Nanomedicine, Volume IIA: Biocompatibility
© 2003 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003
Thrombosis on blood-exposed graphite-coated prostheses was first studied in the 1960s , and in the 1970s it was found that graphite-based endoprostheses were generally nontoxic and produced no immunological reactions . Glow discharge treatment to a graphite surface increases hydrophilicity, producing stronger adsorption of hydrophilic protein molecules and a more homogeneous distribution . (See also Section 126.96.36.199.) Graphite began to be studied as an implant surface material in the 1990s, owing to its use in joints , bone [942, 943], heart valves , and as an electrode in biosensors [945-949, 4841-4845].
In the best study of bulk graphite biocompatibility to date, Eriksson and Nygren  investigated the initial reactions of graphite and gold with blood by short-time exposure to capillary blood and detection of surface-adsorbed plasma proteins and cells with an immunofluorescence technique. Antibodies specific to fibrinogen, complement factors C1q and C3c, prothrombin/thrombin, von Willebrand factor, and platelet- and leukocyte-membrane antigens were used. Fibrinogen was the most abundant plasma protein immobilized on either surface, and dense populations of platelets adhered to the protein layer. Complement factors and prothrombin/thrombin were found on the graphite surface, localized in fibrin clots or related to platelets. Platelets were activated (e.g., expression of selectin CD62) on both surfaces but more extensively on the gold surface. Activation of polymorphonuclear granulocytes (PMNGs), measured as the expression of integrin CD11b, was seen on both surfaces but with different kinetics. On the graphite surface the CD11b expression was only transient, whereas on gold it increased with time. The data suggest that graphite is more thrombogenic than gold, but is also less inflammatory .
What about graphitic particles? Graphitosis from inhaled natural (impure) graphite dusts was mentioned in Section 15.1.2. But when rats were exposed to a single dose of synthetic (pure) graphite dust, particles were steadily cleared from the lungs . Alveolar macrophages contained ingested particles throughout the entire 3-month experimental period . At 100 mg/m3 exposure, no pulmonary inflammation or macrophage activation was seen. A 500 mg/m3 exposure produced transient inflammation and macrophage activation for only about 24-48 hours . Graphite is generally regarded as biologically inert. In one study , for example, human airway epithelial cells cultured with charcoal and graphite particles did not stimulate production of IL-8 or GM-CSF (granulocyte-macrophage colony-stimulating factor).
Graphite particles have persistence in the dermis and as a result are often used as a pigment in tattoos . In grade school this author accidentally stabbed his palm with a sharp pencil. Four decades later the resulting embedded graphite spot is still visible subepidermally with no evidence of inflammation or heavy fibrous encapsulation, though granulomas from this source are not unknown . Wear particles from graphite-based endoprostheses generally do not produce any severe inflammatory reactions . In one experiment , the hemolysis eventually initiated in vitro by various ceramic powders tested, including diamond, graphite and alumina, was almost zero.
Engineers contemplating the design of nanorobotic structures with graphitic exteriors should be aware that the growth of bacteria is often enhanced by the addition of carbon materials such as graphite or activated charcoal to the growth medium. Matsuhashi et al  have isolated bacterial strains that strictly require such carbon materials under the ordinarily lethal stress caused by high concentrations of salt. The organisms are Gram-positive, spore-forming, sugar-nonfermenting aerobic bacilli provisionally designated Bacillus carbophilus Kasumi. The growth- and germination-promoting effects of graphite and activated charcoal were demonstrated either quantitatively on agar plates containing fine crystals of the carbon materials mixed with a nonpermissive growth medium or qualitatively on agar plates on nonpermissive growth media half-covered with fine carbon particles. Further experiments  demonstrated a novel feature of the phenomenon: the ability to induce colony formation on the nonpermissive plate was transmissible through the air, as well as through plastic or glass barriers, via a mechanism which the researchers believe may involve transmission of physical signals regulating cell growth.
Chemically, graphite is insoluble in common solvents but is attacked by strong oxidizing agents such as mixtures of sulfuric acid with nitric acid, chromic acid, or chlorates, giving graphitic acids and finally mellitic acid, C6(COOH)6, whereas diamond is unaffected by such treatment . Thin carbon films, when used as coatings on prosthetic devices, often serve as a barrier to gases and physiological fluids. The average gas permeability constant of 20-50 nm thick carbon films to room-temperature CO2 was measured as 1.91 x 10-12 cm3-cm/cm2-sec-mmHg, a value comparable to or smaller than that of nuclear graphites which are considered to be impermeable to gases . The heat of immersion evolved when graphite is brought into contact with solvent water has been measured for Graphon surface as 32.4 erg/cm2 , vs. 66.7 erg/cm2 for LTI carbon , 203 erg/cm2 for glass , and 210 erg/cm2 for amorphous silica .
Last updated on 30 April 2004