SOJ Materials Science & Engineering

Magnesium and its alloys are researched widely for their use in biodegradable temporary implant applications. However, higher rate of degradation and hydrogen gas evolution limits the use of magnesium-based materials as temporary implants. Till date, various modifications like addition of alloying elements, processing conditions, surface modification and coatings are done to overcome these drawbacks. Another way to circumvent these limitations is to add reinforcement to magnesium and its alloys. Magnesium-based composites, as biomaterials, can exhibit excellent mechanical and microstructural properties like ultimate tensile strength, ultimate compressive strength, elastic modulus, grain refinement and corrosion resistance in the physiological conditions. Accordingly, this paper targets to investigate the influence of addition of different types of reinforcements to magnesium and it alloys on their microstructural, mechanical and corrosion responses.
Keywords: Magnesium; Metal matrix composites; Corrosion; Biomaterial; Temporary Implants

Metallic materials used in temporary fixation procedures in the form of stents, screws, nails and bone plates need good degradation properties, corrosion resistance, mechanical integrity and should be biocompatible to the human tissues [1]. Various metallic materials like titanium alloys, stainless steel and cobaltchromium- molybdenum (Co-Cr-Mo) alloys are used extensively in various biomedical applications [2-5]. These materials exhibit superior load bearing capacities and corrosion resistance; however, they have various pitfalls like high elastic modulus leading to stress shielding effects, non-biodegradability, and most often than not, their fixation procedures require secondary surgery for the removal of these materials from the body owing to their non-biodegradable nature [2, 6-11]. Additionally, the stress shielding effects caused by these materials lead to change in the loading pattern on the implants causing screw loosening and hinders new bone formation [8]. In an ideal scenario, a material should naturally resorb into the human body over the time after the bone healing process is completed without creating local or systemic toxicity. Magnesium is one such bioresorbable metal having functional properties like elastic modulus (40–45 GPa) and density (1.738 g/cc) closely matching that of the natural bone (~15–30 GPa, 1.1-1.3 g/cc) thereby avoiding the stress shielding effects and eliminating the need for second surgical intervention [12]. Additionally, magnesium is osteoconductive and thereby facilitates bone cell growth and has also been shown to contribute to cell attachment [13]. However, the major limitation of magnesium is its poor corrosion resistance in physiological environments [14, 15]. Due to fast degradation rate, magnesium implants lose their mechanical integrity and lack the ability to stay inside the tissue until the new bone formation has occurred [16]. Alloying, composite and/or coating technology can be effectively used to alleviate these concerns. Alloying Mg with biocompatible elements like Zn, Ca, Si, amongst others can improve the corrosion resistance and biocompatibility [17- 19]. Further, coating magnesium substrates with bioceramics or fluorides is also known to enhance the functional properties of magnesium [20-22]. However, many of these processes are expensive and their inability to tailor the specific properties could be a potential concern. Another way to enhance the performance of magnesium-based materials in physiological environment is through the judicious addition of low-cost low-volume secondary reinforcements. Such reinforcements in magnesiumbased matrices can provide a suitable alternative to enhance the corrosion resistance and biocompatibility of magnesium. The addition of nanoscale particle to the magnesium is known to increase its mechanical integrity and decreases the corrosion rate. Literature shows that various nanoparticles like alumina (Al2O3) [23], zirconia (ZrO2), yttria (Y2O3) [10], graphene nanoplatelets (GNPs) [67], calcium phosphate ceramics (CPCs) [24-26] when in magnesium-based matrices can improve the mechanical properties and reduce the corrosion rate. Accordingly, the main aim of this short review is to focus on various reinforcements that can be added to magnesium and it alloys to influence their mechanical and corrosion responses to suit for biomedical applications.

Titanium Based Reinforcements
Titanium is a bioactive material widely used for the manufacture of orthopaedic and dental implants, and is a preferred reinforcement to improve bioactivity of composite materials owing to its high mechanical strength, excellent fatigue and tensile strength, chemical inertness, superior corrosion resistance, wear resistance, biocompatibility, low modulus of elasticity, good hardness and most importantly comes at low cost [27-33]. Similarly, titanium-based ceramics have also been used in multiple bio-applications qualifying them to be used a reinforcement [28]. Bordji et al. developed magnesium-based composites using Titanium dioxide (TiO₂) particles reinforcement (45 μm) in various amounts (4 wt. %, 8 wt. %, 12 wt. %, 16 wt. %, and 20 wt. %) using powder metallurgy technique [27]. By increasing the amount from 4 wt. %, to 20 wt. % the microhardness increased from 37 HV to 50 HV. Similarly, the ultimate compressive strength (UCS) increased up to 330 MPa for 20 wt. % TiO₂ reinforcement containing composite.Aydin et al. demonstrated that addition of TiB2particulates (40 μm) to magnesium matrix in the amount of 10, 20 and 30 wt.%, increased the hardness of the matrix to 65 HV for 30 wt.%, when compared to that of pure Mg of 40 HV [34]. Titanium dioxide (TiO₂) nanoparticulates (∼21 nm) reinforced magnesium matrix composite was synthesised using powder metallurgy technique coupled with hot extrusion by Meenashisundaram et al.[29]. The addition of (TiO₂) with different amounts (1.5, 2.5 and 5 wt. %) showed a 21% decrease in grain size. The grain size of pure Mg was 34 μm. With increasing the amount of TiO₂ from 1.5% to 5%, grain size decreased from 32 to 27 μm. Well-defined grain boundaries and grain boundary pinning effect was reported by investigators [35]. Mg reinforced with 0.58, 0.97, 1.98 and 2.5 vol. % titanium nitride (TiN) nano particulates of ~20 nm size were successfully synthesized by disintegrated melt deposition (DMD) technique followed by hot extrusion by Meenashisundaram et al. [30]. Addition of TiN reinforcement progressively reduced the grain size with 2.5 vol. % reinforcement addition showing the minimum grain size accounting to 57 % reduction (Table 1)[36]. Meenashisundaram et al. synthesised Mg–Ti nanocomposites using DMD followed by hot extrusion with Ti (30–50 nm) amounts 0.58, 0.97 and 1.98 vol. %. The room temperature tensile properties of the synthesized nanocomposites revealed a significant increase in the 0.2%YS (∼79% to ∼112%) and UTS (∼ 46% to ∼81%) when compared to pure magnesium, with decrease in ductility. The addition of 0.97Ti increased the 0.2%CYS of Mg by ∼59% and with 0.58Ti, the UCS of Mg increased by ∼34% with an inappreciable decrease in the ductility [37]. Magnesium matrix (AZ91D) reinforced with TiC-Ti2-AlC-TiB2 (R-Mg) particulates (< 59 μm) was fabricated using an in-situ reactive infiltration technique by Gobara et al. [38]. Electrochemical Impedance Spectroscopy (EIS) and Potentio Dynamic Polarization (PDP) showed that the reinforcing particles greatly increased the strengthened alloy’s corrosion resistance in a 3.5% percent NaCl solution. Potentio Dynamic polarization showed that AZ91D is vulnerable to localized corrosion and a passivating activity was demonstrated by the composite alloy. Polarization resistance values obtained from the EIS study suggested that the composite alloy, R-Mg, showed high activity on the first day of immersion in NaCl due to the initial dissolution of alpha magnesium from the R-Mg surface leaving a more corrosion resistant enhanced matrix (titanium carbides and borides) [38]. Mg60Zn35Ca5 BMGC, 40 vol. % of Ti (75- 105 μm) particles showed a more stable and lower corrosion rate relative to that of the other composites suggesting that the Mg60Zn35Ca5 BMGC releases its Mg ions gradually and uniformly [39]. Meenashisundaram et al.[34] researched Mg 1 vol. % Ti and Mg 1 vol. % of TiB2 composites including Ti (30-50 nm) and TiB2 (~60 nm) nanoparticles which were synthesized using the technique of disintegrated melt deposition (DMD) followed by hot extrusion. Determination of corrosion rates by weight loss technique in Dulbecco’s Modified Eagle’s Medium (DMEM) + 10% Fetal Bovine Serum (FBS) solution revealed that after 28 days of immersion testing, Mg 1 vol.% Ti exhibited the best corrosion resistance followed by pure magnesium and finally by Mg 1 vol.% TiB2 composite. Mg ~ 1 vol. % Ti nanocomposite exhibited zero degradation whereas for pure Mg, after 24 h of immersion, the corrosion rate increased to a maximum of ~ 0.69 mm/year and gradually decreased. The average corrosion rate of Mg -1 vol.% Ti nanocomposite was found to be ~ 0.1150 mm/year for 28 days which is ~ 71% lesser than that of pure Mg [40].

The mechanical and corrosion results discussed above shows that Mg-Ti composite systems can be used in clinical scenario for orthopaedic and dental applications. However, a more systematic approach is required to equally balance the triangle of biocompatibility, mechanical integrity and corrosion resistance. (Table 1) provides a summarized view of different types of titanium-based reinforcements in different magnesium-based matrices.

Traditional Ceramic Reinforcements
Traditional ceramic reinforcements are used due to their wider availability, low cost and chemical inertness in physiological mediums. Accordingly, they are investigated by many researchers. Guo et al. [48] synthesised a (SiC/TiC)p/AZ91 hybrid nanocomposite using slow extrusion speed (1, 0.5 and 0.1 mm/s, ) and at low temperature (270 oC). The addition of 1 wt. % (SiC/TiC)p (40 and 50 nm) nanoparticles hindered the movement of grain boundaries leading to grain refinement. With the addition of nano reinforcements, they reported an enhancement in tensile strengths (YS 345.6 MPa and UTS of 397.2 MPa) of AZ91 alloy [48]. Deng etal.[49]used 1 wt.% SiCp (40 nm) as reinforcement in magnesium matrix and the composite exhibited high strength (∼441MPa) and high modulus (∼60 GPa). The research work conducted so far has established that the size or length scale of the reinforcement significantly influences the strength of the end composite. For example, within micron length scale, smaller the size of the micron particles, better the mechanical strength of the composites [49]. This was also supported by Chen et al. [50,51] who added SiCp particles of 1-2 μm size range to AZ91 alloy and observed a finer grain size and increased strength

and ductility. This was attributed to the fact that smaller the particle size higher is the extent of interfacial bonding between the particles and matrix owing to decreased surface defects around the particles, leading to increased strength [50, 51]. Nie et al. [52], synthesised Mg-4Zn-0.5Ca alloy with addition of low mass fraction of TiC (0.2, 0.5, 1, 2%) nanoparticles (50 nm) using ultrasonic treatment and mechanical stirring. Increasing the amount of TiC decreased the grain size and reduced the secondary phase particles of MgZn and Ca2Mg6Zn. 1 wt. % of TiC composite showed YS of 369.8 MPa and UTS of 393.6 MPa [52]. To note that research activities in magnesium-based composites containing nanoreinforcements have increased in recent times due to the capability of nanoreinforcements to simultaneously increase the combination of mechanical properties such as strength and ductility and corrosion response of the base matrices.

Calcium Phosphate Ceramics (CPC)
For more than 20 years ceramics made from calcium phosphate salts are successfully used to replace and increase bone tissue growth. Hydroxyapatite (HAP) and β-tricalcium phosphate (β-TCP) are the most widely used bio ceramics based on calcium phosphate [53-55]. Hydroxyapatite (HAP) reinforced magnesium matrix has been used for various biomedical applications. HAP reinforced magnesium composites were studied by Gu et al. and the corrosion and mechanical properties of the composites were evaluated [56, 57]. They reported an increase in tensile strength and corrosion resistance with addition of 10 wt. % HAP (2–3 μm)when compared to composites with higher amounts of HAP (20 wt.% and 30 wt.%) [56, 57]. Cui et al. investigated Mg- 2.5 Zn/HAP composites and showed that the addition of 5 and 10 wt.% HAP (60 μm) assists in decreasing corrosion rate and increases the mechanical strength [58]. They reported that addition of 5 wt.% HAP retained the tensile integrity of the structures by 34% and compressive strength by 66 % after 14 days of immersion [59]. Jaiswal et al. reported that addition of 5 wt.% HAP (30 μm) into Mg-3 Zn matrix increased the CYS by 23% and reduced the corrosion rate by 42% [60]. The addition of nano HAP (30 nm) particles to Mg66Zn30Ca4 metallic glass led to marginal improvement in the mechanical properties and increased corrosion resistance of the composite [61]. From the microstructural perspective, addition of HAP nano reinforcement reduced the grain growth and showed grain refinement [26]. Khanra et al. [62, 63] evaluated the microstructure of Mg–HAP and ZM61–HAP composites and reported grain refinement. Xu etal.[64] showed that Mg–HAP (0, 5, 10 and 15 wt.%) exhibits high compressive strength, yield strength and reduced tensile strength when compared to the base matrix (Table 2). (Figure 1) shows typical micrographs illustrating the role of β -TCP in grain boundary pinning and grain refinement (~

70%) leads to an increase in the mechanical strength of a Mg- β -TCP composite [81]. Zheng et al. [82] altered the surfaces of β-TCP nanoparticles to achieve a uniform dispersion in the Mg- Zn-Zr matrix by coating with magnesium oxide (MgO). Uniformly scattered β-TCP nanoparticles strengthened the composites’ mechanical properties by grain refining reinforcement mechanism. CPC particles react with body fluids and encourage the development of new bone tissues that lead to rapid bone growth and can be personalized in vitro and in vivo with Ca2 +, HPO42 and PO43- degradation products [82,83]. Feng et al. [74] studied the microstructures and mechanical integrity of ZK60A (6 wt.% Zn, 0.5 wt.% Zr, bal. Mg) reinforced with 2.5, 5, 7.5, and 10 wt.% CPC particles. The composites containing lower amounts of CPC particles (2.5-5 wt.%) exhibited minimum defects in the fabricated composites resulting in improved corrosion resistance whereas the composites containing 7.5 and 10 wt. % CPC showed voids and cracks upon loading [68].

The presence of β-TCP particles (0.7–4.6 μm) assisted in the corrosion protection of pure Mg. The pH values stabilized for the composites compared to pure Mg and displayed lower corrosion rate (~9 times) with a superior protection displayed by the Mg-1.5 TCP composite as compared to pure Mg [81]. To note here that calcium phosphate ceramics, similar to traditional ceramics, assist in grain refinement, enhance the mechanical properties typically the elastic modulus and enhances corrosion response. However, not all the systems with all reinforcements and length scales will do so and experimental validation will be required for each new system. (Table 2) provides a summarized view of balancing act of different types of reinforcements in different magnesium-based matrices.

Bioglass Reinforcement
Bioactive glass, consisting of a family of glass compositions and capable to bind in a few hours to hard and soft tissues, displays the best-known bioactive actions [84]. These bioactive glasses could gradually degrade after implantation accompanied by the release of ionic products that stimulate bone-related cell proliferation. These advantageous features make the bioactive glass a preferred choice as the reinforcement phase to be added to a Mg-based biomaterial for the enhancement of bioactivity [84, 85].

Nano-SiO2particles (~20 nm) were used as reinforcement in AZ31 magnesium alloy to form AZ31/ SiO₂ composites by friction stir process. Addition of the SiO₂ particles increased the hardness of the matrix to 90 HV when compared to AZ31 alloy hardness of 49HV [86]. Low volume fraction SiO₂ (0.5, 1, and 2 vol. %) nano particle (15 nm) reinforced magnesium composites synthesized using powder metallurgy technique showed marginal decrease in the grain size. There was 32 % decrease in the grain size for 2 vol. % reinforcement (23±1.5) when compared to pure Mg (34±2). The ultimate tensile strength (UTS) for pure Mg progressively increased with the addition of SiO₂ nano- particulates and 2 vol. % SiO₂ showed the maximum UTS of 171 MPa which surpassed the UTS value of pure Mg by 34 % [87]. The ultimate compressive strength (UCS) was 207 ± 3 for 2 vol. % SiO₂ composite when compared to pure Mg with 174 ± 7 MPa. The addition of SiO₂ showed 18.9 % increase in the UCS of the composite [88]. The AM60 magnesium alloy reinforced with 1 and 2 wt. % of SiO₂ nanoparticles (~35 nm) reduced the grain size and increased the hardness of samples from 34.8 HV in AM60 to 51.5 HV in 2 wt.% composite. Improvement of the mechanical properties was attributed to a combination of Orowan, Hall– Petch and load-bearing mechanisms [89]. Corrosion resistance of pure Mg reinforced with bioglass (BG, 45S5) particles (30– 75 μm ) amounts of 5, 10, and 15 wt.% in simulated body fluid (SBF) at 37 °C was studied by Wan et al.[90]. Increasing the amount of bioglass reduced the hydrogen gas evolution from the composite. Accordingly, compared with pure Mg, hydrogen evolution from BG/Mg composites as a result of degradation, was less. Moreover, the hydrogen evolution is dependent on bioglass content. Expectedly, BG-15/Mg with the highest bioglass content showed the lowest hydrogen evolution rate among all composite samples. Addition of bioglass into Mg significantly reduced the pH value from 9.3 for pure Mg to 8.3 for BG-15/Mg [90]. Huan et al. synthesised ZK30 magnesium alloy as the matrix with 5 and 10 wt. % (40 μm) bioactive glass (BG, 45S5) as the reinforcement. Immersion tests in the minimum essential medium (MEM) at 37°C showed that the composites with 5 and 10% BG had lower rates of degradation and hydrogen evolution than the ZK30 magnesium alloy [91]. These results validated that hydrogen evolution and corrosion of BG/Mg composites can be controlled by adjusting the content of bioglass such that various clinical needs may be met.

Nano-carbon Reinforced Magnesium Composites
Carbon Nanotubes (CNTs) are considered as one of the ideal reinforcements due to their high strength, lightweight properties and also due to favourable geometrical properties such as high aspect ratio, high specific surface area and excellent mechanical properties [92-95]. Due to their excellent mechanical strength and corrosion resistance to improve the performance of composite materials, CNTs reinforced materials are widely used in artificial joints and bone fixation materials [96]. CNTs are intended to be used in the orthopaedic field as a locally implanted

biomaterial such as artificial joints or fixation devices. Various studies conducted on the CNTs have reported that the material exhibits high biocompatibility [96-98]. Li et al. [99] synthesised magnesium metal matrix composites containing carbon nanotubes (CNTs) using powder metallurgy process. They reported that addition of 4.0 wt.% CNT increased the microhardness by 43.5% and UTS by 33.4% when compared to pure magnesium samples [99]. Xian et al. fabricated magnesium alloy ZK60 composites containing low amount of graphene nano plates (GNPs) by facile melt stirring and hot extrusion processes. The composite with only 0.05 wt. % GNPs showed enhancement in yield strength up to 256 MPa. The hardness of the graphene reinforced magnesium composites was evaluated and the results showed that the microhardness increases with the increased graphene content. Pure magnesium sample hardness was 59.3±3.0 HV, while magnesium-graphene composites reinforced with 0.05 wt. % graphene showed hardness of 89.9 ± 4.5 HV indicating 51 % increases over unreinforced magnesium. This is attributed to the fact that the graphene gets aligned along the grain boundaries leading to grain boundary pinning effect. The Tensile Yield Strength (TYS) increased by 62% with 0.05 wt. % GNPs, the compressive yield strength (CYS) increased by 98% with 0.05 wt.% GNPs [100, 101]. Compared to pure Mg, Mg–GNP composites containing 0.1wt. % G-15 (15μm) and G-5 (5μm) GNPs showed the best corrosion resistance in the same corrosion environment. In situ formation of a MgH2 phase in Mg–GNP composites containing lower concentrations (0.1wt.%) of G-15 GNPs in the Mg matrices resulted in slower H2 production rates and lower Icorr values [102]. Carbon nanotubes (CNTs) assist in grain refinement and thus assist in increasing the mechanical properties typically the Tensile Yield Strength (TYS) and Compressive Yield Strength (CYS) and an addition also increase the corrosion resistance. However, not all the systems with all reinforcements and length scales will do so and experimentation validation will be required for each new system.

Temporary implant applications need the implant material to be in a desired location in the body without showing rapid degradation and to maintain the mechanical integrity until the purpose of bone formation is fulfilled. Magnesium and its alloys containing different types reinforcements have gained significant attention in last decade as potential materials for temporary implants. Addition of reinforcement in many cases has shown to influence the mechanical and corrosion resistance properties of the magnesium matrix. The amount of addition of reinforcement depends on their length scale. Moreover, addition of many of these reinforcements in magnesium assists in enhancing corrosion resistance and in maintaining the structural integrity of the temporary implants. While the research activities in magnesium-based composites are actively being pursued, much work still needs to be done to understand their corrosion behaviour in-vivo.

No conflict of interest.

1. S Prasadh, S Suresh, KL Hong, A Bhargav, V Rosa, RCW Wong. Biomechanics of alloplastic mandible reconstruction using biomaterials: The effect of implant design on stress concentration influences choice of material. Journal of the Mechanical Behavior of Biomedical Materials. 2020;103:103548. doi.org/10.1016/j.jmbbm.2019.103548
2. C Castellani, RA Lindtner, P Hausbrandt, E Tschegg, SE Tschegg, G Zanoni, et al. Bone–implant interface strength and osseointegration: Biodegradable magnesium alloy versus standard titanium control. Acta biomaterialia. 2011;7(1):432-440.doi: 10.1016/j.actbio.2010.08.020
3. Ehtemam Haghighi, K Prashanth, H Attar, AKChaubey, G Cao, L Zhang. Evaluation of mechanical and wear properties of TixNb7Fe alloys designed for biomedical applications. Materials & Design. 2016;111:592-599.doi:10.1016/j.matdes.2016.09.029
4. M Long, H Rack. Titanium alloys in total joint replacement—a materials science perspective. Biomaterials. 1998;19(18):621-639.doi.org/10.1016/S0142-9612(97)00146-4
5. M Niinomi, CJ Boehlert. Titanium alloys for biomedical applications, Advances in Metallic Biomaterials. Springer. 2015;pp:179-213.
6. R Antunes, ARodas, N Lima, O Higa, Costa. Study of the corrosion resistance and in vitro biocompatibility of PVD TiCN-coated AISI 316 L austenitic stainless steel for orthopedic applications. Surface and Coatings Technology. 2010;205(7):2074-2081.
7. XN Gu, YF Zheng, A review on magnesium alloys as biodegradable materials. Frontiers of Materials Science in China. 2010;4(2):111-115.
8. M. Niinomi, M. Nakai, Titanium-based biomaterials for preventing stress shielding between implant devices and bone, International journal of biomaterials 2011
9. S Ozan, J Lin, Y Li, Y Zhang, K Munir, H Jiang, et al. Deformation mechanism and mechanical properties of a thermomechanically processed β Ti–28Nb–35.4 Zr alloy. Journal of the mechanical behavior of biomedical materials. 2018;78:224-234.doi: 10.1016/j.jmbbm.2017.11.025
10. A Sanaty-Zadeh. Comparison between current models for the strength of particulate-reinforced metal matrix nanocomposites with emphasis on consideration of Hall–Petch effect. Materials Science and Engineering. 2012;531:112-118.doi.org/10.1016/j.msea.2011.10.043
11. H Windhagen, K Radtke, A Weizbauer, J Diekmann, Y Noll, U Kreimeyer.Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study. Biomedical engineering online. 2013;12(1):62.doi: 10.1186/1475-925X-12-62
12. S Prasadh, V Ratheesh, V Manakari, G Parande, M Gupta, R Wong. The Potential of Magnesium Based Materials in Mandibular Reconstruction. Metals. 2019;9(3):302.doi.org/10.3390/met9030302
13. O Duygulu, RA Kaya, G Oktay, AA Kaya. Investigation on the potential of magnesium alloy AZ31 as a bone implant, Materials Science Forum. Trans Tech Publ. 2007:421-424.doi.org/10.4028/www.scientific.net/MSF.546-549.421
14. SV Dorozhkin. Calcium orthophosphate coatings on magnesium and its biodegradable alloys. Acta biomaterialia. 2014;10(7):2919-2934.doi.org/10.1016/B978-1-78242-078-1.00007-4
15. F Witte, N Hort, C Vogt, S Cohen, KU Kainer, R Willumeit. Degradable biomaterials based on magnesium corrosion. Current Opinion in Solid State and Materials Science. 2008;12(5-6):63-72.doi.org/10.1016/j.cossms.2009.04.001
16. MP Staiger, AM Pietak, J Huadmai, G Dias. Magnesium and its alloys as orthopedic biomaterials: a review.Biomaterials. 2006;27(9):1728-1734.
17. X Gu, Y Zheng, Y Cheng, S Zhong, T Xi. In vitro corrosion and biocompatibility of binary magnesium alloys. Biomaterials. 2009;30(4):484-98.doi: 10.1016/j.biomaterials.2008.10.021
18. J Walker, Shadanbaz, TB Woodfield, MP Staiger, GJ Dias. Magnesium biomaterials for orthopedic application: a review from a biological perspective. J Biomed Mater Res B Appl Biomater. 2014;102(6):1316-1331.doi: 10.1002/jbm.b.33113
19. PC Wong, PH Tsai, CK Cheng, JSC Jang, JC Huang. Degradation behavior and mechanical strength of Mg-Zn-Ca bulk metallic glass composites with Ti particles as biodegradable materials. Journal of Alloys and Compounds 2017;699:914-920.doi.org/10.1016/j.jallcom.2017.01.010
20. D Henry. Materials and coatings for medical devices: cardiovascular, ASM International, Ohio, USA.  2009;151-186.
21. MB Kannan. 13 - Hydroxyapatite coating on biodegradable magnesium and magnesium-based alloys, in: M. Mucalo (Ed.), Hydroxyapatite (Hap) for Biomedical Applications. Woodhead Publishing. 2015:289-306.
22. Q Tian, J Lin, L, Castaneda, A Tsanhani, ZS Dunn, A Rodriguez. Nano-to-Submicron Hydroxyapatite Coatings for Magnesium-based Bioresorbable Implants – Deposition, Characterization, Degradation, Mechanical Properties, and Cytocompatibility. Scientific Reports. 2019;9(1):810
23. Q Nguyen, M Gupta. Enhancing compressive response of AZ31B magnesium alloy using alumina nanoparticulates. Composites Science and Technology. 2008;68(10-11):2185-2192.doi.org/10.1016/j.compscitech.2008.04.020
24. RK Roeder, CH Turner. Composite biomaterial including anisometric calcium phosphate reinforcement particles and related methods. Google Patents. 2010
25. HH Xu, L Sun, MD Weir, S Takagi, L Chow, B Hockey. Effects of incorporating nanosized calcium phosphate particles on properties of whisker‐reinforced dental composites. Journal of Biomedical Materials Research Part B: Applied Biomaterials: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials. 2007;81(1):116-125.doi: 10.1002/jbm.b.30644
26. S Prasadh, V Manakari, G Parande, T Srivatsan, R Wong, M Gupta. Bioresorbable Nano-Hydroxyapatite Reinforced Magnesium Alloplastic Bone Substitute for Biomedical Applications: A Study, Nanocomposites VI: Nanoscience and Nanotechnology in Advanced Composites. Springer. 2019:71-82
27. K Bordji, J Jouzeau, D Mainard, E Payan, P Netter, K Rie, et al. Cytocompatibility of Ti-6Al-4V and Ti-5Al-2.5 Fe alloys according to three surface treatments, using human fibroblasts and osteoblasts. Biomaterials. 1996;17(9):929-940.doi.org/10.1016/0142-9612(96)83289-3
28. M Gupta, GK Meenashisundaram. Insight into designing biocompatible magnesium alloys and composites: processing, mechanical and corrosion characteristics. Springer. 2015
29. EP Ivanova, K Bazaka, RJ Crawford. New functional biomaterials for medicine and healthcare, Woodhead publishing New Delhi, India. 2014
30. H Kaneko, M Uchida, HM Kim, T Kokubo, T Nakamura. Process of apatite formation induced by anatase on titanium metal in simulated body fluid, Key Engineering Materials. Trans Tech Publ. 2002;pp:649-652.doi: 10.4028/www.scientific.net/KEM.218-220.649
31. HM Kim, F Miyaji, T Kokubo, T Nakamura. Preparation of bioactive Ti and its alloys via simple chemical surface treatment. Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials and The Japanese Society for Biomaterials. 1996;32(3):409-417.doi: 10.1002/(SICI)1097-4636(199611)32:3<409::AID-JBM14>3.0.CO;2-B
32. T Kokubo, F Miyaji, HM Kim, T Nakamura. Spontaneous formation of bonelike apatite layer on chemically treated titanium metals. Journal of the American Ceramic Society. 1996;79(4):1127-1129.doi.org/10.1111/j.1151-2916.1996.tb08561.x
33. J Marchi, EM Amorim, DR Lazar, V Ussui, AHA Bressiani, PF Cesar. Physico-chemical characterization of zirconia–titania composites coated with an apatite layer for dental implants. Dental Materials. 2013;29(9):954-962.doi.org/10.1016/j.dental.2013.07.002
34. F Aydin, Y Sun. Investigation of wear behaviour and microstructure of hot-pressed TiB2 particulate-reinforced magnesium matrix composites. Canadian Metallurgical Quarterly. 2018;57(4):455-469.doi: 10.1080/00084433.2018.1478491
35. GK Meenashisundaram, MH Nai, M Gupta. Effects of primary processing techniques and significance of hall-petch strengthening on the mechanical response of magnesium matrix composites containing TiO2 nanoparticulates. Nanomaterials. 2015;5(3):1256-1283.doi: 10.3390/nano5031256
36. GK Meenashisundaram, MH Nai, A Almajid, M Gupta. Reinforcing low-volume fraction nano-TiN particulates to monolithical, pure Mg for enhanced tensile and compressive response. Materials. 2016;9(3):134.doi: 10.3390/ma9030134
37. GK Meenashisundaram, M Gupta. Low volume fraction nano-titanium particulates for improving the mechanical response of pure magnesium. Journal of alloys and compounds. 2014;593:176-183.doi: 10.1016/j.jallcom.2013.12.157
38. M Gobara, M Shamekh, R Akid. Improving the corrosion resistance of AZ91D magnesium alloy through reinforcement with titanium carbides and borides. Journal of Magnesium and Alloys. 2015;3(2):112-120.doi.org/10.1016/j.jma.2015.03.002
39. PC Wong, PH Tsai, TH Li, CK Cheng, J Jang, J Huang. Degradation behavior and mechanical strength of Mg-Zn-Ca bulk metallic glass composites with Ti particles as biodegradable materials. Journal of Alloys and Compounds. 2017;699:914-920.doi: 10.1016/j.jallcom.2017.01.010
40. GK Meenashisundaram, MH Nai, M Gupta. Effects of Ti and TiB 2 nanoparticulates on room temperature mechanical properties and in vitro degradation of pure Mg, Magnesium Technology 2015. Springer. 2015;pp:413-418.doi.org/10.1007/978-3-319-48185-2_77
41. GK Meenashisundaram, MH Nai, A Almajid, KA Khalil, HS Abdo, M Gupta. Effects of TiO2 powder morphology on the mechanical response of pure magnesium: 1D nanofibers versus 0D nanoparticulates, Journal of alloys and compounds. 2016;664:45-58.doi.org/10.1016/j.jallcom.2015.12.176
42. G. Radhakrishnan, P Anirudh, SA Kumar. Mechanical behavior of nanoparticulate TiO2 reinforced magnesium matrix composite. IOP Conference Series: Materials Science and Engineering, IOP Publishing. 2019;012006
43. B Sahoo, S Panigrahi. Synthesis, characterization and mechanical properties of in-situ (TiC-TiB2) reinforced magnesium matrix composite. Materials & Design. 2016;109:300-313.doi.org/10.1016/j.matdes.2016.07.024
44. GK Meenashisundaram, MH Nai, A Almajid, M Gupta. Development of high performance Mg–TiO2 nanocomposites targeting for biomedical/structural applications. Materials & Design. 2015;65:104-114.doi.org/10.1016/j.matdes.2014.08.041
45. P Xiao, Y Gao, C Yang, Z Liu, Y Li, F Xu. Microstructure, mechanical properties and strengthening mechanisms of Mg matrix composites reinforced with in situ nanosized TiB2 particles. Materials Science and Engineering: A. 2018;710:251-259.doi.org/10.1016/j.msea.2017.10.107
46. THD Ong, N Yu, GK Meenashisundaram, B Schaller, M Gupta. Insight into cytotoxicity of Mg nanocomposites using MTT assay technique. Materials Science and Engineering. 2017;78:647-652.doi: 10.1016/j.msec.2017.04.129
47. GK Meenashisundaram, S Seetharaman, M Gupta. Enhancing overall tensile and compressive response of pure Mg using nano-TiB2 particulates. Materials characterization. 2014;94:178-188.doi.org/10.1016/j.matchar.2014.05.021
48. Y Guo, K Nie, X. Kang, K. Deng, J Han, Z. Zhu. Achieving high-strength magnesium matrix nanocomposite through synergistical effect of external hybrid (SiC+ TiC) nanoparticles and dynamic precipitated phase. Journal of Alloys and Compounds. 2019;771:847-856.doi.org/10.1016/j.jallcom.2018.09.030
49. KK Deng, CJ Wang, KB Nie, XJ Wang. Recent Research on the Deformation Behavior of Particle Reinforced Magnesium Matrix Composite: A Review. Acta Metallurgica Sinica (English Letters). 2019;32(4):413-425.
50. L Chen, Y Yao. Processing, microstructures, and mechanical properties of magnesium matrix composites: a review. Acta Metallurgica Sinica (English Letters). 2014;27(5):762-774
51. LY Chen, D Weiss, J Morrow, JQ Xu, XC Li. A novel manufacturing route for production of high-performance metal matrix nanocomposites. Manufacturing Letters. 2013;1(2-4):62-65.doi.org/10.1016/j.mfglet.2013.10.010
52. Kb Nie, Yc Guo, P Munroe, Kk Deng, Xk Kang. Microstructure and tensile properties of magnesium matrix nanocomposite reinforced by high mass fraction of nano-sized particles including TiC and MgZn2. Journal of Alloys and Compounds. 2020;819:153348.doi: 10.1016/j.jallcom.2018.09.030
53. W Song, M Tian, F Chen, Y Tian, C Wan, X Yu. The study on the degradation and mineralization mechanism of ion‐doped calcium polyphosphate in vitro, Journal of Biomedical Materials Research Part B: Applied Biomaterials: An Official Journal of The Society for Biomaterials. The Japanese Society for Biomaterials and The Australian Society for Biomaterials and the Korean Society for Biomaterials. 2009;89(2):430-438.doi: 10.1002/jbm.b.31230
54. K Wang, F Chen, C Liu, C Rüssel. The effect of polymeric chain-like structure on the degradation and cellular biocompatibility of calcium polyphosphate. Materials Science and Engineering: C. 2008;28(8):1572-1578.doi.org/10.1016/j.msec.2008.04.017
55. G Parande, V Manakari, SPrasadh, D Chauhan, S Rahate, R Wong, et al. Strength retention, corrosion control and biocompatibility of Mg–Zn–Si/HA nanocomposites. Journal of the Mechanical Behavior of Biomedical Materials. 2020;103:103584.doi.org/10.1016/j.jmbbm.2019.103584
56. X Gu, N Li, W Zhou, Y Zheng, X Zhao, Q Cai,et al. Corrosion resistance and surface biocompatibility of a microarc oxidation coating on a Mg–Ca alloy. Acta Biomaterialia. 2011;7(4):1880-1889.doi.org/10.1016/j.actbio.2010.11.034
57. X Gu, W Zhou, Y Zheng, L Dong, Y Xi, D Chai. Microstructure, mechanical property, bio-corrosion and cytotoxicity evaluations of Mg/HA composites. Materials Science and Engineering: C. 2010;30(6):827-832.doi: 10.1016/j.msec.2010.03.016
58. Z Cui, W Li, LCheng, D Gong, W Cheng, W Wang. Effect of nano-HA content on the mechanical properties, degradation and biocompatible behavior of Mg-Zn/HA composite prepared by spark plasma sintering. Materials Characterization. 2019;151:620-631.doi.org/10.1016/j.matchar.2019.03.048
59. A Dubey, S Jaiswal, D Lahiri. Mechanical Integrity of Biodegradable Mg–HA Composite During In Vitro Exposure. Journal of Materials Engineering and Performance. 2019;28(2):800-809
60. S Jaiswal, RM Kumar, P Gupta, M Kumaraswamy, P Roy, D Lahiri. Mechanical, corrosion and biocompatibility behaviour of Mg-3Zn-HA biodegradable composites for orthopaedic fixture accessories. Journal of the mechanical behavior of biomedical materials. 2018;78:442-454.doi.org/10.1016/j.jmbbm.2017.11.030
61. M Ramya, MM Pillai, R Selvakumar, B Raj, K Ravi. Hydroxyapatite particle (HAp) reinforced biodegradable Mg-Zn-Ca metallic glass composite for bio-implant applications. Biomedical Physics & Engineering Express. 2018;4(2): 025039
62. AK Khanra, HC Jung, KS Hong, KS Shin. Comparative property study on extruded Mg–HAP and ZM61–HAP composites. Materials Science and Engineering: A. 2010;527(23):6283-6288.doi.org/10.1016/j.msea.2010.06.031
63. AK Khanra, HC Jung, SH Yu, KS Hong, KS Shin. Microstructure and mechanical properties of Mg-HAP composites. Bulletin of Materials Science.  2010;33(1):43-47
64. L Xu, F Pan, G Yu, L Yang, E Zhang K Yang. In vitro and in vivo evaluation of the surface bioactivity of a calcium phosphate coated magnesium alloy. Biomaterials.  2009;30(8):1512-1523.doi.org/10.1016/j.biomaterials.2008.12.001
65. Campo, B Savoini, L Jordao, A Muñoz, M Monge. Cytocompatibility, biofilm assembly and corrosion behavior of Mg-HAP composites processed by extrusion. Materials Science and Engineering: C. 2017;78:667-673.doi.org/10.1016/j.msec.2017.04.143
66. R. Del Campo, B. Savoini, A. Muñoz, M. Monge, G. Garcés. Mechanical properties and corrosion behavior of Mg–HAP composites, Journal of the mechanical behavior of biomedical materials 39,2014,238-246.doi: 10.1016/j.jmbbm.2014.07.014
67. Campo, B. Savoini, A. Munoz, M. Monge, R. Pareja. Processing and mechanical characteristics of magnesium-hydroxyapatite metal matrix biocomposites. Journal of the mechanical behavior of biomedical materials. 2017;69:135-143.doi.org/10.1016/j.jmbbm.2016.12.023
68. BR Sunil, TS Kumar, U Chakkingal, V Nandakumar, M Doble. Nano-hydroxyapatite reinforced AZ31 magnesium alloy by friction stir processing: a solid state processing for biodegradable metal matrix composites. Journal of Materials Science: Materials in Medicine. 2014;25(4):975-988.doi: 10.1007/s10856-013-5127-7
69. BR Sunil, C Ganapathy, TS Kumar, U Chakkingal. Processing and mechanical behavior of lamellar structured degradable magnesium–hydroxyapatite implants. Journal of the mechanical behavior of biomedical materials. 2014;40:178-189.doi.org/10.1016/j.jmbbm.2014.08.016
70. DB Liu, MF Chen, XY Ye. Fabrication and corrosion behavior of HA/Mg-Zn biocomposites. Frontiers of Materials Science in China. 2010;4(2):139-144
71. F Witte, F Feyerabend, P Maier, J Fischer, M Störmer, C Blawert, et al. Biodegradable magnesium–hydroxyapatite metal matrix composites. Biomaterials. 2007;28(13):2163-2174
72. H Dieringa, L Fuskova, D Fechner, C Blawert. Mechanical and corrosion behaviour of a hydroxyapatite reinforced magnesium alloy WE43, Proceedings of the 17th International Conference on Composite Materials. ICCM, Edinburgh, UK. 2009;pp.:27-31
73. X Ye, M Chen, M Yang, J Wei, D Liu. In vitro corrosion resistance and cytocompatibility of nano-hydroxyapatite reinforced Mg–Zn–Zr composites. Journal of Materials Science: Materials in Medicine. 2010;21(4):1321-1328.doi: 10.1007/s10856-009-3954-3
74. A Feng, Y Han. The microstructure, mechanical and corrosion properties of calcium polyphosphate reinforced ZK60A magnesium alloy composites. Journal of Alloys and Compounds. 2010;504(2):585-593.doi.org/10.1016/j.jallcom.2010.06.013
75. D Liu, Y Zuo, W Meng, M Chen, Z Fan. Fabrication of biodegradable nano-sized β-TCP/Mg composite by a novel melt shearing technology. Materials Science and Engineering: C. 2012;32(5):1253-1258.doi.org/10.1016/j.msec.2012.03.017
76. DB Liu, Y Huang, P Prangnell. Microstructure and performance of a biodegradable Mg–1Ca–2Zn–1TCP composite fabricated by combined solidification and deformation processing. Materials Letters. 2012;82:7-9.doi.org/10.1016/j.matlet.2012.05.035
77. SY He, S Yue, MF Chen, DB Liu, XY Ye. Microstructure and properties of biodegradable β-TCP reinforced Mg-Zn-Zr composites. Transactions of Nonferrous Metals Society of China. 2011;21(4):814-819.doi.org/10.1016/S1003-6326(11)60786-3
78. X Wang, L Dong, J Li, X Li, X Ma, Y Zheng. Microstructure, mechanical property and corrosion behavior of interpenetrating (HA+ β-TCP)/MgCa composite fabricated by suction casting. Materials Science and Engineering: C. 2013;33(7):4266-4273.doi.org/10.1016/j.msec.2013.06.018
79. X Gu, X Wang, N Li, L Li, Y Zheng, X Miao. Microstructure and characteristics of the metal–ceramic composite (MgCa‐HA/TCP) fabricated by liquid metal infiltration. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2011;99(1):127-134.doi: 10.1002/jbm.b.31879
80. X Ma, L Dong, X Wang. Microstructure, mechanical property and corrosion behavior of co-continuous β-TCP/MgCa composite manufactured by suction casting. Materials & Design. 2014;56:305-312.doi.org/10.1016/j.matdes.2013.11.041
81. G. Parande, V. Manakari, H. Gupta, M. Gupta. Magnesium-β-tricalcium phosphate composites as a potential orthopedic implant: A mechanical/damping/immersion perspective, Metals 8(5),2018,343.doi.org/10.3390/met8050343
82. H Zheng, Z Li, C You, D Liu, M Chen. Effects of MgO modified β-TCP nanoparticles on the microstructure and properties of β-TCP/Mg-Zn-Zr composites. Bioactive materials. 2017;2(1):1-9.doi: 10.1016/j.bioactmat.2016.12.004
83. VK Bommala, MG Krishna, CT Rao. Magnesium matrix composites for biomedical applications: A review.Journal of Magnesium and Alloys. 2019;7(1):72-79.doi.org/10.1016/j.jma.2018.11.001
84. J Schrooten, J Helsen. Adhesion of bioactive glass coating to Ti6Al4V oral implant. Biomaterials. 2000;21(4):1461-1469.doi: 10.1016/s0142-9612(00)00027-2
85. P Sepulveda, J.R. Jones, L.L. Hench. Bioactive sol‐gel foams for tissue repair, Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials. The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials. 2002;59(2):340-348.doi: 10.1002/jbm.1250
86. Y Jiang, X Yang, H Miura, T Sakai. Particles reinforced magnesium alloy produced by friction stir processing. Rev Adv Mater Sci. 2013;33:29-32
87. G Parande, V Manakari, GK Meenashisundaram, M Gupta. Enhancing the tensile and ignition response of monolithic magnesium by reinforcing with silica nanoparticulates. Journal of Materials Research. 2017;32(11):2169-2178.doi.org/10.1557/jmr.2017.194
88. G Parande, V Manakari, GK Meenashisundaram, M Gupta. Enhancing the hardness/compression/damping response of magnesium by reinforcing with biocompatible silica nanoparticulates. International Journal of Materials Research. 2016;107(12):1091-1099.doi.org/10.1557/jmr.2017.194
89. F Barati, M Latifi, MH Mosallanejad, A Saboori. Novel AM60-SiO2 Nanocomposite Produced via Ultrasound-Assisted Casting; Production and Characterization. Materials. 2019;12(23):3976.doi: 10.3390/ma12233976
90. Y Wan, T Cui, W Li, C Li, J Xiao, Y Zhu,et al. Mechanical and biological properties of bioglass/magnesium composites prepared via microwave sintering route. Materials & Design. 2016;99:521-527.doi.org/10.1016/j.matdes.2016.03.096
91. Z Huan, S Leeflang, J Zhou, W Zhai, J Chang, J Duszczyk. In vitro degradation behavior and bioactivity of magnesium‐Bioglass® composites for orthopedic applications. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2012;100(2):437-446.doi: 10.1002/jbm.b.31968
92. C Li, TW Chou. A structural mechanics approach for the analysis of carbon nanotubes. International journal of solids and structures. 2003;40(10):2487-2499.doi.org/10.1016/S0020-7683(03)00056-8
93. MJ Treacy, TW Ebbesen, JM Gibson. Exceptionally high Young's modulus observed for individual carbon nanotubes. nature. 199;381(6584):678-680
94. EW Wong, PE Sheehan, CM Lieber. Nanobeam mechanics: elasticity, strength, and toughness of nanorods and nanotubes, science. 1997;277(5334):1971-1975.doi: 10.1126/science.277.5334.1971
95. MF Yu, O Lourie, MJ Dyer, K Moloni, F Kelly, R Ruoff. Strength and breaking mechanism of multiwalled carbon nanotubes under tensile load. Science. 2000;287(5453):637-640.doi: 10.1126/science.287.5453.637
96. KT Blanchard, C Barthel, JE French, HE Holden, R Moretz, FD Pack, et al. Transponder-induced sarcoma in the heterozygous p53+/-mouse. Toxicologic pathology. 1999;27(5):519-527.doi: 10.1177/019262339902700505
97. A Takagi, A Hirose, M Futakuchi, H Tsuda, J Kanno. Dose‐dependent mesothelioma induction by intraperitoneal administration of multi‐wall carbon nanotubes in p53 heterozygous mice. Cancer Science. 2012;103(8):1440-1444.doi: 10.1111/j.1349-7006.2012.02318.x
98. A Takagi, A Hirose, T Nishimura, N Fukumori, A Ogata, N Ohashi.et al. Induction of mesothelioma in p53+/− mouse by intraperitoneal application of multi-wall carbon nanotube. The Journal of toxicological sciences. 2008;33(1):105-116.doi: 10.2131/jts.33.105
99. H Li, X Dai, L Zhao, B Li, H Wang, C Liang, J Fan. Microstructure and properties of carbon nanotubes-reinforced magnesium matrix composites fabricated via novel in situ synthesis process. Journal of Alloys and Compounds. 2019;785:146-155.doi.org/10.1016/j.jallcom.2019.01.144
100. X Du, W Du, Z Wang, K Liu, S Li. Ultra-high strengthening efficiency of graphene nanoplatelets reinforced magnesium matrix composites. Materials Science and Engineering: A. 2018;711:633-642.doi.org/10.1016/j.msea.2017.11.040
101. X Du, K Zhen, F Liu. Graphene reinforced magnesium matrix composites by hot pressed sintering. Dig J Nanomater Bios. 2018;13:827-833
102. K Munir, C Wen, Y Li. Graphene nanoplatelets-reinforced magnesium metal matrix nanocomposites with superior mechanical and corrosion performance for biomedical applications. Journal of Magnesium and Alloys. 2020. doi.org/10.1016/j.jma.2019.12.002