Tantalum has been widely used in clinical research for more than 50 years:
• As a radiographic marker for diagnosis due to its high density
• As a permanent bone implant material to prevent bone displacement
• As a vascular clamp, because a special advantage of tantalum is that it is non-ferromagnetic and therefore highly suitable for MRI scanning
• For skull defect repair – the Chinese medical material standard contains information on the use of tantalum in this area
• As a flexible stent to prevent arterial rupture
• As a stent to treat biliary and arteriovenous (hemodialyzer) fistula stenosis
• For fracture repair
• For dentistry
• Many other applications
(i) Physical properties
The mechanical properties of tantalum and its alloys can reach 1000dg.C. Tantalum has a strong corrosion resistance and can only be corroded by hydrofluoric acid formed by hydrolysis of strong acids and alkalis.
Tantalum symbol Ta
Atomic number 73
Average atomic weight 180.95
Periodic table, groups VB with vanadium and niobium
Density 16.6 g.cm3
Melting point 3000 dg.C Although tantalum is a reactive metal (based on its position in the periodic table), it is an excellent metallic material for practical applications.
(ii) Material response
There are very limited published data on in vitro studies predicting in vivo degradation. Tantalum is covered with a very low solubility tantalum oxide film over a wide range of pH and pO2 combinations that reflect biological conditions. The tantalum/tantalum oxidation equilibrium reaction cannot be directly characterized due to the protective effect of the oxide. In vivo corrosion release is very mild and there are no reports of local, systemic or distal concentrations associated with corrosion release. The most common observation in animal and clinical reports is the lack of visible corrosion or corrosion products. In a specific biocompatibility study, Watari et al. investigated tantalum implanted in the abdominal subcutaneous tissue and femoral bone marrow of rats for 2 or 4 weeks.
No dissolution of the metal was detected in soft tissues by X-ray scanning analytical microscopy (XSAM) and in bone by electron probe microanalyser (EPMA) localization procedures. The study concluded that tantalum has acceptable biocompatibility as a biomaterial. If migration between the implant and the tissue occurs, then slight discoloration may occur in some cases. This is similar to the case with titanium and titanium alloys and may be caused by the removal of oxidized particles. Ingestion of tantalum and tantalum oxides results in very low absorption of tantalum into the respiratory or gastrointestinal systems, reflecting the low solubility of tantalum as a material. Tantalum is rapidly cleared from the lungs, respiratory tract and esophagus in animals and humans in the absence of respiratory disease.
(iii) Host response
Tantalum particles (10-50 μm) and pure titanium did not cause growth inhibition in human skin fibroblast cultures. Other groups have lacked associations with tantalum for biological effects with some other metals and alloys, including stainless steel and pure titanium. Normative data on the toxicological effects of tantalum are difficult to find. References indicate that no human disease is known to be caused by tantalum, that systemic poisoning in industrial settings has an unknown cause, and that tantalum and tantalum compounds are not listed as presumed or possible carcinogens. One reference cites an oral LD50 (median lethal dose) of tantalum pentoxide in rats of more than 8 g/kg body weight. In animal models injected with labeled tantalum, only 15% of the tantalum was retained in the body, with the remainder rapidly cleared from the body. Of the tantalum retained in the body, 40% remained in the bone.
Early studies did report abscesses following tantalum deposition in the human brain, however, infection was considered the underlying cause rather than a tissue reaction to the implanted material. In addition, some early clinical studies have been questioned due to issues with the source, purity, and preoperative cleaning and sterilization procedures of the implanted tantalum. When implanted in humans as foil, wire, rod, or ball, there are several reports that tantalum can act as an osseointegrated material. That is, the bone attaches directly to the implant without affecting the soft tissue layer or capsule. It has been suggested that this is because tantalum, like titanium, has a non-conductive surface oxide that does not denature proteins and thus allows for bone integration. Support for this is provided by Zitter et al., who described an in vitro system for measuring the current density of metals in implants. These measurements were consistent with the results of in vivo biocompatibility studies. In their study, the lowest current density values were obtained for pure metals such as titanium, niobium, and tantalum, which is associated with the high biocompatibility of these materials. The low current density of these materials is due to the stable oxide layer of these base metals. The stable oxide layer prevents the exchange of electrons and thus avoids any redox reactions. Therefore, these materials are bioinert. Bobyn et al. (1) used 75%-80% porous cylindrical tantalum implants in a 52-week canine study implanted in the femur. The study clearly demonstrated bone ingrowth into the implant due to the high early fixation strength of the porous tantalum implants. No signs of adverse reactions were reported during the use of these materials. A study by Kato et al. on alkali metal and heat-treated tantalum described the ability of tantalum to bind to bone in rabbits. No histological effects suggesting adverse effects of implantation were found. Bobyn et al. (2) investigated the effects of implanted tantalum biomaterials on bone tissue in dogs undergoing bilateral hip replacement. Porous tantalum showed good bone growth and histopathological examination confirmed the good biocompatibility of the implants. In vitro studies by Sharma et al. showed that the oxide layer on the tantalum surface enhanced protein adsorption at the interface. A variety of protein mixtures were used in the study, including albumin, globulin, and fibrinogen. One reason for the good biocompatibility of tantalum implants is that proteins adsorb to the tantalum surface rather than denaturation of the proteins.
Tantalum is considered bioinert in several studies and has therefore been selected as a negative control in some experimental situations. For example, Miller et al. used tantalum as a negative control in a study in which urine and plasma samples were collected from rats implanted with tantalum and tested for mutagenic activity using the Ames test. All results were negative. Chronic implantable stimulating electrodes are being developed for neuroremediation in order to alleviate neurological deficits. A comparative study by Johnson et al. investigated the use of tantalum-tantalum oxide electrodes for brain implantation in cats. At the end of the study, the electrodes were removed and found to be loosely wrapped by a fibrous sheath of dura-arch connective tissue. There was no tissue attachment to the electrode surface. Histologically, a slightly thickened pia mater was seen with a mild subpial glial reaction, but no neuronal or inflammatory response in the cortical area. The study concluded that tantalum-tantalum oxide electrodes cause less tissue damage than rhodium, platinum, or carbon electrodes, and that tantalum-tantalum oxide electrodes do not produce neurotoxic effects.
(iv) Clinical relief
Tantalum has been used clinically for more than 50 years
• As a radiographic marker for diagnosis due to its high density
• As a permanent bone implant material to prevent bone displacement
• As a vascular clamp, because a special advantage of tantalum is that it is non-ferromagnetic and therefore highly suitable for MRI scanning
• For skull defect repair – the Chinese medical material standard contains information on the use of tantalum in this regard
• As a flexible stent to prevent arterial rupture
• As a stent to treat biliary and arteriovenous (hemodialysis) fistula stenosis
• For fracture repair
• For dentistry
• Many other applications
Aronson et al. studied the use of tantalum needles and spherical tantalum markers implanted in rabbit and child bone and soft tissue for radiographic imaging. No macroscopic reaction was observed around the markers, and the markers implanted in the bone were firmly fixed and in close contact with the adjacent bone plates. Microscopic examination of rabbits showed no bone reaction or mild fibrosis, and mild fibrosis was observed after 6 weeks, but no or only mild inflammatory reaction. At 48 weeks after implantation, children showed no inflammatory reaction and only mild fibrosis. The article concludes with a review of the bioinertness of tantalum.
Conclusion
The available information indicates that tantalum is highly resistant to chemical attack and causes few adverse biological reactions in either the reduced or oxidized state. Many studies have demonstrated the good biocompatibility of tantalum in a variety of application settings, including bone surgery. In standardized procedures, metals coated with tantalum and the tantalum itself do not release any substances into the extraction medium, and surface analysis has also shown low impurity distribution.
If tantalum used in medical devices meets appropriate purity standards, then further biocompatibility studies in animals are not necessary.