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Biocompatibility and osteogenesis of Refractory metal implants

Refractory metals, such as cobalt, chromium, tantalum (Ta), niobium (Nb), and titanium (Ti) alloys, have been used in implants because of their excellent corrosion resistance. Cytotoxicity usually depends on the ionization tendency of the metal used. In order to evaluate the biocompatibility of refractory metals, titanium, hafnium, niobium, tantalum and rhenium were implanted in rats and organized by X-ray scanning analysis microscope (XSAM) and electron probe microscope analyzer (EPMA) Scientific observation and element map analysis.

Titanium, hafnium, niobium, tantalum, and rhenium wires were implanted into rat abdominal subcutaneous tissue and femoral bone marrow for 2 or 4 weeks. No inflammation was observed around the implants, and all the implants were wrapped in "thick" and fine connective tissue. XSAM did not detect the dissolution of these metals in soft tissues.

EPMA did not detect the dissolution of these metals in hard tissues. The Ca and P intensities in the newly formed bone mapping image 4 weeks later are higher than 2 weeks later, indicating that the newly formed bone continues to mature 2 to 4 weeks after implantation. These results indicate that titanium, hafnium, niobium, tantalum and rhenium have good biocompatibility and osteoconductivity.

Due to its excellent biocompatibility, easy availability, and sufficient strength to adapt to a small specific gravity. Ta, Nb, and Zr have also been studied and used as implant materials, and it is reported that these metals have good biocompatibility to biomaterials. Hf and Rehan are rarely used as biomaterials, and there are few reports on their biocompatibility. These materials have a very high melting temperature, high affinity with C, N, and O gas atoms, excellent corrosion resistance at room temperature by forming a protective oxide layer, and in addition to the very hard Re, it has Moderately high modulus elasticity. The biocompatibility of Hf and Re is a topic of main interest.

It is difficult to apply EPMA mapping to soft tissue analysis because the sample must be embedded in the resin to withstand the observation under vacuum. Therefore, XSAM element mapping was performed on the soft tissue samples. The elemental mapping of XSAM in soft tissue and EPMA in hard tissue did not show Ti, Hf, Nb, Ta or Rearound of the implant. The authors have reported nickel dissolution detected by XSAM. However, Ti, Hf, Nb, Ta and Re are different from Ni in that it has excellent corrosion resistance in both soft and hard tissues. The detectable limit of insoluble or dissolved below 10} 100 ppm is the basic criterion for good biocompatibility. The thickness of the newly formed bone observed by the optical microscope is about 20-30 µm, which is consistent with the thickness estimated by EPMA and SEM observations. The total amount of new bone formation observed by optical microscopy and EPMA mapping is also consistent. Two weeks later, the Ca and P intensities of newly formed bone on the EPMA map were lower than those of cortical bone. However, after 4 weeks, the Ca and P intensities increased to levels close to cortical bone. These results further support the observation that newly formed bone calcification progresses from the second week to the fourth week.

Animal implantation studies of Ti, Hf, Nb, Ta and Rein into soft and hard tissue in mice show that these metals have excellent biocompatibility and bone formation. Quantitative histological analysis of bone formation showed a slight decrease in new bone formation and a significant increase in the proportion of bone in contact with the implant between 2 and 4 weeks after implantation. XSAM cannot detect dissolution of Ti, Hf, Nb, Ta or Re in soft tissues or by EPMA in hard tissues. EPMA is effective in assessing bone calcification. The excellent resistance to corrosion of soft and hard tissues, confirmed by EPMA and XSAM mapping, is the basis for the biocompatibility of this refractory metal.


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