Titanium biocompatibility

Titanium is considered the most biocompatible metal due to its resistance to corrosion from bodily fluids, bio-inertness, capacity for osseointegration, and high fatigue limit. Titanium's ability to withstand the harsh bodily environment is a result of the protective oxide film that forms naturally in the presence of oxygen. The oxide film is strongly adhered, insoluble, and chemically impermeable, preventing unfavorable reactions between the metal and the surrounding environment.^[3]

It has been suggested that titanium's capacity for osseointegration stems from the high dielectric constant of its surface oxide, which does not denature proteins (like tantalum, and cobalt alloys).^[4] Its ability to physically bond with bone gives titanium an advantage over other materials that require the use of an adhesive to remain attached. Titanium implants last longer and much higher forces are required to break the bonds that join them to the body compared to their alternatives.^[5]

The surface properties of a biomaterial play an important role in determining cellular response (cell adhesion and proliferation) to the material. Titanium's microstructure and high surface energy enable it to induce angiogenesis, which assists in the process of osseointegration.^[6]

Titanium can have many different standard electrode potentials depending on its oxidation state. Solid titanium has a standard electrode potential of −1.63 V. Materials with a greater standard electrode potential are more easily reduced, making them better oxidizing agents.^[7] As can be seen in the table below, solid titanium prefers to undergo oxidation, making it a better reducing agent.

Titanium naturally passivates, forming an oxide film that becomes heterogeneous and polarized as a function of exposure time to bodily environments.^[10] This leads to the increased adsorption of hydroxyl groups, lipoproteins, and glycolipids over time.^[10] The adsorption of these compounds changes how the material interacts with the body and can improve biocompatibility. In titanium alloys such as Ti-Zr and Ti-Nb, zirconium and niobium ions that are liberated due to corrosion are not released into the patient's body, but rather added to the passivation layer.^[11] The alloying elements in the passive layer add a degree of biocompatibility and corrosion resistance depending on the original alloy composition of the bulk metal prior to corrosion.

Protein surface concentration, (${\displaystyle \Gamma }$), is defined by the equation

${\displaystyle \Gamma ={Q_{\text{ADS}}M \over nF}}$^[12]

where Q_ADS is the surface charge density in C⋅cm⁻², M is the molar mass of the protein in g⋅mol⁻¹, n is the number of electrons transferred (in this case, one electron for each protonated amino group in the protein), and F is the Faraday constant in C⋅mol⁻¹.

The equation for collision frequency is as follows:

${\displaystyle v_{\text{c}}={2\pi DcdN_{\text{A}}}}$^[12]

where D = 8.83 × 10⁻⁷ cm²⋅s⁻¹ is the diffusion coefficient of the BSA molecule at 310 K, d = 7.2 nm is the "diameter" of the protein which is equivalent to twice the Stokes radius, N_A = 6.023 × 10²³ mol⁻¹ is the Avogadro constant, and c* = 0.23 g⋅L⁻¹ (3.3 μM) is the critical bulk supersaturation concentration.

Wetting occurs as a function of two parameters: surface roughness and surface fraction.^[13] By increasing wetting, implants can decrease the time required for osseointegration by allowing cells to more readily bind to the surface of an implant.^[5] Wetting of titanium can be modified by optimizing process parameters such as temperature, time, and pressure (shown in table below). Titanium with stable oxide layers predominantly consisting of TiO₂ result in improved wetting of the implant in contact with physiological fluid.^[14]