**2. Chemical and biological properties of magnesium**

As the largest dynamic biological tissue in the body, bones are composed of inorganic minerals as magnesium and metabolically active cells surrounded by a large volume of extra cellular matrix, and they form a rigid scaffold that has an irreplaceable role in maintaining life activities, including supporting the body and protecting visceral organs [1]. For bone repair, metallic materials are used to repair or replace the bone tissue damaged. The main materials used in orthopedics include stainless steel and Ti alloys because they are mechanically strong and resistant to fracture. However, there is a potential for the release of metallic ions and/or particles through corrosion and/or wear that trigger inflammatory responses that can reduce biocompatibility and lead to tissue loss [34].

Previously *in vivo* and *in vitro* studies have shown that metallic biomaterials fabricated with Mg exhibit good biocompatibility and free of systemic inflammation reaction or affection of the cellular blood composition. In addition, high mineral apposition rates and increased bone mass were found around degrading Mg implants in bone [35] also, it can present a benefic influence in metallic materials once the bone-implant interface mineralization and osseointegration are significantly greater for metallic materials like titanium and magnesium alloys (Ti-Mg), hence have shown to stimulate new bone formation when used as bone fixture.

Mg is the fourth most plentiful cation in the human body, and is an element essential in many metabolic processes, involved in the regulation of eukaryotic cell proliferation, structural functions are correlates with the enhancement of protein synthesis. Furthermore, is primarily stored in bone tissue, controlling growth of bone cells and accelerates the bone healing [36, 37], which has characteristics of bio-degradability, in the physiological environment can be eliminated and also the corrosion product of Ti-Mg alloys (Mg2+) does not cause unexpected complications because excessive Mg2+ are easily eliminated in the urine. Moreover, alloys fabricated using Mg elemental can present mechanical properties similar to those of bone, due to fabrication pores material, decreasing the elastic modulus [38, 39]. Once the bone resorption around stressshielded are in bone fixation treatments is an important consideration within clinical sectors. Because of its versatility, metallic biomaterials based on Mg can contribute to biological properties and improve the osseointegration process [40].

Mg2+ is distributed in three major compartments of the body: ~65% in the mineral phase of bone, 34% in muscle, ~1% in plasma and interstitial fluid [41] and it has a radius of 0.65 (Mg2+). Usually, at the physiological pH range, Mg2+ is hydroxylated with six H2O molecules with a large hydration energy to form a complex with a large radius of approximately 5 , also strongly interacts with phosphate ligands from nucleotides such as ATP and DNA due to its high charge/radius ratio [42]. Coordination number and spatial distribution of water molecules surrounding the Mg2+ influence its binding thermodynamics with the protein. As it can be associated with water or phosphate complex binds protein with three to five coordinating oxygen plays a major role in the protein-binding ligands.

Its charge density is approximately (.99/.65)3 3x more than that of ion calcium (Ca2+) and its affinity for electronegative ligands, almost always oxygen in biological systems, is much greater. Further, the Mg-oxygen bond length is approximately 2.05 . When Mg elemental is octahedrally coordinated by six oxygen atoms, the oxygenoxygen distance is 2.05 × 20.5 = 2.9 , an optimal van der Waals contact [43]. In biological systems, Mg ions exists in 3 different states: bound to proteins, complexed to anions, and free (Mg2+). Only free Mg has biological activity [44]. The adult human body contains approximately 24 g (1 mol) of Mg in cells × 280 mg in extracellular fluids and the skeleton represents the body's largest Mg store (approx. 60% of total Mg), divided into two subcompartments. Thus, bone functions as a large Mg reservoir, helping to stabilize its concentration in serum. About one fourth of total Mg2+ is located in skeleton muscle [45]. Bone is continuously under load, which can cause bone defects such as fatigue cracks. Such defects can be dealt with by the body's, own healing mechanism. Thus, such critical size defects (CSDs) have to be treated with an implant.
