© 2003 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003

15.3.5 Biocompatibility of Sapphire, Ruby, and Alumina

Pure corundum (aluminum oxide or alumina) is colorless and can have a strength and hardness (Table 9.3) and a chemical inertness (Section 15.3.5.6) that is only slightly inferior to diamond. Sapphire and ruby, the best-known crystalline forms, are primarily single-crystal alpha-Al₂O₃. The crystal can be manufactured in a full spectrum of colors (Section 5.3.7). The material characteristics of sapphire are reviewed elsewhere (Section 5.3.7, Section 9.3.5.3.6, Table 9.3, etc.). Scanning force microscopy has been used to image the atomic structure of the (0001) surface of alpha-alumina crystal, and to observe the formation of hydroxide clusters after exposure to water [4796]. The atomic structure of the hydrated alpha-alumina surface has also been investigated by x-ray diffraction [1751]. The high-density single-crystal sapphire form of alumina may be produced when Al₂O₃ is compressed under isostatic pressure and fired at 1500 ^oC to 1700 ^oC [956]. Alumina nanotubes have also been synthesized [4804].

To summarize the utility of sapphire in medical nanorobotics: First, sapphire is almost as strong and hard as diamond (Table 9.3), and only slightly more dense. Second, sapphire is already fully oxidized, so in particulate form (e.g., micron-size nanorobots) it cannot burn in air like diamond, and its crystalline structure remains stable to higher temperatures than diamond. Third, sapphire has more favorable bulk thermophysical characteristics. The thermal conductivity of sapphire is 100-1000 times less than for diamond, reducing the increase in the thermal conductivity of tissues that are loaded with sapphire nanostructures, as compared to tissues containing pure-diamond nanostructures (Section 15.3.8). Sapphire also has 60% greater heat capacity per unit volume than diamond. Fourth, sapphire offers designers an alternative hydrophilic surface chemistry as compared to hydrophobic diamond. Sapphire is amphoteric, absorbing H⁺ ions in very acidic environments (acquiring a positive charge) and absorbing OH^- ions in alkaline environments (acquiring a negative charge), while remaining isoelectric (electrically neutral) at intermediate pH values near human physiologic at ~7.4 (Section 15.5.6.1). Fifth, sapphire can be manufactured in a full spectrum of colors (Section 5.3.7) by replacing 0.01%-0.1% of the aluminum atoms with atoms of iron, titanium, or chromium, while producing only modest changes in the physical and chemical properties of the material.

Apparently no studies have been done on the biocompatibility of ruby, but high-density monocrystalline sapphire [1034] and alumina (e.g., either porous or polycrystalline [970]) materials have been widely investigated and are already in extensive clinical use. (Amorphous or gamma-alumina [959] and other transitional or “activated” forms [958] are not discussed here.) For instance, sapphire is often used as a dental implant (Section 15.3.5.2), though it is so hard that it must be resected using a diamond bur [971]. Alumina [845, 972-974] and sapphire [1031-1036, 1050] are generally regarded as nontoxic bioinert ceramic materials. While the biocompatibility of sapphire appears to be in some ways slightly poorer than diamond, nevertheless in applications requiring hydrophilic, nonoxidizable, or colored surfaces, sapphire may be the better choice of nanorobotic building material [34]. Sapphire is already being used in nanofluidics [4786] and other near-term nanomedical applications, and is being considered for use in the manufacture of prosthetic heart valves [4788].

This Section briefly reviews protein adsorption on alumina and sapphire (Section 15.3.5.1), the tissue response to sapphire dental implants (Section 15.3.5.2) and other alumina and sapphire implant surfaces and prostheses (Section 15.3.5.3), the cellular response to alumina and sapphire surfaces (Section 15.3.5.4), the biocompatibility of alumina and sapphire particles (Section 15.3.5.5), and finally the chemical stability of alumina and sapphire in vivo (Section 15.3.5.6). The reader is cautioned that some of the experimental and clinical results reported here for polycrystalline or other forms of alumina ceramic may differ from results to be obtained for the atomically-precise monocrystalline sapphire likely to be employed in medical nanorobots.

Last updated on 30 April 2004