2.2.8. Alumina

Since 1975, the bio-inertness of alumina has been confirmed. Alumina has very high hardness and resistance to abrasion on the Moh scale next to diamond [385]. In addition, the crystalline nature of alumina makes it insoluble at room temperature in regular chemical reagents [386]. Alumina has been used in many fabrications of artificial implants since it was inserted into an artificial femur head in the 1970s [387]. Pure and densified alumina, α-Al2O3 (corundum), was the first ceramic material used in the biomedical field for dental restorations, cochlear implants, and load-bearing hip prostheses [388]. As porous alumina does not degrade under in vitro and in vivo environments, it may be used for biosensing [389], good electrical insulation [390], and immune isolation [391].

Properties such as abrasion resistance, power and chemical inertness favor the use of alumina in hard tissue engineering [392]. If the alumina is implanted in bone marrow, no toxic effects are generated in the surrounding tissue [393]. However, the high stiffness of alumina may lead to have a high elastic incompatibility between the biological tissue and the implant [394]. The tensile strength of alumina can be increased by reducing grain size and increasing its density [395]. In view of their good mechanical behavior, alumina implants are characterized by long-time survival predictions [396].

A significant feature in applications involving open and aligned porous structures, such as bone tissue scaffolds, catalysts, and membranes, is the anisotropic nature of porous alumina ceramics [397]. The α-alumina is the most stable oxide amongst transient and metastable types [398]. It should be noted that essential physico-chemical properties of alumina surface are significantly affected by the protein adsorption process. For example, the presence of liquid solutions nearby the implanted site can cause accelerated protein adsorption on the alumina's surface [399]. Piconi et al. [394] reported the in vitro biocompatibility of alumina with various cell lines such as fibroblasts and osteoblasts, and immunological cells with various cell environments.

The particle size of alumina may affect biocompatibility, particularly when using nanoparticles because of their high surface/volume ratio [400]. Alumina suspensions (70% wt.) and wheat flour (20–30% vol.) were used to synthesize different particle sized porous alumina ceramics [401]. Hydroxyapatite/alumina composite based foam was synthesized via a precipitation method under a variety of pH values that showed a good concentration of Ca2<sup>+</sup> and PO4 <sup>3</sup><sup>−</sup> contents [402]. The chemical modification of porous alumina surface with vitronectin and peptide (i.e., arginine-glycine-aspartic acid cysteine (RGDC)) enhanced bone cell adhesion and production of extracellular matrix [403].

Porous anodic alumina (PAA) can be fabricated on the surface of other materials through anodization process [404,405]. It can be considered a good nanocontainer to load active agents such as drugs or biomolecules [406]. Evaporation induced self-assembly derived mesoporous aluminum oxide was used for the delivery of poor-water soluble compound Telmisartan (anti-blood pressure drug) with 45% loading efficiency [407]. The drug is not loaded within the pores of the PAA completely, but the surface itself can hold some of this load, which can be quite high; this promotes another phase release [408,409].

Calcium phosphate with 20% alumina (Ca3(PO4)2–Al2O3) bio-ceramic composite revealed enhanced biocompatibility and mechanical properties [410]. Using alumina nanowires reinforcement in polyhydroxy butyrate-chitosan (PHB-CTS/3% Al2O3) scaffolds enhanced the mechanical properties of the scaffold. The addition of alumina increased by ten times the tensile strength of PHB-CTS/3% Al2O3, which became higher than its counterpart for the original PHB-CTS scaffold [411].

Al2O3 coating was used for improving the performance of stainless steel 316L and Ti-6Al-4V implants [412]. In general, coating materials are used to protect the surface of the implant material and the interface with the biological system at hand [413]. Nanorod-like HA-coated porous Al2O3 was fabricated by anodic oxidation that revealed excellent biological activity in vitro [414].
