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 Biocompatibility of Diamond-Coated Prostheses

Diamond has been touted as “the biomaterial of the 21st century” [596], and many uses for diamond surfaces in biomedical applications [604, 4724] have been proposed including coatings for artificial heart valves [548, 550, 594], prosthetic devices [549, 550, 657, 659], joint replacements [593, 605, 606, 4729, 5688], catheters and stents [594], orthopedic pins [547], the roots of false teeth [547], dental instrument tips [594], surgical scalpels and microtome blades [548, 549], and even the complete fabrication of artificial heart valves [548]. Diamond electrodes also are widely employed in biosensors [4831-4836].

So far, the largest anticipated use of biomedical diamond is in orthopedics and articulated prostheses. Early in vivo experiments involving diamond-like carbon (DLC) coated orthopedic pins implanted in sheep demonstrated low diamond bioactivity [546, 547], and implants of DLC-coated zirconium placed in the tibiae of Wistar rats for 30 days showed good osseointegration at the tissue-implant interface [607]. Chemical vapor deposition (CVD) diamond coatings for artificial joints are said to have “low immunoreactivity” [535], and in vitro testing of possible intra-articular diamond wear particles finds these particles “comparatively harmless” [605, 608]. DLC coatings deposited onto austenitic stainless steel hip implants and tested for cytotoxicity, cell adhesion (human fibroblasts) and mutagenicity in vitro showed good biocompatibility, as did in vivo tests of DLC-coated stainless steel cylinders 4 mm wide inserted into cortical bone and muscular tissue of sheep [659]. Allen et al [4722] implanted DLC-coated cobalt-chromium cylinders in intramuscular locations in rats and transcortical sites in sheep, and all implants were well tolerated as determined upon specimen retrieval 90 days after surgery. This indicates that DLC coatings are biocompatible both in vitro and in vivo, in musculoskeletal systems. Other DLC-type coatings for bone implants have also shown good biocompatibility [4727] and toughness – in some cases, abrasive wear on amorphous diamond “is negligible compared with conventional hip joint materials” [4728].

Amorphous diamond coatings (80% sp3 bonding fraction, 0.2-10 microns thick; sp2/sp3 film structure experimentally adjustable [4743]) deposited on stainless steel alloys via filtered pulsed-plasma arc discharge were found to be biocompatible causing no local tissue reactions. These coatings have been studied with the objective of attempting a total hip replacement [609]. Some DLC-coated metal prostheses have been implanted in humans [594] and the results appear promising [608, 657]. For massive prostheses which are used to replace large segments of bone which are resected for bone tumors or for revision after failed standard prostheses, DLC coatings were tested and found to be the best of all surface finishes investigated [610]. Conformal coatings of DLC for geometrically complex mechanical structures to uniform thickness and quality [538] is challenging with current technology [5712-5714] but will become easy to do using the future techniques of positionally-controlled molecular manufacturing (Chapter 2).

Cardiac applications are another major area of active investigation of biomedical diamond coatings [4731]. In the late 1990s, all mechanical heart valves were still very thrombogenic, requiring mandatory high-dose warfarin treatment. But it was believed that DLC coatings [597] and plasma or glow discharge treatment (GDT) of mechanical valves [611] could reduce the extent of valve-related thrombogenesis by surface modification including (1) cleaning of organic and inorganic debris, (2) generating reactive and functional groups on the surface layers without affecting their bulk properties, and (3) making the surfaces more adherent to endothelial cells and albumin and less adherent to platelets, thus improving thromboresistivity [611]. A compact (~6 x 6 cm, 280 gm) centrifugal blood pump that was developed as an implantable left ventricular assist system (Chapter 22) has the entire blood-contacting surface coated with diamond-like carbon (DLC) to improve blood biocompatibility [612]. DLC or crystalline diamond coatings have often been recommended as the best possible coating material for blood-contacting LVAD surfaces [596, 613, 1680].

Diamond-coated catheters have been proposed [594], and their advantages would include lubricity, biocompatibility, low adhesion surface, impermeability and flexibility. DLC coatings generally adhere well to other catheter materials [594]. However, far more progress has been made in applying diamond coatings to stents (Section Stents are used to prevent narrowing or closure of luminal systems and to ensure adequate flow through them [614]. They have been implanted in the coronary and peripheral arteries, in central veins, in the bronchi and the esophagus, and in the urethra and biliary duct [594]. Stents have traditionally been metallic because of the necessary mechanical requirements such as high expansibility with thin walls and high circumferential strength, but metal surfaces are thrombogenic [620-623]. Corrosion resistance is dependent upon formation of a passive oxide film. If breached, metal ions are released, causing a foreign body inflammatory reaction [615-620] with a risk of tumor development [624]. The ideal stent should meet stringent requirements regarding thrombogenicity, biocompatibility and structure [625].

Phytis L.D.A., a German stent-making company,* has developed a stainless-steel stent 60-80 microns thick that is entirely coated with a diamond-like layer which the company claims greatly reduces thrombogenicity and enhances biocompatibility [626]. The Phytis stent (Figure 15.11) is pressed into the intima of the blood vessel at high pressure (15-16 atm) during implantation, but is designed to reduce the cutting trauma [627] that normally takes place. Tests sponsored by the company showed that albumin adsorption was 20-fold less on the DLC coated stents than on SiO2 and TiO2 controls [583]. There was also a significant reduction of thrombogenic potential by the DLC stents compared to uncoated stents, which is further reduced for heparin-coated DLC stents [628, 4723]. Other diamondlike stent coatings are also biocompatible [4725, 5711]. DLC exhibits high flexibility compared with diamond as manifested in application in stent coatings where the cylindrical wired material expands to twice its diameter. This mechanical flexibility may be useful in the design of nanorobots.

* In December 2002, Phytis Corp. [5839] reported the “closing of our company branch” and characterized their business “as temporarily terminated.”

Finally, an intraocular lens coated with a diamond-like carbon (DLC) film has been developed and its physical properties preliminarily investigated [555].

It is important to reiterate that some nanomedical applications will demand a nonadhesive interface, while other applications will require complete tissue integration with the implant using biocompatible surfaces of engineered bioactivity, probably including atomically-precise nanostructured material surfaces that can promote and stabilize cell attachment [629]. Biocompatibility is highly application-specific – both adhesive and nonadhesive interfaces can be “biocompatible.”


Last updated on 30 April 2004