Graphene Family Nanomaterial Reinforced Magnesium-Based Matrix Composites for Biomedical Application: A Comprehensive Review

: Together with the enhancement of the load-bearing implant process for bone substitution and reproduction, an increasing requirement was observed concerning biodegradable magnesium and its alloys with lighter density and outstanding characteristics. Regardless of the current great potential of Mg utilization currently, the broader use of Mg alloys continues to be constrained by several natural causes, such as low resistance of corrosion, inadequate mechanical integrity during the healing process, and poor antibacterial performance. In this perspective, Mg-based composite encapsulated within graphene family nanomaterials (GFNs) such as graphene (Gr), graphene oxide (GO), graphene nanoplatelets (GNPs), and reduced graphene oxide (rGO) as reinforcement agents present great antibacterial activity, as well as cellular response and depicted numerous beneﬁts for biomedical use. Magnesium matrix nanocomposites reinforced with GFNs possess enhanced mechanical properties and high corrosion resistance (low concentration graphene). It is worth noting that numerous elements including the production technique of the Mg-based composite containing GFNs and the size, distribution, and amounts of GFNs in the Mg-based matrix have a crucial role in their properties and applications. Then, the antibacterial mechanisms of GFN-based composite are brieﬂy described. Subsequently, the antibacterial and strengthening mechanisms of GFN-embedded Mg-based composites are brieﬂy described. This review article is designed to wrap up and explore the most pertinent research performed in the direction of Mg-based composites encapsulated within GFNs. Feasible upcoming investigation directions in the ﬁeld of GFN-embedded Mg-based composites are discussed in detail.


Introduction
The requirement for impressive metallic biomaterials for synthetic implants is mounting continuously and is anticipated to increase to meet the requirements of consumers with bone injuries and deterioration resulting from accidents, sports-related accidental injuries, or the typical course of elevate the ductility of metal matrices as they demonstrate outstanding mechanical characteristics and have a lower inclination to agglomerate in comparison with other carbon nanomaterials including CNTs and ball-shaped fullerenes [22,23]. Graphene has distinctive characteristics that allow it to be more useful. First of all, it has substantial stability in chemical and thermal circumstances [31]. Subsequently, an intuitive penetration barrier among the protected metal and reactants might be created through the surfaces of the sp 2 carbon allotropes [32,33]. It was likewise revealed [34] that the bacterial cytotoxicity of GFNs could be assigned to both membrane and oxidative stress. The GFNs are inclined to trigger cellular deposition, since it is more probable to interact with bacterial cells as a result of its greater density of functional groups (FGs) and small size [35]. The GFN nanosheets may destroy the cell caused by stress induction of its membrane layer, which results in interrupting and destroying the cell walls [34]. Consequently, it is crucial to evaluate the latest studies in these fields and sum up their results. Figure 1 [31] depicts a schematic regarding some applications of GFNs including biosensors, phototherapy, tissue engineering (TE), gene and drug delivery, and the formation of coating layers on metallic implants. In this review article, we summarize the mechanical, corrosion, and biological characteristics of recent studies regarding Mg-based matrix composites containing GNPs. We additionally offer our points of views on the forthcoming fabrication methods and development of Mg-based matrix composites containing GFNs pertaining to biodegradable implant purposes.
Metals 2020, 10, 1002 3 of 40 demonstrate outstanding mechanical characteristics and have a lower inclination to agglomerate in comparison with other carbon nanomaterials including CNTs and ball-shaped fullerenes [22,23]. Graphene has distinctive characteristics that allow it to be more useful. First of all, it has substantial stability in chemical and thermal circumstances [31]. Subsequently, an intuitive penetration barrier among the protected metal and reactants might be created through the surfaces of the sp 2 carbon allotropes [32,33]. It was likewise revealed [34] that the bacterial cytotoxicity of GFNs could be assigned to both membrane and oxidative stress. The GFNs are inclined to trigger cellular deposition, since it is more probable to interact with bacterial cells as a result of its greater density of functional groups (FGs) and small size [35]. The GFN nanosheets may destroy the cell caused by stress induction of its membrane layer, which results in interrupting and destroying the cell walls [34]. Consequently, it is crucial to evaluate the latest studies in these fields and sum up their results. Figure 1 [31] depicts a schematic regarding some applications of GFNs including biosensors, phototherapy, tissue engineering (TE), gene and drug delivery, and the formation of coating layers on metallic implants. In this review article, we summarize the mechanical, corrosion, and biological characteristics of recent studies regarding Mg-based matrix composites containing GNPs. We additionally offer our points of views on the forthcoming fabrication methods and development of Mg-based matrix composites containing GFNs pertaining to biodegradable implant purposes.

Development of Mg-Based Biodegradable Metals
Magnesium and its alloys tend to be extremely lightweight metals with density varying from 1.74 to 2.0 g/cm 3 , which is certainly lower in comparison with the non-degradable Ti alloy (4.4-4.5 g/cm 3 ) and almost similar to bone (1.8-2.1 g/cm 3 ) [14]. The fracture toughness of magnesium is more significant in comparison with ceramic-based components, although the elastic modulus (41)(42)(43)(44)(45) GPa) is similar to bone, a fact that reduces the risk for stress shielding occurrence. Mg is fundamental reproduced from [31], with permission Elsevier, 2019.

Development of Mg-Based Biodegradable Metals
Magnesium and its alloys tend to be extremely lightweight metals with density varying from 1.74 to 2.0 g/cm 3 , which is certainly lower in comparison with the non-degradable Ti alloy (4.4-4.5 g/cm 3 ) and almost similar to bone (1.8-2.1 g/cm 3 ) [14]. The fracture toughness of magnesium is more significant in comparison with ceramic-based components, although the elastic modulus (41)(42)(43)(44)(45) is similar Metals 2020, 10, 1002 4 of 41 to bone, a fact that reduces the risk for stress shielding occurrence. Mg is fundamental to human metabolism and is a plentiful cation in the body system, with approximately 25 g Mg saved in the body system and roughly a part of the total content saved in bone tissue. Mg is likewise a cofactor for numerous enzymes and stabilizes the structures of DNA and RNA [14,36]. Magnesium is a kind of active metal with high corrosion potential (−2.37 V), and pristine magnesium metal reveals actually a lower anticorrosion property in the SBF solution with Cl − [37]. To address this issue and extended the applications of Mg-based alloys, several approaches have been considered including alloying, heat treatment and cold/hot working, powder metallurgy (PM), and surface treatment. Among these, Mg-based composites fabricated with the PM method present versatile mechanical and anticorrosion characteristics attained via the choice of the range of the reinforcement phase.
In this context, Mg and its alloys have been examined as implant materials for several human trials since 1878, which continue to be reviewed by Witte [38] in terms of their historical background. Nevertheless, industrial implant products are not really accessible on the medical market. The historical background concerning clinical examination of Mg-based orthopedic devices since 1900 is shown in Figure 2 [39]. Up to 1980, Mg-based materials were typically priced too high to manufacture; a feasible fabrication process and the resulting mechanical characteristics were restricted; and numerous unsettled issues in connection with the high corrosion rate remain. It is shocking that in the previous decades, no clinical trial report was found regarding Mg pertaining to implant applications [30,39]. Currently, there is a new anticipation pertaining to a wide range of novel technologies regarding Mg alloys' utilization in mass production. There is certainly a demand for a novel class of biomaterials for revolutionary implants and tissue scaffolds that should be in a position to promote the healing rate of damaged tissues at the molecular level [40][41][42][43][44]. In numerous situations, the body requires an implant merely for short-term applications, wherein materials presenting a biodegradable behavior are considered a better strategy compared to stable and inert ones. The perfect biodegradable material, for instance in bone reproduction methods (polymer, ceramic, metal, or composite), has to offer sufficient mechanical fixation, full degradation at the time when it is no longer required, and total substitution by fresh bone tissue [44].
Metals 2020, 10, 1002 4 of 40 to human metabolism and is a plentiful cation in the body system, with approximately 25 g Mg saved in the body system and roughly a part of the total content saved in bone tissue. Mg is likewise a cofactor for numerous enzymes and stabilizes the structures of DNA and RNA [14,36]. Magnesium is a kind of active metal with high corrosion potential (−2.37 V), and pristine magnesium metal reveals actually a lower anticorrosion property in the SBF solution with Cl − [37]. To address this issue and extended the applications of Mg-based alloys, several approaches have been considered including alloying, heat treatment and cold/hot working, powder metallurgy (PM), and surface treatment. Among these, Mg-based composites fabricated with the PM method present versatile mechanical and anticorrosion characteristics attained via the choice of the range of the reinforcement phase.
In this context, Mg and its alloys have been examined as implant materials for several human trials since 1878, which continue to be reviewed by Witte [38] in terms of their historical background. Nevertheless, industrial implant products are not really accessible on the medical market. The historical background concerning clinical examination of Mg-based orthopedic devices since 1900 is shown in Figure 2 [39]. Up to 1980, Mg-based materials were typically priced too high to manufacture; a feasible fabrication process and the resulting mechanical characteristics were restricted; and numerous unsettled issues in connection with the high corrosion rate remain. It is shocking that in the previous decades, no clinical trial report was found regarding Mg pertaining to implant applications [30,39]. Currently, there is a new anticipation pertaining to a wide range of novel technologies regarding Mg alloys' utilization in mass production. There is certainly a demand for a novel class of biomaterials for revolutionary implants and tissue scaffolds that should be in a position to promote the healing rate of damaged tissues at the molecular level [40][41][42][43][44]. In numerous situations, the body requires an implant merely for short-term applications, wherein materials presenting a biodegradable behavior are considered a better strategy compared to stable and inert ones. The perfect biodegradable material, for instance in bone reproduction methods (polymer, ceramic, metal, or composite), has to offer sufficient mechanical fixation, full degradation at the time when it is no longer required, and total substitution by fresh bone tissue [44].

Mg-Based Biocomposites and Bio-Alloys
Mg-based bio-alloys are considered to degrade throughout the body system at a suitable degradation rate; however, they likewise possess the issue of a rapid degradation rate throughout tissue regeneration, which restricts their use for clinical purposes [45]. Mg-based alloys likewise are considered as a great option in the areas of tissue engineering, orthopedics, and cardiovascular stents as a result of their appropriate mechanical characteristic, cytocompatibility, and suitable corrosion rate [46]. The biocompatibility of a metallic biomaterial is its capability to function with an

Mg-Based Biocomposites and Bio-Alloys
Mg-based bio-alloys are considered to degrade throughout the body system at a suitable degradation rate; however, they likewise possess the issue of a rapid degradation rate throughout tissue regeneration, which restricts their use for clinical purposes [45]. Mg-based alloys likewise are considered as a great option in the areas of tissue engineering, orthopedics, and cardiovascular stents as a result of their appropriate mechanical characteristic, cytocompatibility, and suitable corrosion rate [46]. The biocompatibility of a metallic biomaterial is its capability to function with an appropriate host reaction throughout its designed clinical utilization in a body system. The interaction between host tissue, the performance of the metallic implant, and its material characteristics regulate the biocompatibility of an implant, as demonstrated in Figure 3 [47]. The biological reaction of this kind of implant might alter with any specific post-implantation modifications in the host tissue. These biological reactions rely on the chemical and physical characteristics of an implant, the kinds and regions of host tissues that are subjected to an implant, the length of the exposure, the implant's surface characteristics, structure, and forces employed on synthetic implant, and the physical performance for which the particular metallic implants was initially chosen [47]. appropriate host reaction throughout its designed clinical utilization in a body system. The interaction between host tissue, the performance of the metallic implant, and its material characteristics regulate the biocompatibility of an implant, as demonstrated in Figure 3 [47]. The biological reaction of this kind of implant might alter with any specific post-implantation modifications in the host tissue. These biological reactions rely on the chemical and physical characteristics of an implant, the kinds and regions of host tissues that are subjected to an implant, the length of the exposure, the implant's surface characteristics, structure, and forces employed on synthetic implant, and the physical performance for which the particular metallic implants was initially chosen [47]. Despite the fact that Mg-based bioalloys have considerable properties, it is still required to enhance the mechanical characteristics to maintain their strength throughout the incubation period. Magnesium possesses a hexagonal close packed (HCP) structure, which has a restricted number of slip systems and, for that reason, presents a brittle behavior. This is essential to increasing the ductility of Mg materials with little or no effect on strength. Therefore, nanocomposites may boost the strength and ductility at the same time [45]. The appropriate option for reinforcements, their grain size, and their natural biocompatible characteristics can achieve the greatest degree of mechanical and anticorrosion properties and a great cell response. The composite materials consist of a minimum of two materials, which are known as the matrix and reinforcement. All the materials of the composite ought to be cytocompatible and not induce toxicity in any SBF solution. The composite material permits the mixture of the matrix and reinforcement properties including great mechanical characteristics (compressive strength (CS) and tensile strength (TS)), high anticorrosion performance, and biocompatibility. The choice of matrix component and reinforcement component is extremely vital to attain the desirable characteristics [45].
Experts have employed new ideas to enhance the mechanical properties, corrosion performance, and biocompatibility of these materials, which are extensively reviewed due to the stability of Mg-based materials in the biomedical area. Carbon-based materials display a broad variety of distinctive characteristics, such as a great aspect ratio, an outstanding high Young's Despite the fact that Mg-based bioalloys have considerable properties, it is still required to enhance the mechanical characteristics to maintain their strength throughout the incubation period. Magnesium possesses a hexagonal close packed (HCP) structure, which has a restricted number of slip systems and, for that reason, presents a brittle behavior. This is essential to increasing the ductility of Mg materials with little or no effect on strength. Therefore, nanocomposites may boost the strength and ductility at the same time [45]. The appropriate option for reinforcements, their grain size, and their natural biocompatible characteristics can achieve the greatest degree of mechanical and anticorrosion properties and a great cell response. The composite materials consist of a minimum of two materials, which are known as the matrix and reinforcement. All the materials of the composite ought to be cytocompatible and not induce toxicity in any SBF solution. The composite material permits the mixture of the matrix and reinforcement properties including great mechanical characteristics (compressive strength (CS) and tensile strength (TS)), high anticorrosion performance, and biocompatibility. The choice of matrix component and reinforcement component is extremely vital to attain the desirable characteristics [45].
Experts have employed new ideas to enhance the mechanical properties, corrosion performance, and biocompatibility of these materials, which are extensively reviewed due to the stability of Mg-based materials in the biomedical area. Carbon-based materials display a broad variety of distinctive characteristics, such as a great aspect ratio, an outstanding high Young's modulus and strength, as well as remarkable electrical and thermal characteristics. These outstanding properties have resulted in the employment of carbonaceous nanomaterials as the reinforcements for polymers, ceramics, and MMC for their distinctive characteristics [27]. The characteristics of GFN-associated components and their capabilities to be functionalized and coupled with biomolecules and materials provide numerous possibilities to offer biocomposites with tailored characteristics, as presented in Figure 4.
Metals 2020, 10, 1002 6 of 40 modulus and strength, as well as remarkable electrical and thermal characteristics. These outstanding properties have resulted in the employment of carbonaceous nanomaterials as the reinforcements for polymers, ceramics, and MMC for their distinctive characteristics [27]. The characteristics of GFN-associated components and their capabilities to be functionalized and coupled with biomolecules and materials provide numerous possibilities to offer biocomposites with tailored characteristics, as presented in Figure 4.

Graphene Family Nanomaterials
Despite the fact that composite materials can offer a number of positive aspects that single-component materials cannot, they could possibly likewise offer features that need more enhancements. As an illustration, ceramic-polymeric composites might be bioactive, whereas they could result in sensitive responses and offer minimal mechanical characteristics [48]. Even with the latest developments, the progress of novel materials and approaches to produce the new class of biocomposites with enhanced features is being given great attention [49]. Metals are employed for a number of biomedical purposes in neat form or as alloys because of their great toughness and stiffness. The Gr-family components might enhance the characteristics of metals even more and present a bioactive character to the metal-based composites.
As a new nanomaterial family, GFNs demonstrate outstanding capabilities against a wide range of bacteria including Gram-positive and -negative bacteria [31]. Single-GFN and GFN-based composites exhibit obvious antibacterial functionality. Furthermore, the reasonable design of GFN-based composites might improve this particular potential. A comprehensive overview of single-GFNs' antibacterial functionality is presented in Table 1. The antibacterial activity of Gr was first documented in 2010 [50,51], where graphene was observed to significantly destroy and cause the dysfunction of the bacteria attaching to it [51]. This antibacterial approach was effective and fast for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and destruction was observed to primarily take place in the cell membrane. A test disclosed that graphene nanosheets actually possessed a greater antibacterial activity in comparison with conventional antibiotics, including kanamycin [52]. Similar to Gr, GO also exhibits an outstanding bactericidal capability for a wide

Graphene Family Nanomaterials
Despite the fact that composite materials can offer a number of positive aspects that single-component materials cannot, they could possibly likewise offer features that need more enhancements. As an illustration, ceramic-polymeric composites might be bioactive, whereas they could result in sensitive responses and offer minimal mechanical characteristics [48]. Even with the latest developments, the progress of novel materials and approaches to produce the new class of biocomposites with enhanced features is being given great attention [49]. Metals are employed for a number of biomedical purposes in neat form or as alloys because of their great toughness and stiffness. The Gr-family components might enhance the characteristics of metals even more and present a bioactive character to the metal-based composites.
As a new nanomaterial family, GFNs demonstrate outstanding capabilities against a wide range of bacteria including Gram-positive and -negative bacteria [31]. Single-GFN and GFN-based composites exhibit obvious antibacterial functionality. Furthermore, the reasonable design of GFN-based composites might improve this particular potential. A comprehensive overview of single-GFNs' antibacterial functionality is presented in Table 1. The antibacterial activity of Gr was first documented in 2010 [50,51], where graphene was observed to significantly destroy and cause the dysfunction of the bacteria attaching to it [51]. This antibacterial approach was effective and fast for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and destruction was observed to primarily take place in Metals 2020, 10, 1002 7 of 41 the cell membrane. A test disclosed that graphene nanosheets actually possessed a greater antibacterial activity in comparison with conventional antibiotics, including kanamycin [52]. Similar to Gr, GO also exhibits an outstanding bactericidal capability for a wide range of bacteria [51]. Gr is a plane of carbon atoms, and GO is an oxidized Gr sheet with numerous oxygen-containing FGs [53]. Right after reducing the functional oxygen-containing groups, GO will certainly turn out to be rGO. Commonly, rGO nanosheets tend to be reduced through hydrazine [51] and dithiothreitol [54]. Bacteria were suggested to reduce GO by means of the metabolism of glycolysis in a self-limiting fashion [55]. Neat Gr spread out with complications in the solutions (aqueous and organic) as a result of the insufficient hydrophilic groups. On the other side, GO and rGO demonstrate a particular amphiphilicity (lipophilic and certainly hydrophilic) because of the amount of extra FGs [31]. Gr is another appealing and distinctive crystalline allotrope of carbon that demonstrates 2D properties. It is regarded as the initial 2D material [61,62]. In this regard, Figure 5 exhibits the historical background and development stages of Gr formation [49]. Gr was identified in 2004 by Geim and Novoselov [62]. They effectively separated graphene through mechanical exfoliation of graphite crystals employing the cohesive tape approach. Their breakthrough was recently privileged with the 2010 Nobel Prize in Physics. Nevertheless, the low efficiency of this particular approach causes it to be inappropriate for large-scale manufacturing purposes. The essential advancements in relation to GFNs, in particular Gr, are described pictorially in Figure 5. Gr might be generated by four approaches: (1) CVD [63]; this research that commenced in the 1970s was accompanied by a considerable amount of studies conducted by surface researchers on monolayer graphite [64]; (2) epitaxial growth of the Gr layer by electrically insulating substrates [65]; (3) mechanical exfoliation of Gr from bulk graphite (e.g., using Scotch tape); and (4) reduction of graphene derivatives including GO [66,67]. The latter approach exhibits possibilities pertaining to the manufacturing of graphene sheets in the mass amounts that are required for applying it to composites. GO sheets might be taken out of "graphite oxide (GRO)", which is commonly prepared through the oxidation of graphite [68,69]. GRO could be entirely exfoliated to create an aqueous solution of GO sheets by sonication [61]. Extensive investigation [70] on these kinds of aqueous solutions was performed in the 1950s and the 1960s. Chemical reduction of GO in colloidal suspensions might be conducted to fabricate massive volumes of chemically modified graphene (CMG) sheets [61,71], which are appropriate for compositing purposes. Thermal reduction of GRO is a different method that is usually employed to attain massive volumes of Gr platelets. Fast heating (> 2000 • C/min) up to 1050 • C exfoliates, as well as reduces GRO [61,72,73]. However, GO and rGO are usually manufactured through relatively inexpensive chemical approaches employing graphite as the basis material [74][75][76][77]. They are usually distributed evenly in stable aqueous solutions to construct macroscopic structures at commercial-scale [76,78]. fabricate massive volumes of chemically modified graphene (CMG) sheets [61,71], which are appropriate for compositing purposes. Thermal reduction of GRO is a different method that is usually employed to attain massive volumes of Gr platelets. Fast heating (> 2000 °C/min) up to 1050 °C exfoliates, as well as reduces GRO [61,72,73]. However, GO and rGO are usually manufactured through relatively inexpensive chemical approaches employing graphite as the basis material [74][75][76][77]. They are usually distributed evenly in stable aqueous solutions to construct macroscopic structures at commercial-scale [76,78]. Gr also offers a fracture strength of 130 GPa, a Young's modulus of 1 TPa, a low density of 1 g/cm 3 , and a great specific surface area that might enable it to be a remarkable reinforcement intended for MMC [79,80]. The reason behind the great stiffness and elastic strength is the Sp 2 hybridized and covalently bonded C-atoms in a hexagonal network. Furthermore, graphene might experience substantial elastic strains up to 15% [81]. The issues including insufficient bonding at the Gr/metal interface lead to the poor interface adhesion and decrease the mechanical characteristic of the metal matrix resulting from the elastic incompatibility [82,83]. Moreover, Gr has more difficulty in spreading out in comparison with other reinforcements, as a result of its interfacial contact region [83]. The maintenance of the integrated structure of GNPs is the essential matter due to the fact the more complete the structure of the GNPs is, the greater and considerably more productive the bearing potential of GNPs might be in the matrix throughout a loading procedure. Thus, composites might attain greater strength and modulus and considerably more issues in elastic deformation [84].

Fabrication of Graphene-Mg MMNCs
Magnesium MMCs present versatile mechanical and anticorrosion characteristics as obtained via the choice of the range of the reinforcement phase. The amount, dispersion, and size of the reinforcements are key elements regarding the mechanical performance and degradation rate of Mg MMCs. Numerous reinforcements were used to fabricate Mg MMCs, including Ca-P-and bioglass (BG)-based ceramic [85][86][87][88], ZnO [25], and Ca particles [89], by means of powder metallurgy (PM) and stir casting (SC) methods. In this context, it was suggested that the uniform distribution of GNPs in the metal matrix is a crucial issue throughout the fabrication of composites. The thickness of GNPs with joint stacked sheets is hence considerably greater in comparison with an individual graphene sheet. GNPs are usually effortlessly dispersed in any kind of solvent and matrix. The Mg-GFs Gr also offers a fracture strength of 130 GPa, a Young's modulus of 1 TPa, a low density of 1 g/cm 3 , and a great specific surface area that might enable it to be a remarkable reinforcement intended for MMC [79,80]. The reason behind the great stiffness and elastic strength is the Sp 2 hybridized and covalently bonded C-atoms in a hexagonal network. Furthermore, graphene might experience substantial elastic strains up to 15% [81]. The issues including insufficient bonding at the Gr/metal interface lead to the poor interface adhesion and decrease the mechanical characteristic of the metal matrix resulting from the elastic incompatibility [82,83]. Moreover, Gr has more difficulty in spreading out in comparison with other reinforcements, as a result of its interfacial contact region [83]. The maintenance of the integrated structure of GNPs is the essential matter due to the fact the more complete the structure of the GNPs is, the greater and considerably more productive the bearing potential of GNPs might be in the matrix throughout a loading procedure. Thus, composites might attain greater strength and modulus and considerably more issues in elastic deformation [84].

Fabrication of Graphene-Mg MMNCs
Magnesium MMCs present versatile mechanical and anticorrosion characteristics as obtained via the choice of the range of the reinforcement phase. The amount, dispersion, and size of the reinforcements are key elements regarding the mechanical performance and degradation rate of Mg MMCs. Numerous reinforcements were used to fabricate Mg MMCs, including Ca-P-and bioglass (BG)-based ceramic [85][86][87][88], ZnO [25], and Ca particles [89], by means of powder metallurgy (PM) and stir casting (SC) methods. In this context, it was suggested that the uniform distribution of GNPs in the metal matrix is a crucial issue throughout the fabrication of composites. The thickness of GNPs with joint stacked sheets is hence considerably greater in comparison with an individual graphene sheet. GNPs are usually effortlessly dispersed in any kind of solvent and matrix. The Mg-GFs nanocomposite is usually manufactured through employing various manufacturing approaches including disintegrated melt deposition (DMD), stir casting, liquid infiltration, gravity casting, melting, PM, and semi-powder metallurgy (SPM). Nevertheless, current research reveals that PM coupled with the hot extrusion (HTE) procedure and SPM is one of the successful approaches to achieve the appropriate mechanical characteristics. Traditional manufacturing approaches, for example stir casting, are not able to address this issue [83].

Powder Metallurgy
The PM approach is an adaptable method for fabrication of Mg-based composites with GFN nanofillers because of its ease of use, overall flexibility, and close proximity to net-shaped functionality, as shown in Figure 6. The procedure consists of mechanical mixing of nanofillers with metal/alloy powders in a rotary mill, accompanied by sintering and various types of densification approaches including cold isostatic pressing (CIP), hot pressing/hot isostatic pressing (HP/HIP), or spark plasma sintering (SPS). In particular circumstances, extra mechanical deformation modifications including HTE, HF (hot forging), hot rolling (HR), friction stir processing (FSP), and equal channel angular processing (ECA) approaches are employed to additionally compact them into full-compact nanocomposite specimens. With the PM approach, which consists of three fundamental stages (blending, densification, and sintering), a homogeneous and even distribution of reinforcing agents within the matrix alloy has been accomplished [90,91]. The HTE procedure is applied to enhance the densification of composites due to the fact that it is complicated to avoid the creation of micropores in the composite following sintering [92,93]. This review article describes the current trends in processing and the mechanical and anticorrosion characteristics of Mg-based alloys incorporated with Gr-family nanomaterials.
The accomplishment of a uniform additive phase via simply blending metal powders with carbon-based components is fairly inadequate, as anticipated. By utilizing a ball mill or mechanical alloying (MA) approaches, a greater distribution of additive agents is usually obtained. Nevertheless, the handling methods must be done with care in order to maintain the structural integrity of carbon-based components. This is due to the fact that the long-term ball milling procedure might damage the crystallinity of carbon-based components [27]. A number of authors used a traditional mixed press-sinter method to fabricate the MMCs. Incorporation of Gr-family nanomaterials into Mg matrix improves the thermal conductivity, and GNPs are likewise great additive agents for strengthening the mechanical performance of the Mg composite. Furthermore, Mg is generally defined as a light metal; it is typical used in the vehicle and aviation industrial sectors to be able to lessen fuel usage. Thus, the manufacturing and advancement of Mg-GNP composites are extremely crucial. Shahin et al. [94] employed MA methods to spread out 0.5 wt.% and 0.1 wt.% Zr and GNPs, respectively, in the Mg matrix. The blend's powder was subsequently cold pressed and sintered at 760 MPa and 610 • C respectively to obtain the nanocomposite. Their outcome revealed that the Mg and Zr powders showed an irregular flake-like shape, even though Gr powders presented a flake-like shape along with wrinkled edges and a particle size of 15 µm. which consists of three fundamental stages (blending, densification, and sintering), a homogeneous and even distribution of reinforcing agents within the matrix alloy has been accomplished [90,91]. The HTE procedure is applied to enhance the densification of composites due to the fact that it is complicated to avoid the creation of micropores in the composite following sintering [92,93]. This review article describes the current trends in processing and the mechanical and anticorrosion characteristics of Mg-based alloys incorporated with Gr-family nanomaterials.

Stirring Casting
PM approaches are quite costly and might lead to the destruction of additive phases throughout the ball milling procedure, which will ultimately have an effect on the mechanical characteristics of the produced composites. On the other side, the stir casting approach is desirable because of numerous benefits compared to the PM approach. For instance, the stir casting approach is more affordable, and porosity forms as a result of the solidification shrinkage, while hydrogen generation is extremely low. In addition, a broad range of patterns and sizes (of matrix and additive phases) can certainly be employed. The additive phases do not cause any damage, and virtually any type of matrix/reinforcement is usually applied regardless of the melting points [95]. An additional method for MMCs' advancement is to embed the additive phases into the melt accompanied by the stirring casting approach. Typically, bioceramic or BG is chosen to be the additive phases; however, the weak wettability of the bioceramic restricts the content of additive phases, besides the distribution of the additive phases. A number of approaches has already been performed to overcome this restriction of the SC approach. Du et al. [92] evaluated the strengthening mechanism of Mg (ZK60)-GNP composites fabricated via melting stirring accompanied by the HTE procedure. Homogeneous dispersion of GNPs in the ZK60 matrix was obtained via a melting mixture approach. Moreover, GNP embedding in ZK60 matrix led to increasing both the tensile and compressive strength. Overall, the PM method following the HTE procedure leads to enhancement of the mechanical characteristics of MMCs. In contrast to PM MMCs, which possess a lower than 0.5% porosity because of the HTE procedure, the semi-solid cast composite was observed to be microporous, hence suggesting a higher degradation rate in comparison with the PM coupled with HTE procedure [96]. In this context, Ramezanzade et al. [96] prepared Mg-based composites by embedding various contents of GNPs (0.1, 0.2, and 0.4 wt.%) as additive agents via an SC method accompanied by homogenization and extrusion in an effort to strengthen the mechanical characteristics of the Mg-based alloy. Their outcome showed that embedding 0.2 wt.% GNPs into the Mg-based alloy resulted in grain refinement (36%) and the lessening of anisotropy (14%), as well as a reduction of twin formation. The homogeneous distribution of GNPs accompanied by enhanced non-basal slip and grain refinement enhanced the tensile fracture strain.

Disintegrated Melt Deposition
Materials researchers have invested substantial effort by presenting enhanced melt procedures to be able to accomplish a greater distribution of GNPs in the metal matrix. Wang et al. [97][98][99] and Rashad et al. [95,100] systematically examined the manufacturing process and mechanical performance of Mg-based composites incorporated with Gr. The DMD approach was implemented to distribute nano-additives in molten Mg alloys [27], as shown in Figure 7. This approach consists of mechanical stirring Mg chips and the nano-additive under a neutral gas (e.g., argon) to cast ingots with the subsequent HTE procedure. Microstructural assessment showed that the extruded composite specimens presented a relatively even dispersion of Gr-family nanomaterials [27]. mechanical stirring Mg chips and the nano-additive under a neutral gas (e.g., argon) to cast ingots with the subsequent HTE procedure. Microstructural assessment showed that the extruded composite specimens presented a relatively even dispersion of Gr-family nanomaterials [27]. Rashad et al. [95] also fabricated Mg alloy-GNP composite via the DMD approach accompanied by homogenization treatment and the subsequent HTE procedure, and their outcomes showed that GNP incorporation had a considerable influence on reducing the grain size and modifying the basal textures because of their homogeneous distribution within the matrix of the Mg-based composite, which led to substantial enhancement of the mechanical properties including the hardness, TS, and CS. Aside from that, the TS of an extruded Mg alloy-GNP composite was also evaluated at higher temperatures, and their result showed that fracture strain increased and TS diminished with increasing testing temperature. The increase of fracture strain at elevated temperature was primarily caused by substantial grain refinement and homogeneous nano-additive dispersion. The fracture surface evaluation showed that deformation potentially took place via grain boundary (GB) moving accommodated via penetration transport. Wang et al. [99] also uniformly dispersed GNPs in the matrix of bare Mg in a dynamic solidification approach. In this approach, via the pre-dispersion procedure, incorporated GNPs split up the agglomerate particles of neat GNPs and maintained the GNPs in a repulsive situation. This type of distribution resulted in further reducing the grain size and more enhancements of the mechanical properties. Rashad et al. [95] also fabricated Mg alloy-GNP composite via the DMD approach accompanied by homogenization treatment and the subsequent HTE procedure, and their outcomes showed that GNP incorporation had a considerable influence on reducing the grain size and modifying the basal textures because of their homogeneous distribution within the matrix of the Mg-based composite, which led to substantial enhancement of the mechanical properties including the hardness, TS, and CS. Aside from that, the TS of an extruded Mg alloy-GNP composite was also evaluated at higher temperatures, and their result showed that fracture strain increased and TS diminished with increasing testing temperature. The increase of fracture strain at elevated temperature was primarily caused by substantial grain refinement and homogeneous nano-additive dispersion. The fracture surface evaluation showed that deformation potentially took place via grain boundary (GB) moving accommodated via penetration transport. Wang et al. [99] also uniformly dispersed GNPs in the matrix of bare Mg in a dynamic solidification approach. In this approach, via the pre-dispersion procedure, incorporated GNPs split up the agglomerate particles of neat GNPs and maintained the GNPs in a repulsive situation.

Friction Stir Processing
This type of distribution resulted in further reducing the grain size and more enhancements of the mechanical properties.

Friction Stir Processing
FSP is established by the alteration of friction stir welding (FSW) to create a composite with a sub-microstructure close to the surface area of metallic materials via dynamic recrystallization, as demonstrated in Figure 8 [90]. In this approach, a spinning device pin is introduced to the substrate in a way that the friction and plastic deformation caused by the device heat and soften the workpiece. The device pin subsequently stimulates the intermixing of the material in a local area [27]. To manufacture GFN-reinforced composites, numerous holes are initially drilled into a metallic plate accompanied by filling up with GFNs and modifying with subsequent FSP (Figure 8). Arab et al. [101] manufactured a nanocomposite that was prepared via embedding GNPs into AZ31 magnesium alloy via FSP. Traditional FSP samples confirmed a 133% increase in strain-to-fracture, even though it was diminished by incorporating GNPs. Nevertheless, the existence of GNPs elevated the YS and UTS to 217 and 278 MPa, respectively. Chen et al. [17] also successfully fabricated Mg-GNP composite via liquid state approaches followed by solid state stirring. Their approach is schematically revealed in Figure 8. In this procedure, GNPs are incorporated into the molten magnesium via a feeding procedure and subsequently distributed into the molten composite via an ultrasonic procedure for a short time. Microstructural evaluation results revealed that GNPs were not evenly distributed within the Mg-based matrix. To obtain an enhanced distribution of GNPs in the composite, FSP was employed on the surface of the cast specimens. In this regard, FSP led to enhancement of the distribution of GNPs in the matrix of the composite.  Figure 8. In this procedure, GNPs are incorporated into the molten magnesium via a feeding procedure and subsequently distributed into the molten composite via an ultrasonic procedure for a short time. Microstructural evaluation results revealed that GNPs were not evenly distributed within the Mg-based matrix. To obtain an enhanced distribution of GNPs in the composite, FSP was employed on the surface of the cast specimens. In this regard, FSP led to enhancement of the distribution of GNPs in the matrix of the composite.

Selective Laser Melting
The laser deposition approach pertains to utilizing coherent and extreme laser beams for fabricating MMNCs employing metal powders. Laser beams usually have the ability of achieving extremely high-speed rates of surface melting accompanied by solidification at cooling rates of ∼107

Selective Laser Melting
The laser deposition approach pertains to utilizing coherent and extreme laser beams for fabricating MMNCs employing metal powders. Laser beams usually have the ability of achieving extremely high-speed rates of surface melting accompanied by solidification at cooling rates of ∼107 ks −1 . The laser processing approach provides unique benefits regarding creating composites including a short handling period, a reduced amount of distortion of the specimen, and near net shape manufacturing. As shown in Figure 9, SLM was employed by Shuai et al. [102] to also prepare 3D honeycomb nanostructure-embedded Mg alloys, in which the honeycomb nanostructure was reinforced with GO as an additive phase. Results revealed that GO was dispersed within the GBs and progressively wrapped α-Mg grains when the content of GO increased. The close and complete wrapping suggested a beneficial affinity and useful protection of GFNs, for instance GO in Mg-based alloys, against corrosion attack.

Multi-Step Dispersion Route
Melt stirring is a traditional method for MMC fabrication, while the direct encapsulation of GFNs like Gr (additive phase) into the melt could effortlessly result in carbon float and aggregation because of the layered structure of Gr [100]. To disperse the GNPs effectively into the metals' matrix, the multi-step dispersion route combining different process steps was developed. Xiang et al. [83] encapsulated Mg-based composites with GNPs by employing the multi-step dispersion method comprising pre-dispersion of the additive phase, semi-solid treatment stirring (SSTS), and high energy ultrasonic processing, followed by the HTE procedure, as shown in Figure 10

Multi-Step Dispersion Route
Melt stirring is a traditional method for MMC fabrication, while the direct encapsulation of GFNs like Gr (additive phase) into the melt could effortlessly result in carbon float and aggregation because of the layered structure of Gr [100]. To disperse the GNPs effectively into the metals' matrix, the multi-step dispersion route combining different process steps was developed. Xiang et al. [83] encapsulated Mg-based composites with GNPs by employing the multi-step dispersion method comprising pre-dispersion of the additive phase, semi-solid treatment stirring (SSTS), and high energy ultrasonic processing, followed by the HTE procedure, as shown in Figure 10

Semi-Powder Metallurgy
Rashad et al. [91] performed Mg-GNP composite synthesis by employing the SPM approach. They noticed that the Mg structure was modified because the encapsulation of GNPs had an effect on the mechanical performance of the composite. Turan and coworkers [105][106][107][108][109] likewise investigated the influences of carbon-based additives on the microstructure and properties of Mg-based composites by this approach. The SPM approach provides a homogeneous dispersion of the additive phase in the Mg matrix alloy. This method is free of ball milling since ball milling is regarded as a major issue when employing Mg due to the fact that it generates heat, which might burn the Mg powder readily, as exhibited in Figure 11 [110]. Thus, this approach is used as an alternate choice to ball milling, and it has good possibilities regarding the fabrication of a Mg-based composite, which is regarded as a great candidate for engineering purposes. GNPs are usually distributed in almost all types of solvents and matrices effortlessly in comparison to CNTs. The Mg alloy-GNP composite is manufactured by the semi-powder metallurgy method accompanied by the HTE procedure. Their result exposed the homogeneous distribution of GNPs in the matrix [109]. In this regard, Sabri et al. [110] also synthesized a Mg-based composite by SPM, which was encapsulated within GNPs, and their result revealed that homogeneous and even dispersing of the low amount of GNPs inside the Mg-based matrix led to partial agglomeration of GNPs with better mechanical properties. In the same manner, Rashed et al. [111] utilized a simple approach to enhance the mechanical properties of Mg-GNP composites by intercalating a small amount of MWCNTs among the layers of GNPs. Their outcome demonstrated that that reduction of the grain size did not occur homogeneously within the matrix surface. This could be caused by the weak distribution of 2D GNPs as an additive phase in the matrix. In this view, the microstructure of Mg alloy-CNTs composite shows the presence of micropores on its surface, whereas Mg alloy/CNTs-GNPs are free of micropores and present great chemical bonding among the additive phase and the matrix. Their

Semi-Powder Metallurgy
Rashad et al. [91] performed Mg-GNP composite synthesis by employing the SPM approach. They noticed that the Mg structure was modified because the encapsulation of GNPs had an effect on the mechanical performance of the composite. Turan and coworkers [105][106][107][108][109] likewise investigated the influences of carbon-based additives on the microstructure and properties of Mg-based composites by this approach. The SPM approach provides a homogeneous dispersion of the additive phase in the Mg matrix alloy. This method is free of ball milling since ball milling is regarded as a major issue when employing Mg due to the fact that it generates heat, which might burn the Mg powder readily, as exhibited in Figure 11 [110]. Thus, this approach is used as an alternate choice to ball milling, and it has good possibilities regarding the fabrication of a Mg-based composite, which is regarded as a great candidate for engineering purposes. GNPs are usually distributed in almost all types of solvents and matrices effortlessly in comparison to CNTs. The Mg alloy-GNP composite is manufactured by the semi-powder metallurgy method accompanied by the HTE procedure. Their result exposed the homogeneous distribution of GNPs in the matrix [109]. In this regard, Sabri et al. [110] also synthesized a Mg-based composite by SPM, which was encapsulated within GNPs, and their result revealed that homogeneous and even dispersing of the low amount of GNPs inside the Mg-based matrix led to partial agglomeration of GNPs with better mechanical properties. In the same manner, Rashed et al. [111] utilized a simple approach to enhance the mechanical properties of Mg-GNP composites by intercalating a small amount of MWCNTs among the layers of GNPs. Their outcome demonstrated that that reduction of the grain size did not occur homogeneously within the matrix surface. This could be caused by the weak distribution of 2D GNPs as an additive phase in the matrix. In this view, the microstructure of Mg alloy-CNTs composite shows the presence of micropores on its surface, whereas Mg alloy/CNTs-GNPs are free of micropores and present great chemical bonding among the additive phase and the matrix. Their outcome likewise confirmed that GNPs as part of GFNs are encapsulated in Mg matrix with outstanding interfacial adhesion without the presence of cracks.

Mechanical Properties of Mg-GNP-Based Composites
The considerable enhancement of the mechanical performance of the Mg-based composite was basically caused by decreasing grain size and close interfacial bonding of GFNs within the matrix. In particular, the wrinkled surface of Gr-family materials like GNPs might result in successful mechanical interlocking with the composite matrix [112]. When a crack grows around the GNPs, the stress in the matrix might be properly shifted to GNPs as a result of the superior elastic modulus of GNPs in comparison with other bioactive ceramics. During this period, GNPs are lengthened and fractured or possibly pulled out through the matrix when going above the greatest interface bonding strength; the mechanisms of pull-out impact, crack bridging, deviation in the path of crack growth, and crack tip blunting via GNPs absorb a great amount of outward energy, although keeping a small amount of energy for additional growth of the crack, as shown in Figure 12. Consequently, the crack grows in a step-like fashion and progressively reduces or possibly ends, in that way enhancing the load-bearing ability of the matrix [32].
There are widely recognized toughening systems for the Mg matrix. These mechanisms are refined grain structure, Orowan looping, solid solution strengthening, precipitation strengthening, stress transfer or load bearing, the coefficient of thermal expansion (CTE), and modulus mismatch toughening [113]. Nevertheless, a uniform dispersion of GNPs within the Mg matrix is not virtually attainable. Moreover, to be able to obtain stress transfer through Mg matrix to GNPs, we require a solid attaching mechanism of graphene to metal [84]. Due to the fact GNPs are a 2D material, the stress transfer toughening system might be among the primary strengthening mechanisms in the Mg matrix strengthened by GNPs [114][115][116][117][118][119][120]. The stress that often is employed on the Mg matrix could transfer to the additive phases (GFNs) from the Mg matrix via shear stresses combined with the interface among the Mg matrix and additive phases.
Due to the fabrication technique, the grain size of the Mg matrix reduces. Because of the refined grain structure of the Mg matrix, which leads to enhancement of the strength of the Mg-based composite based on the Hall-Petch formula [92,97,98,113], it is among the primary strengthening systems in the Mg matrix strengthened via GFNs. Aside from that, due to the strain hardening, Figure 11. Schematic representation of Semi powder metallurgy (SPM) for synthesis of GNPs reinforced Mg-based composite, reproduced from [110], with permission from Elsevier, 2020.

Mechanical Properties of Mg-GNP-Based Composites
The considerable enhancement of the mechanical performance of the Mg-based composite was basically caused by decreasing grain size and close interfacial bonding of GFNs within the matrix. In particular, the wrinkled surface of Gr-family materials like GNPs might result in successful mechanical interlocking with the composite matrix [112]. When a crack grows around the GNPs, the stress in the matrix might be properly shifted to GNPs as a result of the superior elastic modulus of GNPs in comparison with other bioactive ceramics. During this period, GNPs are lengthened and fractured or possibly pulled out through the matrix when going above the greatest interface bonding strength; the mechanisms of pull-out impact, crack bridging, deviation in the path of crack growth, and crack tip blunting via GNPs absorb a great amount of outward energy, although keeping a small amount of energy for additional growth of the crack, as shown in Figure 12. Consequently, the crack grows in a step-like fashion and progressively reduces or possibly ends, in that way enhancing the load-bearing ability of the matrix [32].
There are widely recognized toughening systems for the Mg matrix. These mechanisms are refined grain structure, Orowan looping, solid solution strengthening, precipitation strengthening, stress transfer or load bearing, the coefficient of thermal expansion (CTE), and modulus mismatch toughening [113]. Nevertheless, a uniform dispersion of GNPs within the Mg matrix is not virtually attainable. Moreover, to be able to obtain stress transfer through Mg matrix to GNPs, we require a solid attaching mechanism of graphene to metal [84]. Due to the fact GNPs are a 2D material, the stress transfer toughening system might be among the primary strengthening mechanisms in the Mg matrix strengthened by GNPs [114][115][116][117][118][119][120]. The stress that often is employed on the Mg matrix could transfer to the additive phases (GFNs) from the Mg matrix via shear stresses combined with the interface among the Mg matrix and additive phases.  Due to the fabrication technique, the grain size of the Mg matrix reduces. Because of the refined grain structure of the Mg matrix, which leads to enhancement of the strength of the Mg-based composite based on the Hall-Petch formula [92,97,98,113], it is among the primary strengthening systems in the Mg matrix strengthened via GFNs. Aside from that, due to the strain hardening, increasing dislocation amount, and CTE mismatch toughening amplified in the Mg-based composites, this likewise leads to toughening of the Mg matrix strengthened via GNPs [30,90,114,115]. It is worth mentioning that CTE mismatch among the Mg matrix and Gr may result in enhancing the dislocation amounts and increasing the toughness of the Mg-based composites [30,93,116,117]. The CTE mismatch toughening systems in the Mg matrix strengthened by GFNs are determined by the size, morphology, and geometry of the Mg matrix and additive phases. Another toughening system in the Mg matrix strengthened by GNPs is Orowan looping, which was suggested by Rashad et. al. [118,119], where unmodified particles are positioned inside the grains. Hence, the size of grains and additive phases are extremely crucial to obtain the Orowan toughening in the Mg matrix. Residual dislocation loops could be created close to GNPs following a dislocation that bows out and bypasses all of them. Substantial work hardening is usually ordered through these loops [101,120].
Munir et al. [30] examined a Mg-based matrix strengthened with GNPs that were prepared via PM for biomedical purposes. GNPs (5-9 nm layer thicknesses) with various amounts (0.1-0.3 wt.%) were distributed within the Mg-based matrix via the ball milling method. The outcomes revealed that GNPs' incorporation enhanced the mechanical characteristics of Mg through thermal mismatch and reducing the grain size. Furthermore, maintaining the structural integrity of GNPs throughout the procedure enhanced the mechanical and corrosion properties of the Mg-GNP composites. Their research illustrated that Mg-xGNPs with x < 0.3 wt.% may present potential biodegradable materials for implant applications. Moreover, more incorporation of GNPs, up to a specific amount, increased the mechanical properties of metal matrices including hardness and YS [121][122][123]. Nevertheless, throughout the composite fabrication procedure, structural modifications in dispersed GFNs take place such as re-agglomeration, with the following buildup of defects because of their connection with nearby GNPs in the agglomerate through friction and impact, which leads to the constantly changing mechanical and general performance of the Mg-based matrix [30]. A Mg-GNP composite was prepared via the SPM technique by Rashad et al. [91], and their results exhibited that GNP were actually dispersed uniformly in the Mg matrix and, for this reason, worked as a successful reinforcing phase to protect against further deformation. The enhancements in elongation (EL), YS 0.2% , UTS, and Vickers HR were significantly higher for the Mg-0.3GNP composite in comparison with bare Mg. Rashad et al. [119] synthesized a Mg-1Cu-xGNP composite via the SPM technique, and their result showed that composite specimens presented higher mechanical strength compared to the bare Mg. The superior strength of the composites might be caused by fundamental strengthening systems, such as CTE and EL mismatch, Orowan toughening, and stress transfer. In this context, Saberi et al. [110] synthesized a Mg-based-GNP composite through the SPM technique with various concentrations of GNPs. Their result presented that strong interfacial bonding was found between GNPs and the Mg-based alloy owing to the presence of residual oxygen in GNPs. Likewise, Yuan et al. [116] further confirmed that the existence of residual oxygen in GNPs had a critical role in increasing the interfacial bonding between the Mg matrix and reinforcement agent (GNPs). This great interfacial bonding resulted in increasing the mechanical characteristics including yield strength and elongation and the prevention of the occurrence of cavities at the Mg-Gr interface of the matrix and reinforcement agent (GNPs). This enhancement of the mechanical characteristics due to the presence of residual oxygen in GNPs was also found by Chen [90], Rashad [124], and Xiang et al. [83]. In another study, a Mg matrix encapsulated within 0.3 wt.% graphene via SSIT with the subsequent HTE procedure was demonstrated by Yang et al. [93]. Their result showed that the structure of the composite had been obviously refined after the HTE procedure, which resulted in the enhancement of the mechanical properties. The other reason for such strength improvement was related to the homogenous distribution of graphene and great interfacial bonding. The effect on the graphene family nanomaterials (GFNs) on the strength and ductility of the Mg-based alloy/composite is summarized in Table 2.

Biocorrosion and Biodegradability of Mg-GFNs-Based Composites
The entire biomaterial should make it through a certain healing period for 12-18 weeks [14,[125][126][127][128]. All examinations regarding Mg-based alloys have demonstrated high degradation, where the Mg alloys are fully absorbed prior to the least healing duration of 12 weeks [129], which results in H 2 gas release, inducing cavities, reduced mechanical integrity, regional swelling, and discomfort for the patient [130][131][132]. To address this restriction, Mg-based composites that were recently fabricated intended for implant applications should possess corrosion rates lower than 0.5 mm/year in physiological fluids at 37 • C [133]. The corrosion mechanism can be understood by analyzing the corroded surfaces of Mg-based specimens when exposed to the SBF. As can be seen in Figure 13, Mg-based specimens react with the SBF along with H 2 generation. The general corrosion reaction of Mg in physiological media is presented below [134]: corroded surfaces of Mg-based specimens when exposed to the SBF. As can be seen in Figure 13, Mg-based specimens react with the SBF along with H2 generation. The general corrosion reaction of Mg in physiological media is presented below [134]: Based on the previously mentioned reactions, Mg(OH)2 is created on the Mg alloy surface. The chloride ion is considered to have an adverse effect on the corrosion resistance of Mg. Numerous investigations have verified that a high chloride amount is facilitated by replacing Mg(OH)2 with MgCl2 and enhances the degradation rate of the Mg alloy [135]. On the other side, the OH − coming initially from Mg degradation can easily react with the HPO4 2− in physiological fluids based on Equation (2), leading to the generation of PO4 3− .
Subsequently, the PO4 3− reacts with the Ca 2+ in physiological media or Mg 2+ to deposit apatite or Mg-P on the composite surface [136][137][138][139]. Phosphate ions might slow down the corrosion rate significantly and postpone the occurrence of pitting corrosion [135]. Neupane et al. [140] suggested the increased corrosion resistance of GNPs embedded within the Mg matrix. GNPs were successfully embedded into nanocomposites, which led to augmenting new bone generation and restoration because GNPs tend not to simply degrade in physiological fluids and anti-infiltrate corrosive media, thus reducing the degradation rate of the Mg-based composite [133]. A Similar examination showed that [138][139][140] the corrosion performance of Mg-based composites was enhanced by the embedding of sufficient amounts of GFNs.  Based on the previously mentioned reactions, Mg(OH) 2 is created on the Mg alloy surface. The chloride ion is considered to have an adverse effect on the corrosion resistance of Mg. Numerous investigations have verified that a high chloride amount is facilitated by replacing Mg(OH) 2 with MgCl 2 and enhances the degradation rate of the Mg alloy [135]. On the other side, the OH − coming initially from Mg degradation can easily react with the HPO 4 2− in physiological fluids based on Equation (2), leading to the generation of PO 4 3− .
Subsequently, the PO 4 3− reacts with the Ca 2+ in physiological media or Mg 2+ to deposit apatite or Mg-P on the composite surface [136][137][138][139]. Phosphate ions might slow down the corrosion rate significantly and postpone the occurrence of pitting corrosion [135]. Neupane et al. [140] suggested the increased corrosion resistance of GNPs embedded within the Mg matrix. GNPs were successfully embedded into nanocomposites, which led to augmenting new bone generation and restoration because GNPs tend not to simply degrade in physiological fluids and anti-infiltrate corrosive media, thus reducing the degradation rate of the Mg-based composite [133]. A Similar examination showed that [138][139][140] the corrosion performance of Mg-based composites was enhanced by the embedding of sufficient amounts of GFNs. Shuaia et al. [102] fabricated a Mg alloy/GO composite with a 3D honeycomb nanostructure accompanied by remarkable corrosion resistance via the SLM process. Outcomes revealed that GO dispersed along the GBs and progressively covered α-Mg grains as the GO amount increased. Because of this remarkable anti-infiltration property of GO, the honeycomb nanostructure served as a solid obstacle to inhibit the increasing corrosion rate. The oxygen-incorporating groups on GO accelerate the precipitation of apatite and additionally inhibit further attack of the corrosive solution [141,142]. Turan et al. [107] also prepared Mg-xGNPs (x = 0.1, 0.25, and 0.5 wt.%) composites via SPM approaches with GNPs. A homogeneous dispersion was attained for the entire specimens while partial agglomeration might be observed in Mg-0.5GNPs. In comparison with the bare Mg, the corrosion property was impacted adversely in composite encapsulated within graphene. In this context, Rashad et al. [143] likewise examined the influence NaCl solutions have on the corrosion performance of Mg-Gr composites. The outcomes showed that the existence of GNPs in various matrices reduces the corrosion property of the composites. They also revealed that due to the presence of dislocation amounts at the interface of composites, crevice invasions were generated, and hence, GNPs induce the corrosion of Mg/Mg alloys as a result of the galvanic cell; this particular effect increases with increasing GNP amount. The corrosion rates with various processing methods, corrosion solutions, and measurement techniques are described in Table 3.

Biodegradability of Mg-GFN-Based Composites
Commonly, GNPs tend not to simply degrade in physiological fluids; even so, their full degradation might be attained by human enzymes accelerating chemical reactions in the body [137]. GNPs offer a distinctive orientation of sp 2 carbon atoms, creating a 2D structure (honeycomb shape) with great electron density, ultimately causing an impenetrable performance against entire gas molecules, which increase the corrosion resistance of Mg alloys [47,[144][145][146][147]. The GNPs with a thin layer work as a barrier film within the metal matrix, leading to a substantial lessening in current densities and subsequent corrosion rates throughout immersion tests of composites containing GNPs [138,139]. GNPs, by possessing an atomic-scale barrier, are also favorable in reducing or suppressing H 2 gas formation in Mg-based specimens during the degradation process when exposed to the body fluids, as presented in Figure 14 [47].

Biodegradability of Mg-GFN-Based Composites
Commonly, GNPs tend not to simply degrade in physiological fluids; even so, their full degradation might be attained by human enzymes accelerating chemical reactions in the body [137]. GNPs offer a distinctive orientation of sp 2 carbon atoms, creating a 2D structure (honeycomb shape) with great electron density, ultimately causing an impenetrable performance against entire gas molecules, which increase the corrosion resistance of Mg alloys [47,[144][145][146][147]. The GNPs with a thin layer work as a barrier film within the metal matrix, leading to a substantial lessening in current densities and subsequent corrosion rates throughout immersion tests of composites containing GNPs [138,139]. GNPs, by possessing an atomic-scale barrier, are also favorable in reducing or suppressing H2 gas formation in Mg-based specimens during the degradation process when exposed to the body fluids, as presented in Figure 14 [47]. Neupane et al. [140] revealed the improved anti-corrosion behavior of GNPs embedded in Mg substrates. The impenetrability and outstanding mechanical characteristics (1100 GPa) of GNPs make them suitable as an additive phase (reinforcement agent) embedded into the Mg matrix for implant applications. As mentioned previously, the degradation of GNPs mostly takes place in enzymatic oxidation in biological fluid [148], while surface treatment of GNPs results in the attachment of specific FGs including carboxylic acid, which is favorable for degradation performance. The great specific surface areas of GNPs additionally help their degradation behavior by improving the biomolecules' attraction on the surfaces [149]. Other researchers also further confirmed that these elements likewise have an effect on the degradation process of GNPs including 2D planar sheets that offer substantially more connection surfaces with the biomolecules [150], along with the unsmooth, wrinkled surface morphology of GNPs, noticeably promoting their interlocking performance with the surrounding media, hence improving the attachment of biomolecules on their surfaces [151]. It should be mentioned that the volume fraction of GNPs in metal-based biomaterials ought to be in the amount of 1-10% due to the fact that a high concentration of GNPs results in dramatically elevated stiffness of the composite, which would possibly not be biomechanically suitable with natural bone. Neupane et al. [140] revealed the improved anti-corrosion behavior of GNPs embedded in Mg substrates. The impenetrability and outstanding mechanical characteristics (1100 GPa) of GNPs make them suitable as an additive phase (reinforcement agent) embedded into the Mg matrix for implant applications. As mentioned previously, the degradation of GNPs mostly takes place in enzymatic oxidation in biological fluid [148], while surface treatment of GNPs results in the attachment of specific FGs including carboxylic acid, which is favorable for degradation performance. The great specific surface areas of GNPs additionally help their degradation behavior by improving the biomolecules' attraction on the surfaces [149]. Other researchers also further confirmed that these elements likewise have an effect on the degradation process of GNPs including 2D planar sheets that offer substantially more connection surfaces with the biomolecules [150], along with the unsmooth, wrinkled surface morphology of GNPs, noticeably promoting their interlocking performance with the surrounding media, hence improving the attachment of biomolecules on their surfaces [151]. It should be mentioned that the volume fraction of GNPs in metal-based biomaterials ought to be in the amount of 1-10% due to the fact that a high concentration of GNPs results in dramatically elevated stiffness of the composite, which would possibly not be biomechanically suitable with natural bone.

Cellular Response of Mg-GFN-Based Composites
Regardless of the appealing features of MMNCs incorporating different nano-additive phases, safety and toxicity issues hinder their use in bone tissue engineering (BTE). The most recent advancements in nanotechnology have made it possible for experts to create composite materials presenting appealing characteristics by modulating their features on the nanoscale. Nevertheless, from the viewpoint of biomedical purposes, biological characteristics and the interaction of these nanomaterials in an SBF have remained questionable subjects as a result of unclear studies on their toxicity. For that reason, it is crucial to further examine the biological characteristics of these composites including cell response, biocorrosion, and cytotoxicity. Biodegradable materials including Mg absorb in vivo and dissolve fully after fulfilling the healing process time. The alloying elements are the key factors of biodegradable materials that might be effortlessly absorbed by the body. Nevertheless, Mg-based composites degrade quickly in physiological media prior to adequate healing of the tissues. This kind of quick degradation of Mg-based composites likewise affects their capacity to be used for load-bearing implant purposes [152]. Typically, the biocompatibility of MMNCs is determined by their connections with different biological systems including cells, proteins, and other complex biomolecules, for example DNA [152]. It is actually recognized that GFNs cause the attachment of cell-binding proteins and the following cellular attachment [153,154]. The effective binding of proteins existing in SBF and tissues on the GFNs results in the generation of biocorona protein on composite surfaces [155]. The structure of this kind of biocorona primarily relies on the intrinsic characteristics of Gr and has the ability of modifying of the extracellular matrix (ECM). Consequently, the tendencies of Gr in biological systems are usually accurately forecasted by knowing the creation procedure of biocorona on their surfaces [47,154]. Current reports likewise revealed that π-π stacking, a result of the solid van der Waals force, is actually identified as a dominant adsorption system of proteins on top of the GNPs' surfaces. This kind of solid π-π stacking mainly takes place among the solid sp 2 bonding of carbon atoms in GFNs and the benzene rings in amino acids [156,157]. Accordingly, any kind of enzymatic degradation of GNPs through the defense mechanisms of competent cells could work as a distinctive case of biocoronal interactions within the body. GNP embedded nanocomposites are effective in electrically inducing tissues owing to their outstanding conductive characteristics, and this is favorable in facilitating new bone generation and restoration. These sorts of conductive nanobiomaterials likewise enhance the adsorption of ECM proteins, hence enhancing the expression of osteogenic differentiation and the generation of pertinent growth factors. BMP is a widely recognized protein that elevates the osteogenic differentiation of Mg-based composites containing GFNs and has demonstrated outstanding attachment on the Gr surfaces [154,156,157]. In this regard, it was suggested [34] that the bacterial cytotoxicity of GFNs could possibly be caused by both membrane and oxidative stress. GFNs have a tendency to lead to cellular attachment, due to the fact that it really is more probable to interact with bacterial cells because of the greater density of FGs and small size [35]. GFNs could destroy the cells as a result of membrane stress generation, which results in destroying the cell walls [34]. This sort of biocompatibility causes this to be an appealing nano-additive phase for MMNCs. In vitro cytotoxicity examinations were performed by Saberi et al. [110] and Munir et al. [30], and no negative consequences with encapsulation of GNPs in pure Mg and Mg-based matrix, respectively, were found. Mg-based matrix with homogeneously distributed GNPs with lower defect amounts presented a greater level of cell viability ratio (CVR). Furthermore, MG-63 cells were observed by Shuai et al. [102] to be attached and to greatly proliferate on AZ61-1.0GO alloy and exhibited greater cytocompatibility as opposed to AZ61 alloy. The sluggish corrosion along with lower pH value increase cause greater cell attachment and growth on the nanocomposite surface with a lower content of GNPs [110]. Nevertheless, Saberi et al. [110] exhibited that more addition of GNPs up to 2 wt.% had an effect on cellular attachments and diminished the density and growth of the cells resulting from activating the mitochondrial pathway. Table 4 exhibits in vitro the cytotoxicity examination regarding Mg-GFN composites.

Antibacterial Performance of Mg-GFN-Based Composites
Saberi et al. [110] demonstrated that Mg-GNP composites offered great antibacterial performance towards Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria based on disk diffusion. According to the results, employing GNPs within the Mg matrix improves the inhibition zone. The charge transfers and the infiltration into the cells are the primary antibacterial systems [34,159]. As soon as the bacterial cells come into contact with the GFNs, they will likely be finally damaged as a consequence of numerous mechanisms including membrane stress, oxidative stress, and/or wrapping isolation. The bacterial development is prevented through these mechanisms that might function independently or with each other [160]. Initially, the bacterial cells were resistant to the Gr-based materials for a limited period, and subsequently, owing to a few cells having a smaller weight of surface phospholipid, the cell walls' integrity was to some extent sacrificed. Ultimately, an extreme reduction happened in the cell walls [160]. Within these conditions, the lipid bilayer is infiltrated by coming into contact with the GNPs. The membrane layer is routinely pierced by the sharp sheet edges of the GFNs, which reduce the energy required for membrane infiltration. Among the elements that could assist in the cell membrane layer destruction are the negative charges of the bacterial cells, which enhance the connections with the sheet edges, since they function as great electron acceptors.
It is suggested that the primary function of oxidative stress is the antibacterial activity of GO. Actually, the oxidation of lipids, nucleic acids, and proteins that ultimately contributes to cell membrane layer damage and cellular growth inhibition is caused by the activity of oxidative stress on bacteria [34]. The reactive oxygen species' (ROS) release is the reason for this inhibition that might result in the modification of the cellular redox circumstance. In the condition in which usually the particles are absorbed, the main systems for cellular protection are generally oxidative stress, as well as ROS release. By disturbing the equilibrium among the intracellular oxidant and antioxidant functions, the GNPs might enhance the oxidative stress [161]. The ROS, which usually can destroy cellular parts, in particular proteins and DNA, commonly includes OH, O 2− , and H 2 O 2 [162]. Following that, Gr exhibited antibacterial capacity, despite the fact that GO of similar amounts showed greater antibacterial performance than that of Gr. The main antimicrobial mechanisms were charge transfer and infiltration into the cell walls [163]. Consequently, Gr and GO with their antimicrobial capacity might fulfill the specifications regarding bone restoration components below the safety limit [161]. Another investigation [159] demonstrated that Gr seriously destroys and deactivates the microorganisms when it attaches to them. This antimicrobial action was effective and quick against E. coli and S. aureus, and the destruction took place mainly in the cell membrane layer. Based on an examination, the Gr nanosheets experienced a greater antimicrobial capacity than standard antibiotics including kanamycin. Likewise, concerning the antimicrobial mechanisms, Shuai et al. [164] revealed that the inhibitory characteristics of the Gr-based nanocomposites elevated cellular injuries owing to the occurrence of oxidative stress. In other research [163], GFNs, for instance fullerene and CNTs, were considered as the agents to generate the oxidative stress. Furthermore, consistent with some other examinations, the cell wall experiences a charge imbalance, which might destroy the cell walls. The solid connection of the negatively charged microbial cell walls with the outstanding electron acceptors Gr encapsulated nanocomposites results in the previously mentioned electrons from the bacterial membrane to the GNPs, and therefore, the microbial cell walls might be encircled by means of a conductive system. For that reason, this destroys the microbial cell by way of generating oxidative stress in the microbial cell membrane.

Future research Directions in using GFNs for Bone Tissue Engineering
The potential of Mg-based encapsulated GFNs was reviewed in the former sections, suggesting their use as new biomaterials pertaining to BTE. All of the research indicated that GFNs are appearing as new components in the associated areas of biomedicine, drug release systems, and TE, and they are developing quickly. Comprehensive investigation is continuing to set up a system for employing GFNs as the nano-additive phase in present metallic biomaterials to be able to create new and very useful implants and scaffolds for TE usage. For these kinds of nanocomposites, a lower amount of CNT and Gr (≈ 5 vol.%) was recommended, thus to restrict the portions getting into the human body system [165]. The immobilization of CNT and Gr in metallic biomaterials prevents the exposure of adjacent tissues, therefore providing biosafety for these kinds of particles [47]. It is worth noting that the application of biodegradable Mg-GFN composites fabricated through various fabrication procedures and structural modifications for load-bearing implant process for bone substitution and reproduction attracts a huge amount of attention [166][167][168][169][170][171][172][173][174][175][176][177][178][179][180]. Taking into consideration the outstanding biological response and incredible mechanical characteristics of Gr, as described in earlier sections, it is anticipated that a number of implants and scaffolds will be created in the near future. Despite the fact that the results from initial in vitro and in vivo biological tests on Gr are motivating, additional comprehensive, methodical research works are expected to comprehend their long-term biological results. With the current literature on the biomedical usage of Gr, it is still not feasible to determine them as safe components concerning BTE. Among the key factors for the inability of these nanomaterials to convert directly into clinically verified use is the absence of reliable in vivo research to evaluate their nanotoxicity. In addition to other biomedical usage, GFN-based implants and scaffolds for BTE are usually regarded as safe as there is minimal chance that these nano-additive phases in metal matrices are going to be directly connected to living microorganisms. These demands create mindful technology and scientific strategies to reduce the nanotoxicological effect of Gr even while keeping the appealing ideal characteristics regarding BTE. The current review article offers more examination to be performed to utilize GFNs as nano-additive phases for Mg-based alloys. Specifically, additional in vivo examination is required to confirm the appropriateness of these materials for implant usage.

Conclusions
This review significantly examined the possibilities, current progress, challenges, and upcoming exploration guidelines with regard to GFNs as nano-additives (reinforcements) in Mg-based matrices. Mg alloys have benefits compared to the traditional stainless steel, Co-based alloys, and Ti-based alloys because of the outstanding biodegradability and cytocompatibility along with the appropriate mechanical performance concerning implant usage . From this perspective, the mechanical characteristics of bioimplants ought to be adequate to maintain their strength throughout the healing process. Nano-additives (reinforcements) are able to enhance the mechanical integrity of Mg-based composites along with ductility at the same time. Following that, GFNs effectivity act as functional components and reinforcement phases for Mg-based composites, which offer distinctive characteristics including large surface areas and outstanding mechanical, thermal, and electrical characteristics, along with great chemical stability. The synergetic capability of GFNs to enhance ductility together with strengthening, as well as decreasing weight is extremely attractive and prevails over the drawbacks of other reinforcement phases like ceramic particles. Furthermore, GFNs, in particular GO, have considerable biological characteristics and reveal effective antibacterial performance owing to ROS release and oxidative stress. Furthermore, the fabrication process of composites such as SC, PM, SPM, SLM, and FSP, as well as other parameters including GFN amount and type have a significant effect on the mechanical, anticorrosion, and biological properties Mg-based composites encapsulated within GFNs. On top of that, apparently, the presence of GFNs, in particular GO and GNPs, within Mg-based matrices in lower amounts could provide better anticorrosion and biological properties in vitro and in vivo. In addition, there are widely recognized strengthening systems for Mg matrices; among them, refined grain structure, Orowan looping, and stress transfer are the primary strengthening mechanisms in Mg matrices strengthened by GNPs. Taken together, GFNs as nano-additive phases (reinforcement agents) offer incredible potential to be employed for load-bearing implants and BTE applications. However, the cytocompatibility of GFNs is nevertheless an arguable matter that hinders developments in employing these appealing reinforcement agents for clinical usage. Their safe clinical implementation as revolutionary reinforcement agents for application in load-bearing implants and BTE requires additional assessment.
Author Contributions: Conceptualization, supervision, formal analysis, writing-review and editing, A.S.; H.R.B.-R., writing-review and editing, S.R.; writing-original draft preparation, methodology, formal analysis, S.A.; supervision, writing-review and editing, funding acquisition, F.B. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.

Acknowledgments:
The authors would like to thank the Norwegian University of Science and Technology, Islamic Azad University, Najafabad, and Amirkabir University on Technology for providing the facilities for this research.

Conflicts of Interest:
The authors declare that they have no competing/financial conflict of interests in this paper.

MMCs
Metal