structural integrity of the implant during service.The unacceptably high degradation rate of magnesium and its alloy leads to a higher rate of hydrogen evolution.The hydrogen evolution rate of pure magnesium is as high as 10 mL/h or 40 mL/(cm2·d), while the allowable degree of hydrogen absorption by the human body is only 2.25 mL/(cm2·d) [20].When magnesium degrades, a large amount of hydroxyl ions(OH-) will be produced, which consequently increase the pH of the microenvironment surrounding the implant and could potentially cause harm to the growth of human bones and tissues.Further,it should be noted that magnesium is susceptible to localized degradation [21]which increases the possibility for magnesium implant failure.

Over the past few years, alloying has been done to magnesium, and their biodegradation tendency has been evaluated.Those magnesium alloys primarily include AZ (aluminum,zinc) series, calcium-containing and rare-earth containing alloys [22–27].The general degradation rate has been reduced by alloying, but the alloys are susceptible to localized degradation [28,29].

Surface coatings largely reduce the localized degradation or at least delay the localized attack of magnesium-based materials.Several coating methods including ceramic coatings and polymer coatings are available for application on magnesium and its alloys [30–35].There are a few review articles on various coating processes, including HAp coatings,on magnesium-based materials [36–41].In fact, one of the authors of this article has written a book chapter on HAp coatings on magnesium and its alloys [42].However, this review article serves as an update, particularly focusing on the recent advancements in the HAp coating methods on magnesium and its alloys for improved biodegradation resistance and biocompatibility.

2.Hydroxyapatite and coating techniques

Hydroxyapatite (HAp) is a bioceramic material(Ca10(PO4)6(OH)2), which has hexagonal crystal structure, as shown in Fig.1 [43].The lattice parameters are:a=b= 0.943 nm,c= 0.688 nm, the angle between the a and b axes are 120°, and the unit cell contains 10 Ca2+, 6 PO43-tetrahedra, and 2 OH-.The atomic ratio of Ca/P is 1.67, which is the main component of natural bones.It has excellent bioactivity and osteoconductivity,which can quickly integrate with the bones and promote the growth of new bones.Hence, it is widely used in artificial bones, teeth, joints, and other artificial implant products.Currently, it is considered as an important material in the field of biomaterials and also has huge development potential[44–46].

Fig.1.Crystal structure of HAp [43].

The most widely used application of HAp is in coating of metal implants.The metal-ceramic composite combination can not only exert the excellent bioactivity and osteoconductivity of HAp but also use the metal matrix to ensure the overall mechanical strength of the implant.There has been a large amount of research work on HAp coating on metal implant materials such as stainless steels and titanium alloys [47–50].Various coating techniques are available, including chemical[51], hydrothermal [52], electrochemical deposition [53],plasma spray [54], ion implantation [55], sputtering [56]and sol-gel methods [57].Since some of these methods operate at high temperatures, it is extremely challenging to deposit HAp on magnesium-based materials.However, chemical and electrochemical coating methods are attractive for coating HAp since they are done at relatively low temperatures and are also not expensive and is feasible to coat intricate shaped implants[58,59].A broad classification of HAp coating methods on magnesium-based materials is illustrated in Fig.2.These methods are described in detail in the following sections.

2.1.Chemical and hydrothermal conversion

Chemical and hydrothermal conversion are commonly used in the preparation of HAp coatings on magnesium alloys[37].Table 1 summarizes the various HAp coatings on magnesium and its alloys through chemical and hydrothermal conversion.

Table 1A list of various HAp coatings on magnesium and its alloys by chemical and hydrothermal conversion.

Chemical conversion coatings result from the complex interaction of metal dissolution and precipitation, and are usually obtained by immersion in an aqueous solution at room or slightly high temperatures.Magnesium alloys easily degrade and the difference in electrochemical potential between the matrix and secondary phase particles in the alloy provides the driving force for forming the conversion coating.The chemical conversion of CaP coating can be carried out at room temperature, mainly in an acidic calcium phosphate solution, with high interface bonding strength and density,which is beneficial to improve the degradation resistance of medical magnesium alloys [60–62].Hiromoto and Yamamoto[63]showed that HAp can be formed directly on magnesiumbased materials in an aqueous solution containing Ca-EDTA(C10H12N2O8Na2Ca).It was reported that the Ca-chelate compound maintains a high concentration of Ca2+ion at thesurface of magnesium and as a result promoted HAp formation.The HAp-coated samples exhibited higher resistance to degradation as compared to bare metal in NaCl solution.

Fig.2.A broad classification of HAp coating methods on magnesium-based materials.

Zaludin et al [64].fabricated calcium phosphates (CaP)coating on magnesium using chemical conversion method.Interestingly,they found that post-alkaline treatment of CaP significantly deteriorated the degradation resistance as compared to the untreated CaP coated magnesium (untreated corrosion current density:25.2 μA/cm2and post-alkali treated corrosion current density: 120.9 μA/cm2).In fact, the porosity in the untreated CaP coating(0.3%)was lower than the post-alkaline treated coating (27.6%).The same group [74]coated HAp on magnesium via two-step chemical conversion i.e., phosphating and then alkaline treatment and studied its degradation behavior.They observed that the HAp coating performance was affected by the ionic concentrations of the degradation testing solution i.e., degradation current increased in the following order:Ring’ers(676.8 μA)>SBF(236.0 μA)>PBS(11.1 μA).

Recently, Nago et al [65].formed HAp and octa calcium phosphate(OCP-Ca8H2(PO4)6·5H2O)with and without monetite (CaHPO4) layers on AZ31 Mg alloy using chemical solution deposition method at various pH values (5.5–8.6).The HAp coating formed in pH 7.5 was found to be denser and exhibited higher adhesion strength (6.7 MPa) as compared to that formed in pH 8.6 (3.8 MPa).However, theOCP coating in pH 5.5 and 6.2 exhibited higher adhesion strength (4.2 MPa).They reported that the coating adhesion strength decreased (20–30%) with immersion in Eagle’s minimum essential medium (E-MEM).On the other hand, Braga et al [66].fabricated dicalcium phosphate dihydrate (DCPDCaHPO4·2H2O) coating on magnesium matrix by a chemical method.The coating (14 μm thickness) formed on the sample after immersion in phosphate bath for 24 h provided the highest polarization resistance (Rpof 16 × 103Ω·cm2).

Fig.3.Formation mechanism of HMDTMPA/HAp film formation via 1-step and 2-step methods [67].

Soliman et al [67].used two methods, i.e., single solution(one-step) and two different solutions (two-step), to prepare hexamethylene diamine tetrakis methylene phosphonic acid(HMDTMPA)/HAp hybrid coating.The HMDTMPA/HAp hybrid coating prepared by the two-step method exhibited improved degradation resistance due to the formation of less soluble dense DCPD phase; while the one-step method the coating formed a soluble and loosely packed monocalcium phosphate monohydrate (MCPM) phase.The mechanism of degradation and formation of both the coatings are illustrated in Fig.3.

Highly crystallized HAp was coated on magnesium using a single-step hydrothermal treatment by Hiromoto and Tomozawa [68].They used Ca-EDTA with various pH levels for the HAp coating.It should be noted that the solubility of the highly crystalline HAp is lower than that of the amorphous HAp.It was reported that the pH influenced the morphology of the coating, i.e., plate-like crystals at 6.3 pH, needle-like at 7.3 pH, and rod-like crystals at 11.3 pH.The authors observed that the HAp coatings increased the degradation resistance of magnesium in SBF by over an order of magnitude.Hydrothermal treatment condition influences the initial protectiveness of the coating.Interestingly, 4-day immersion in SBF covered the defects in the coatings via HAp formation.The same group [69]reported that the development of the HAp crystals was improved with increase in temperature.This was be due to the dissolution of magnesium, since its dissolution enhances with an increase in the electrolyte temperature.It was also observed that the hydrothermal treatment temperature influenced the shape of HAp crystals and growth direction.Recently, Ali et al [70].deposited CaP (monetite) on a magnesium alloy using hydrothermal deposition.The high strength monetite was highly crystalline and cytocompatible.The deposition done at 100 °C exhibited compact and defects free coating.Lap shear test showed that the cohesive failure was at 21.89 MPa.Further, the degradation rate in SBF was 80% lower with the coating as compared to the bare metal.

The combination of the hydrothermal method and other technologies has shown that it can further improve the degradation resistance of HAp coated magnesium and its alloys.Li et al [71].pre-deformed ZEK100 magnesium alloy with a high-pressure torsion (HPT) and then coated HAp with Mg(OH)2nano powder by hydrothermal method.The HPT process refined the grain size and introduced twins in the alloy, which enhanced its microhardness and Young’s modulus.Apparently, the fine grains, twins and grain boundaries provided more nucleation sites for HAp crystals and thus produced a dense and thick HAp coating with fine crystal size.Further, it was reported that the coating reduced the degradation rate of the alloy in PBS.Another group [72]prepared HAp coating via micro-arc oxidation(MAO)of magnesium inan electrolyte with different concentrations of trisodium phosphate (Na3PO4) and subsequent hydrothermal treated in calcium nitrate (Ca(NO3)2) solution.They found that the phosphor content in the MAO coating influenced the morphology of HAp i.e., 12.1 wt.% phosphor content exhibited nano-flake morphology and 20 wt.% phosphor content showed nanoparticle morphology.The nano-flake coating exhibited higher degradation resistance and cytocompatibility as compared to nano-particle coating.

Fig.4.Preparation route of PMTMS/HAp coating on magnesium alloy [73].

There are studies on the application of silane on HAp coatings on the surface of magnesium alloy.Zhao et al [73].prepared polymethyltrimethoxysilane (PMTMS)/HAp hybrid coating on AZ31 magnesium alloy via hydrothermal treatment and immersion method.The coating preparation method is shown in Fig.4.Since HAp and silane possess excellent chemical and physical properties, the combination of HAp and silane significantly improved the degradation resistance.

Tomozawa and Hiromoto [75]studied the mechanism of HAp coating on magnesium.They found that a dome-shaped HAp precipitates formed on the sample which resulted in a dual-layer coating.The coating contained an inner dense layer of HAp and an outer coarse layer containing rod-like HAp.In another study, the same authors [76]coated HAp with and without OCP on pure Mg using Ca-EDTA solution.A dual-layer structure was formed when the treatment electrolyte was weakly acidic.Microscopy analysis showed that the dual layer consisted of a coarse outer layer (exhibiting plate-like OCP crystals) and a dense inner layer (HAp crystals).In a weak alkaline electrolyte, the dual layer consisted of a coarse outer layer with rod-like HAp crystals and a dense inner layer with HAp crystals.In another study, Hiromoto and Tomozawa [77]reported that the effectiveness of the HAp coating towards degradation protection hinges on the inner layer and not on the type of magnesium material, which was based on the study on HAp coated magnesium and AZ31 magnesium alloy tested in 3.5 wt.% NaCl electrolyte.

A two-step chemical method was used to prepare HAp coating on AZ60 magnesium alloy by Su et al [78]..First,a phosphating process was used to produce DCPD coating,and then an alkali heat treatment was performed to convert DCPD to HAp.They found that the HAp coating remarkably lowered the degradation rate of the alloy in NaCl and SBF electrolytes.The mechanism involved in the HAp coating on a magnesium alloy was studied by Gray-Munro et al [79]..It was suggested that the nucleation and growth of HAp on the alloy surface were catalyzed via anodic dissolution.The coating formed was calcium magnesium HAp,which was less crystalline.They proposed the following mechanism:

Overall,considering the production cost and environmental friendliness, the method of chemical treatment and hydrothermal conversion is beneficial for the formation of HAp coating.At the same time, it also has a disadvantage, i.e., formation of uneven and thin coating.

2.2.Biomimetic method

Biomimetic method of coating is a special process that simulates natural CaP biomineralization that is carried out at temperatures and pH values closer to physiological conditions [80].Usually, a longer immersion time is required to accelerate the nucleation of apatite on the metal substrate.As compared with other coating technologies, it has many advantages such as lower deposition temperature and also provides good coverage of samples with complex geometries that cannot be achieved using traditional methods [81].At present,biomimetic technology has been primarily studied to prepare CaP coatings on magnesium substrates [82].

Zhang et al [83].coated HAp on pure Mg using a biomimetic method.They reported that the dual-layer coating was more efficient in reducing the degradation resistance as compared to that of the single-layer coating.Lu et al [84].developed a Ca-deficient HAp coating on ZK60 magnesium alloy via a biomimetic technique in SBF solution (pH 5–7 and Ca/P 1.67).The coating exhibited ball-like shaped particles with Ca/P of 0.86–1.24.The coating formed in pH 6 SBF exhibited the highest degradation resistance and biocompatibility.

Recently, Zhu et al [85].used sol-gel spin coating method and biomimetic mineralization to produce an aminated hydroxyethyl cellulose (AHEC)-induced HAp biomimetic coating on AZ31 magnesium alloy.It is found that HAp/AHEC coating significantly improved the degradation resistance of the alloy in SBF.

However, the lack of nucleation sites for HAp growth in magnesium alloys makes it difficult to form.Thus, the future work should focus on the combination of the biomimetic method and other coating methods.

2.3.Electrochemical deposition

Electrochemical deposition method has been widely used in engineering and biomedical fields [58].The preparation process usually uses a three-electrode system, i.e., the sample is used as the working electrode (sample), reference electrode and counter electrode (platinum/graphite).The advantages of the electrochemical deposition method are that the thickness of the formed coating can be controlled, the coating purity is high and the coating process is relatively simple.Basically,the deposition parameters such as current/voltage and electrolyte need to be controlled for achieving the desired coating thickness and morphology.In recent years, a significant amount of work has been done to optimize the deposition parameters of CaP coatings [86].

Song et al [87].deposited HAp on AZ91D magnesium alloy via an electrochemical method.The coating formed contained DCPD andβ-tricalcium phosphate (β-TCP,Ca3(PO4)2), and when the coating was soaked in 1 M NaOH solution for 2 h, the coating turns into HAp.The HAp coating reduced the degradation of AZ91D magnesium alloy in SBF.Using the same method, Wen et al [88].prepared HAp coating on AZ31 magnesium alloy.The coating transformed to nano whiskers of HAp under alkali treatment.James et al[89].conducted a similar study on the HAp coating on pure magnesium, and the study indicated that its degradation resistance was increased by three-fold.

Guan et al[90].proposed a three-step HAp coating method on Mg-4.0Zn-1.0Ca-0.6Zr (wt.%) alloy.The coating method consisted of an alkali pretreatment followed by electrodeposition and then alkali post-treatment.The hemolysis rate of the HAp coated sample was less than 5%.The HAp-coated alloy exhibited a slightly higher growth rate of fibroblasts as compared to the uncoated samples.

Hydrogen evolution in the conventional coating techniques such as constant-potential and constant-current is a major issue which affects the coating on the material.However,pulseelectrodeposition technique can potentially decrease the hydrogen evolution rate during the coating process [91].This technique was used by Wang et al [92].to coat HAp with a Ca/P ratio of 1.33 on an Mg-Zn-Ca alloy.The HAp coating decreased the degradation rate of the alloy, and it was also found that by adjusting pulse width and amplitude, the coating shows better adhesion Fig.5.shows micro-CT 2D reconstructed images of magnesium implants with and without Cadeficient HAp coating.The implantation period was from 8 to 24 weeks.At 8 weeks, the external modality and structure of the bare magnesium implant show degradation pits (Fig.5a),while the surface pits of the Ca-deficient HAp coating alloy were minimal (Fig.5e).As the implantation time increases,the degradation of the coated sample became gradually severe(similar to the bare sample) owing to the partial failure of the coating (Fig.5c,d,g,h).Kannan and Wallipa [93]also utilized the pulse-deposition technique to deposit CaP on AZ91 magnesium alloy.The pulse-potential coating showed that the polarization resistance of the pulse-potential coating was ～3 times higher than that of the constant-potential coating in SBF.

Thein vivodegradation behavior and bone response of pulse-deposited HAp on Mg-Zn-Ca alloy were studied by Wang et al [94].It was noticed that thein vivosurvival of the coating was ～8 weeks, thereafter the coating showed deterioration.A novel approach, i.e., adding ethanol to the coating electrolyte, was used by Kannan [95]to minimize the hydrogen bubbles during the coating process.The coating formed with ethanol-containing electrolyte exhibited densely packed particles.The degradation resistance provided by the coating formed in ethanol-containing solution was superior to the conventional coating.Kannan [96]also assessed the synergistic effect of pulse-method and ethanol inclusion in the coating electrolyte on the coating formation.The coating formed by the combination of the two methods was superior to the coating developed by only the pulse method because of the tightly packed morphology of the coating particles.The sameapproach was used by Kannan et al [97].to electrochemically coat CaP on Mg-Ca alloy and studied its degradation behavior and cytocompatibility.They found that the entire alloy surface was covered with flat and irregularly oriented CaP particles,and the coating thickness was 5 μm.The cytocompatibility test shows that the coating improved the cytocompatibility of the alloy and effectively inhibits the release of Mg2+ions.The degradation study showed that the coated alloy significantly improved the degradation resistance.

Fig.5.Micro-CT 2D reconstructed images of magnesium containing implants with and without Ca-deficient HAp coating with implantation period of 8–24 weeks [92].

Recently,Udin et al[98].prepared HAp coating on AZ31B magnesium alloy by the electrodeposition method.They reported that the coating produced using 3 mA/cm2current density resulted in a compact, dense and uniform coating as compared to the coating formed at 6 and 13 mA/cm2current densities.As a result, they observed that the coating done at low current density (3 mA/cm2) exhibited the lowest degradation rate (1.56 mm/y).The electrodeposition process for preparing HA coating is shown in Fig.6.Tayyaba et al [99].coated HAp on Mg-Zn-Zr alloy using electrophoretic deposition method.The 15 μm thick HAp coating reduced the degradation rate by more than 5 times in Ringer’s solution.They also noticed nano-sized Mg(OH)2needles growth on the coating.

Electrophoretic deposition (EPD) is a colloidal method in which charged particles in suspension undergo electrophoresis to achieve dense surface film deposition on an oppositely charged working electrode [100].Brunton et al [101].prepared a 15 μm-thick dense HAp coating on ZK60 alloy by electrophoretic deposition technology and studied its degradation behavior over time.The coating reduced the degradation rate of ZK60 alloy in Ringer’s solution by 5 times.However,the HAp coating showed signs of deterioration after 72 h of soaking, and it was completely dissolved within 128 h.Saadati et al [102].used three different voltages (50, 100, and 150 V)to carry out electrophoretic deposition of HAp coating on the surface of Mg-4Zn-4Sn-0.6Ca-0.5Mn alloy.The study found that at 150 V and deposition time of 5 and 10 s a crackfree coating with the best bonding strength was formed.When the coating thickness was greater than 70 μm, voids were evident, and micro-cracks appeared when the coating thickness was greater than 100 μm.

Fig.6.Schematic diagram of electrodeposition process for preparing HA coating [85].

In summary, electrochemical deposition is a low-cost and a simple process.The thickness and chemical composition of the HAp coating can also be tailored by adjusting the electrodeposition conditions.However, the deposition process is usually accompanied by the generation of hydrogen bubbles which affect the quality of coating.Pulse electrodeposition technique and changing the electrolyte composition haveshown to reduce the generation of hydrogen bubbles and produced better coating.

2.4.Radio frequency method

Radio frequency(RF)magnetron sputtering is a high-speed vacuum coating technology, which belongs to the category of physical vapor deposition.This method is used to deposit thin films with a thickness in the range of 0.04–3.5 μm on the surface of metal materials [103,104].It has advantages such as good bonding strength, high efficiency, and controllable performance [105,106].Hence, this technique has gained attention for HAp coating on magnesium-based materials.Surmenva et al [107].used an RF magnetron sputter deposition method to coat HAp on AZ91 magnesium alloy and then investigated the adhesion of bone marrow stromal cells (BMSCs) andin vitrodegradation behavior of the coated samples.The RF coating was done at a substrate bias of -25 and-100 V and followed by annealing.The authors found that the coating at -100 V reduced the release of magnesium ions and showed higher BMSCs adhesion density as compared to the sample coated at -25 V.Interestingly, Yadav et al [108].claimed that the hydrophilic AZ31 magnesium alloy turned hydrophobic after RF sputtering of HAp.As a result, compared with bare alloy,the degradation rate of 9 h coating alloy in SBF is reduced by 20%.Achenson et al [109].formed CaP coating on AZ31 magnesium alloy via RF magnetron sputtering from HAp powder targets.They obtained two coating thicknesses of CaP, i.e., ～70 and 210 nm Fig.7.shows the ToF-SIMS depth profiles of CaP coated AZ31 Mg alloy and the ToF-SIMS positive polarity ion mapping.Based on μCT analysis of the 14 days exposure of the samples to SBF,the authors reported that CaP coating decreases the degradation rate and higher thickness exhibited higher resistance to degradation (Bare metal: 1.74 mm/year; ～70 nm CaP coated:1.57 mm/year; ～210 nm CaP coated: 1.01 mm/year).

2.5.Laser and ultrasonic methods

Advanced techniques such as laser and ultrasonics have been applied for improving the properties of HAp coating on magnesium alloys.Laser surface engineering is a material processing method, where the heating and cooling rates are fast, and thus the laser technique provides favorable thermodynamic conditions for the coating preparation [110].Due to the difference in the melting point of magnesium alloy and hydroxyapatite, a good metallurgical combination of the coating can be achieved by laser technology [111].Kalakuntala et al [111].produced laser patterned HAp coatings on AZ31 magnesium alloy Fig.8.shows the laser processing method of forming HAp coating on AZ31B magnesium alloy and the change of laser trajectory.The coating with lower contact angle (<60°) showed higher degree of biomineralization and better degradation protection in the 5 days immersion in SBF.

Currently, ultrasonic technology is widely used in the synthesis of HAp powder,which can provide a high driving force for the growth of HAp crystals [112].In addition, ultrasound can promote the dispersion of HAp, and thereby is considered suitable for achieving a good interface bonding between the coating and the substrate.The use of ultrasonic-assisted technology to synthesize HAp coating on magnesium alloys can coating provide better bonding strength between the coating and the alloy [113].Sun et al [113].studied the effect of ultrasonic time on the properties of HAp coating on AZ31 magnesium alloy.A dense and crack-free HAp coating with interface boding strength of 18.1 MPa was reported.The coating produced under 1 h ultrasonication provided good protection against degradation in the SBF immersion tests for 90 days (bare metal: 175.2 μA/cm2; coated: 5.56 μA/cm2).

Although, there are a few applied researches works on these two advanced methods, the influence of laser intensity and ultrasound time on the coating formation should be further explored.

3.Functional composite coating

3.1.Substituted hydroxyapatite coating

In recent years, substituted HAp coatings (doped with fluorine, zinc and strontium) have gained high interest for better biodegradation properties and bioactivity.The influence of different substitutes in HAp coating on magnesium alloy is listed in Table 2.Yang et al [114].studied the biodegradation and mineralization activity of HAp-coated,DCPD-coated,and fluoridated HAp (FHAp)-coated magnesium-zinc alloy in SBF.Their authors found that all the coatings (electrochemically deposited) reduced the degradation of the alloy.The deposits on the uncoated and DCPD-coated alloy exhibited a low Ca/P molar ratio.Both FHAp and HAp coatings promoted nucleation of bone-like apatite orβ-TCP.They also reported that the HAp coating was less stable and fragile, so its long-term resistance to degradation was not high.They noticed that FHAp was relatively more stable and exhibited higher resistance to degradation.Li et al [115].also studied FHAp coating on magnesium-zinc alloy.They found that the cell viability was higher after a week in comparison against the normal culture case (negative control).In vivoimplantation of the coated sample exhibited relatively lower degradation, and after a month of implantation period a better interface contact was observed.

Table 2Influence of different substitutes on HAp coating on magnesium-based materials.

To overcome the hydrogen evolution during the coating of FHAp on a magnesium-based material, Meng et al [116].utilized pulse electrodeposition technique and H2O2in the electrolyte.A uniformly dense nano-FHAp coating was formed.Jiang et al [117].compared the degradation influence of alkali (NaOH) and acid (HF) treated CaP coatings on AZ31 magnesium alloy in SBF.They reported that HF treated coating composed of compact chrysanthemum-like fluorine-doped HAp exhibited excellent degradation resistance.The coating provided more than 10 weeks of protection, keeping the degradation rate below 0.5 mm/year.Yu et al [118].prepared fluoridated HAp/MAO composite coating on AZ31B magnesium alloy.They found that the thickness of the FHAp/MAO coating was 20 μm and it showed good adhesion.The degra-dation resistance was also higher in FHAp/MAO as compare to CaP/MAO coating (AZ31B: 132 μA/cm2; MAO coated:10.6 μA/cm2; FHAp/MAO: 0.38 μA/cm2).

Fig.7.ToF-SIMS depth profiles of: (a) AZ31 Mg alloy with ～70 nm CaP coating and, (b) AZ31 Mg alloy with ～210 nm CaP coating, and (c) ToF-SIMS positive polarity ion mapping of AZ31 Mg alloy with ～210 nm CaP coating [109].

Fig.8.The laser processing method of forming HAp coating on AZ31B magnesium alloy and the change of laser trajectory [111].

Recently, Li et al [119].prepared Ca-deficient HAp/MgF2bi-layer coating on high purity magnesium through fluoride and hydrothermal treatments.They reported that the coating with nanoscale surface topography exhibited good adhesion strength (14.94 MPa) and improved degradation resistance in SBF (bare: 331 μA/cm2; coated: 2.24 μA/cm2).Further, the proliferation of MG63 cells increased with the bi-layer coating as compare to single layer HAp and MgF2coatings.

Wang et al [120].developed a biodegradable Zn-modified CaP coating on Mg-Zn-Ca alloy using dual pulse electrodeposition.The introduction of Zn changed the formation mechanism of the coating.Electrochemical analysis showed that the Zn-modified CaP coating improved the anti-degradation performance of the alloy and exhibited a better protective effect than the ordinary CaP coating.Ibrahim et al [121].studied the influence of aging temperature and zinc content on thein-vitrodegradation properties of heat-treated and CaP deposited Mg-Zn-Ca alloy.They found that 1.2 wt.% Zn content aged at 200 °C showed the lowest degradation rate and CaP coating (via MAO) further reduced the degradation rate.After 8 weeks exposure in SBF, the total mass loss of the coated sample was only 1.52%, and the compressive ultimate strength reduced by 11.3% and the ductility reduced from 18.1 to 16.2%.

In addition to alloying, doping of these biocompatible elements is gaining high interest in medical applications, especially in coatings.Zhou et al [122].developed zinc-doped nanowhisker HAp coating on ZK60 magnesium alloy via hydrothermal method.They observed that zinc doping changed the morphology of HAp to nanowhisker.The nanowhisker zinc-doped (5 wt.%) HAp coating improved the degradation resistance of the alloy and exhibited good biocompatibility i.e., promoted adhesion and differentiation of rate bone marrow mesenchymal stem cells and inhibits bacteria, as compared to the conventional HAp coating.A Zn-HAp/Zn doublelayer coating was developed by Yao et al [123].on AZ91D magnesium alloy via cold spray method.The authors reported that the zinc powder was plastically deformed and partially oxidized due to its low melting point, whereas HAp powder was fragmented.

Iquab et al [124].coated zinc-doped HApzeolite/polycaprolactone composite coating on magnesium using dip-coating technique.The coating with thickness of ～226–260 μm coating exhibited high degradation resistance(bare: 95.59 μA/cm2and coated: 10.32 μA/cm2).The zincdoped coating also exhibited antimicrobial activity against E.coli.Zhou et al [128].used a hydrothermal method to prepare nano-HAp/ZnO coatings on Mg-Zn-Ca bulk metallic glass.Thein vitroantibacterial rate of magnesium -based bulk metallic glass was close to 100% due to the presence of ZnO in the coating.The coating reduced the degradation current density of the alloy from 113.24 to 12.35 μA/cm2.

Similar to zinc-doping, strontium-doped HAp coatings on magnesium alloys have also been done.Wang et al [125].coated strontium-doped nanorod/nanowire HAp on ZK60 magnesium alloy.The strontium addition changed the shape of HAp from nanorods to nanowires and the coating morphology from flower-like to network structure.Further, it has enhanced the degradation resistance.The degradation current of ZK60 was 146 μA/cm2and HAp coating reduced it to 5.09 μA/cm2and strontium-doped HAp further reducedto 1.6 μA/cm2.Also, Makkar et al [126].studied the effect of strontium-doped CaP coating on a magnesium alloy.The coating with ～20 μm thickness reduced the degradation and improve biocompatibility.After 14 days exposure in Hank’s solution, the weight loss without coating was 17.2%and with coating was reduced to 4.8%.They reported that after 4 weeks of implantation in the rabbit model, the bone formation around the coating was higher and the osseointegration was better (Fig.9).

Fig.9.Histological analysis of magnesium alloy and Ca-Sr-P coating 2 and 4 weeks after implantation using multiple staining solutions [126].

Wei et al [127].synthesized Sr-HAp nanocrystals via a hydrothermal method.A new type of functional surface modification on AZ31 magnesium alloy was done via self-polymerization of dopamine and coupling of Sr-HAp nanocrystals, carboxymethyl chitosan, and alendronate(ALN), which is a specific drug for treating osteoporosis, coassembled in the polydopamine (PDA) coating.This coating slows the degradation rate of magnesium alloys and also slows the release of Sr-HAp nanocrystals and ALN.

A number of techniques have been introduced, as stated above, to improve the performance of HAp coatings by substituting key trace elements.At the same time, the morphology and microstructure of substituted HAp coatings will also change and thereby promoting bone formation and improving cell activity.Future research should focus onin vitroandin vivostudies on these coatings to determine the appropriate degree of substitution for each element.

3.2.Medicine-loaded and bioinspired hydroxyapatite coating

Loading useful medicine that could release slowly or incorporating bioinspired compounds in the coating is certainly an added advantage for implants.Due to the lack of nucleation sites on polished magnesium-based materials, it is difficult to perform a direct biomimetic deposition of HAp.To solve this issue, organic additives have been applied to induce and stimulate the formation of HAp [129].Ji et al [130].prepared a multilayer coating with HAp and ciprofloxacin (CIP)-loaded polymer on AZ31 magnesium alloy by the combination of hydrothermal treatment and layer-by-layer assembly.CIP molecules with carboxylate groups can promote the formation of dense HAp coatings.They reported that the multilayer coating exhibited favorable degradation resistance in SBF (bare: 134 μA/cm2; HAp coated: 9.44 μA/cm2; multilayer coating: 1.59 μA/cm2).As expected, the multilayer coating exhibited excellent antibacterial activity and cell compatibility.In another study, the same group [131]developed a coating with HAp and gentamicin (GC)-loaded polymer on AZ31 magnesium alloy.Polyacrylic acid is a water-soluble polymer with a high binding capacity.The interaction between-COO- and Ca2+ions helped the formation of the coating.The multilayer hybrid coating not only enhanced the biocompatibility but also improved the degradation resistance of the alloy while delivering the vital drug.The degradation current density of the HAp-GC coated alloy was 0.85 μA/cm2,which was slightly better than HAp-CIP coated alloy(1.59 μA/cm2).

Liu et al [132].developed DNA-induced CaP coating on an extruded magnesium alloy via hydrothermal deposition.The presence of DNA improved the conglutinate strength of the coating by 18% and also the degradation resistance of the alloy increased in Hank’s solution (degradation current density-DNA free: 6.2 μA/cm2; DNA-induced:2.1 μA/cm2).Recently, Cui et al [133].prepared a chitosan (CHI)/deoxyribonucleic acid (DNA) multilayer film(CHI/DNA)5/Mg(OH)2on AZ31 magnesium alloy pretreated with NaOH.The composite coating has a dual function, i.e.,the inner layer Mg(OH)2coating played the part of the physical barrier, and the outer layer (CHI/DNA)5coating induced the formation of a HAp protective layer during immersion.The results showed that the degradation current density of the composite coating reduced by about two-order of magnitude.The CHI makes the coating exhibit good antibacterial properties Fig.10.shows the degradation mechanism and an-tibacterial of (CHI/DNA)5/Mg(OH)2coating.Fan et al [134]..coated L-cysteine-bioinspired CaP on AZ31 magnesium alloy in a 60 °C water bath.The nucleation process of the coating was promoted by L-cysteine and increased the thickness of the coating from 9.67 μm to 18.67 μm.As a result, it was found that the degradation current of the coating with L-cysteine(0.42 μA/cm2) was significantly lower than the controlledcondition coating (7.21 μA/cm2) in Hank’s solution.

Fig.10.Schematic representation of the degradation mechanism and antibacterial activity of (CHI/DNA)5/Mg(OH)2 coating [133].

Zhao et al [135].successfully constructed gentamicin sulfate (GS) loaded polyelectrolytes multilayers (PEMs) on a magnesium alloy via the spin-assisted layer-by-layer assembly and heat treatment process.After the heat treatment, carbonyl groups on different poly acrylic acid (PAA) molecules were cross-linked by heating to form stable anhydride bonds.The degradation current density of the heat-treated coating is an order of magnitude lower than that of the untreated coating,which indicates that it has good degradation resistance due to the cross-linking.In addition, the heat-treated multilayer coating promoted the formation of HAp after being immersed in SBF for a longer period.

It is clearly evident that loading antibiotics in HAp coatings is one of the most effective ways to alleviate the problem of implant infection.Different organic molecules induce the formation of HAp and also improve the degradation resistance of the alloy, which is dual action.

3.3.Hydroxyapatite composite coating

HAp composites, mixture of HAp and other elements/compounds, are known for their excellent mechanical properties.A metal matrix composite with HAp particles and AZ91 magnesium alloy was prepared by Witte et al [136].The mechanical properties of the composite were tailored by changing the particle size and distribution of the HAp particles.Interestingly, HAp particles controlled the degradation rate in cell solutions and artificial sea water.Gu et al [137].developed Mg/HAp (10, 20, and 30 wt.%) composites using a powder metallurgy method.They found that 10 wt.% of HAp exhibited uniform distribution, whereas 20 wt.% HAp had a few HAp clusters and in 30 wt.% HAp agglomeration was seen.The yield strength of the composite (Mg/10HAp)increased as compared to that of as-extruded magnesium.However, with the further increase of HAp content, the yield strength, ultimate tensile strength, and ductility of Mg/HAp composites decreased.The authors noticed that the degradation rate of Mg/HAp composites increased with the increase in HAp content, and the Mg/10HAp exhibited no toxicity to L-929 cells; however, the Mg/20HAp and Mg/30HAp composites decreased the cell viability.

The common PEO, also known as micro-arc oxidation(MAO), technique has been studied for developing HAp composite coatings on magnesium-based materials [138].Wang et al [139].prepared a MAO coating containing HAp on pure magnesium through adding HAp particles to a Ca-P-based electrolyte.HAp particles improved the degradation resistance of the coating as a result of the increased compactness of the coating.Sreekanth and Rameshbabu [140]formed a composite coating of MgO/HAp on AZ31 magnesium alloy via electrophoretic deposition (EPD) and plasma electrolytic oxidation(PEO)techniques.They reported that the MgO/HAp coating substantially increased the degradation resistance in SBFat pH 4.5 and 7.5.Tang et al[141].developed HAp coating on AZ31 magnesium alloy via a PEO method.The PEO coating also increased the degradation resistance of the alloy.When the electrolyte contained Ca-EDTA + potassium dihydrogen phosphate(KH2PO4),the micro-pores and micro-cracks in the PEO coating were sealed by creating a barrier layer and thus the degradation of the alloy was largely lowered as compared to the PEO coating alone.Kannan et al [142].developed a PEO–CaP coating on magnesium via plasma electrolytic oxidation (PEO) and electrochemical deposition methods.The PEO–CaP coating enhanced the biocompatibility and reduced the degradation of magnesium.The degradation current density of composite coated magnesium is significantly better than bare magnesium and PEO coated magnesium, which was about 99% and 97% lower, respectively.Recently, Han et al [143].deposited CaP on magnesium alloy PEO coating using cathodic electrodeposition method.The authors reported that the CaP coating (DCPD + HAp) exhibited excellent degradation resistance in the 3 months immersion in SBF (Fig.11).

Fig.11.Long-term electrochemical degradation behavior of CaP-PEO coated magnesium at 37 ± 0.5 ºC in SBF [143].

Researchers have also incorporated HAP in polymers and then coated on magnesium alloys.Zhou et al [144].coated polydopamine intermediate layer-induced HAp on an extruded AZ31 magnesium alloy using a hydrothermal treatment.The dopamine-induced HAp coating was found to be more compact as compare to pure HAp coating and thereby increased the degradation resistance significantly in SBF (degradation current - bare metal: 381 μA/cm2; coated: 2.47 μA/cm2).Also, they reported that the composite coating exhibited good proliferation, spread of osteoblasts, and adhesion.Guo et al [145].coated polydopamine/dicalcium phosphate dihydrate/collagen composite on AZ60 magnesium alloy via a two-step chemical method.They reported that the multilayer coating greatly enhanced the degradation resistance in SBF (degradation current - bare metal: 27 μA/cm2; coated:0.17 μA/cm2).This composite coating was also found to improve the cytocompatibility and osteogenic differentiation ability.Cui et al [146].developed layer-by-layer assembled polyacrylic acid (PAA) multilayers induced CaP coating on AZ31 magnesium alloy.Both hydrogen evolution and electrochemical degradation testing methods showed improvement in the degradation protection of the alloy in Hank’s solution.Zhang et al [147].formed a polycaprolactone (PCL)/HAp composite coating on AZ31 magnesium alloy.Compared with a single HAp coating, the bonding strength of PCL/HA coating on the alloy was significantly higher,and the electrochemical degradation rate reduced by 10 times.

Incorporation of carbon nanotubes (CNTs) or graphene in biomaterials for achieving higher mechanical properties is gaining interest in recent years.Khazeni et al [148].developed a HAp-CNT composite coating on AZ31 magnesium alloy via cathodic electrodeposition.The pulse-deposited HAp coating containing 1 wt.% CNTs exhibited high crystallinity(71.2%) along with a uniform structure.It was reported that due to addition of CNT the elastic modulus and hardness increased by 42% and 130%, respectively, as compared to the pure HAP coating.In a subsequent study, the same group[148]reported that HAp-CNT composite coating reduced the degradation current density of the alloy in SBF from 44.25 μA/cm2to 0.72 μA/cm2.Further, they noticed formation of new layer of HAp on the alloy surface after 5 days immersion in SBF.

Wu et al [149].developed a reduced graphene oxide (rGO)reinforced apatite composite layer on AZ31 magnesium alloy via one-step hydrothermal treatment.The apatite layer was composed of CaHPO4and HAp with prismatic shaped grains.The coating reduced the degradation current by an order of magnitude in SBF (bare metal: 104 μA/cm2; apatite coated: 98.1 μA/cm2; rGO-Apatite coated: 33.5 μA/cm2).Peng et al [150].coated HAp-graphene oxide bilayer on AZ31 magnesium alloy.It was found that graphene oxide inhibits the formation and growth of degradation crack on HAp layer and thereby exhibited higher degradation resistance(degradation current - bare metal: 22.4 μA/cm2; HAp coated:2.37 μA/cm2; HAp-graphene oxide coated: 1.50 μA/cm2).The authors concluded from theirin vitrocell viability tests that the coating has superior cell proliferation rate.

Recently, Kannan et al [151].developed a triple-layered hybrid coating (PEO–CaP-PLLA).The top poly (L-lactide acid) PLLA layer contained self-organized micropores.The triple-layered hybrid coating reduced the degradation current density of pure magnesium from 28.79 μA/cm2to 0.24 μA/cm2, which is highly significant.Yu et al [152].prepared Fluoride/Polydopamine/Sulphonated hyaluronic acid(MgF2/PDA/S-HA) composite coating on ZE21B magnesium alloy.The results revealed that the composite coating not only inherits the anticoagulant effect of sulfonic acid groups and excellent cytocompatibility of S-HA but also significantly increased the degradation resistance of the alloy.It can be considered that the structure of the three-layer coating has great potential in controlling the degradation rate of magnesium alloy implants.

Currently, modification of HAp multifunctional composite coating on the surface of magnesium-based materialsis a research hotspot.As compared with HAp-only coating, the composite coatings have shown to improve the degradation resistance and biocompatibility of the substrate material.However, there is a lack ofin vivoresearch work and therefore for successful application of such coatings furtherin vivoresearch is needed.

4.Mechanical integrity of coated implants

The localized degradation tendency of magnesium-based materials could potentially affect their mechanical integrity during service [153,154].Typically, the localized attacked region can be the point of stress concentrators and lead the material to fracture under loading conditions.It is well known that magnesium-based materials are susceptible to stressassisted failure [155–157].Due to the significant amount of chloride ions in body fluids, magnesium and its alloys are easily undergo localized degradation in the body, and its mechanical integrity could be affected [158,159].HAp coating has the potential to delay the onset of localized degradation in magnesium and its alloys.

Fig.12.Schematic representation of Mg/β-TCP and HAp coating on Mg-Zn-Y-Nd alloy [162].

A pulse electrodeposition method was used by Wang et al[160].to develop a Ca-deficient HAp coating,which is soluble with a Ca/P ratio of 1.33, on a Mg-Zn-Ca alloy.The mechanical integrity of the coating was evaluated using slow strain rate testing (SSRT) technique.The authors reported that the ultimate tensile strength (UTS) and time of fracture (ToF) of the Ca-deficient HAp coated alloy was higher than that of the uncoated alloy.A different approach was used by Wang et al[161].to evaluate thein vitromechanical integrity of HAp coated AZ91 magnesium alloy.They exposed the HAp coated alloy to SBF for 5 days and then the mechanical properties were analyzed.They reported that the HAp coating improved in thein vitromechanical strength by 20% in comparison with the uncoated alloy.High localized attack was observed in the uncoated alloy, whereas the attack was minimal in the HAp coated alloy.

Zhang et al [162].used friction stir processing (FSP) to disperse tricalcium phosphate (β-TCP) particles in Mg-2Zn-0.46y-0.5Nd alloy to prepare magnesium-based functionally graded material (Mg/β-TCP FGM).The HAp coating was prepared on the surface of Mg/β-TCP FGM via electrodeposition.The schematic representation of Mg/β-TCP and HAp coating on Mg-Zn-Y-Nd is shown in Fig.12.Theβ-TCP with FSP layer not only plays the role of refining grains but also helps to improve the bonding strength.The study demonstrated that after four FSP treatments, Mg/β-TCP exhibited a uniform fine-grained microstructure and the microhardness increased from 47.9 HV to 76.3 HV.As compared with samples withoutβ-TCP, the binding strength of the Mg/β-TCP FGM slightly improved from 23.1 ± 0.462 to 26.3 ± 0.526 MPa due to the reduction in the thermal expansion coefficient between the substrate and the coating.

Li et al [163].used PEO and hydrothermal treatment to form a bilayer-layer structure coating (termed as HAT) on the magnesium surface.The HAT-coated magnesium promoted mineralization of bone sialoprotein and osteopontin secretion, forming a cement line matrix.The cement thread matrix wraps each HAp nanorod,fills the gap between the rods of the HAT coating, forms a strong interlocking at the bone-coating interface, and enhances osseointegration through contact osteogenesis.As compared with PEO coatings and bare magnesium, magnesium HAT coating maintains the mechanical integrity for a longer period.

5.Summary and future perspectives

Hydroxyapatite (HAp) coatings are highly efficient in controlling the degradation rate of magnesium-based materials and delaying the onset of localized degradation.This is important for load-bearing orthopedic implant applications.Over the last decade, numerous researchers have worked on HAp coatings on magnesium and its alloys using chemical, hydrothermal and electrochemical deposition methods.Recently,other techniques such as radio frequency, laser and ultrasonic methods have been explored for that purpose.The recent focus has been on substituted, medicine-loaded and composite HAp coatings for enhanced degradation resistance and biocompatibility of magnesium-based materials.However, more work is needed to assess the mechanical integrity performance of the newly developed HAp coatings for successful applications.

Composite HAp coatings have great prospects for controlling the degradation rate and enhancing the mechanical integrity of magnesium and its alloys.Moreover, the composite HAp coatings can enable the magnesium and its alloys to have the necessary biological functions, such as facilitate tissue regeneration,antibacterial properties,biocompatibility and drug release capability.Hence,it can be said that the development of magnesium alloy along with composite HAp coating could be an effective way to improve the biological functions of magnesium alloy implants in addition to providing the required degradation resistance.

In future research work, to better simulate the performance of these advanced coatings in the physiological environment,it is critical to establish anin vitroenvironment similar to the human physiological conditions for evaluating their degradation.Although a large number ofin vitrodegradation experiments on magnesium-based materials have been carried out over the past decade, the fact is that most of them were done in simple environments such a chloride-containing solution and in room temperature.It is critical that by only clarifying the actual degradation mechanisms of the coated magnesium materials in the body, we can provide vital l guidelines for the design and development of novel high-performance,multifunctional HAp coatings for magnesium-based materials.

Acknowledgement

This work was supported by National Natural Science Foundation of China (Grant No.52071191) and Open Foundation of Hubei Key Laboratory of Advanced Technology for Automotive Components (No.XDQCKF2021006).