The biomaterials area has been experiencing substantial growth in the last few years. It is estimated that the world market for these materials, which are used in the medical field and are made from metal, ceramics, synthetic or natural polymers and composites compatible with the human organism, is growing at the rate of 12 percent a year. Major studies in this field are being carried out in several Brazilian research centers, including the Chemistry Institute of Paulista State University (Unesp), in Araraquara, where professor and materials engineer Antonio Carlos Guastaldi and his team study and develop dental implants and orthopedic prostheses made out of titanium and molybdenium (Ti-Mo) metal alloys. The researcher is working on the details of a patent for development of the biomaterial, which should be deposited with INPI, the National Institute of Industrial Property, in September. If all goes well, and if companies become interested in this, he believes that the dental implants might be on the market in 2010 and that the year after that will see the first orthopedic prostheses with the new material.
An important feature of the prostheses made out of these alloys, which contain 6 to 20 percent of molybdenium in their final formulation, is biocompatibility, i.e., improved interaction with the organism. “Most of the orthopedic prostheses in the market are made out of titanium, aluminum and vanadium alloys. The problem is that vanadium is toxic,” says Guastaldi, who coordinates the Biomaterials Group at Unesp in Araraquara. “Molybdenium, besides being biocompatible, is not toxic. It lends the alloy mechanical properties that are superior to those of pure titanium implants, and that are more compatible with the organism than the conventional titanium, aluminum and vanadium alloys.” As a result of their high biological interaction and excellent resistance to corrosion, biomaterials made out of titanium are widely used in medicine, since thermodynamic stability (meaning that the material is chemically stable) is an essential condition for osseointegration. This aspect was researched by Nilson de Oliveira, a chemist, with regard to the Ti-Mo alloy, in his post-doctoral studies, in cooperation with two other research groups, one from Brazil and one from abroad. The Brazilian group was from the Physical Metallurgy and Solidification Laboratory of the Mechanical Engineering School at the State University of Campinas (Unicamp). The group abroad was from the University of Palermo in Italy, where the studies concerning these alloys’ resistance to corrosion were conducted in solutions that simulated the aggressiveness of the human body’s physiological milieu.
As for dentistry, commercially pure (CP) titanium is what is most commonly used for implants. In the orthopedic area, as titanium alone lacks the mechanical properties needed for prostheses, it is used in alloys with other chemical elements for the reconstruction of the knee, hip, face, spine and other osseous systems. One important factor in the evaluation of an orthopedic prosthesis, explains the Unesp professor, is its elasticity module, a mechanical parameter that tells us about the material’s rigidity and deformation capacity.
Ideally, the elasticity module of a prosthesis should be close to that of human bone, as this facilitates the implant load transfer to the neighboring tissues (bone, muscles, tendons). “If its module is very different, ruptures may arise between the bone and the implant in the area where the osseointegration should have occurred.” And here lies the second advantage of the titanium and molybdenium prostheses developed in Araraquara: their elasticity module (defined by the proportion between the applied tension and the resulting elastic deformation) is closer to that in human bone than traditional alloy elasticity. The bone elasticity module is expressed in gigapascals (GPa), a measure of tension. According to the researcher, this figure, for human bone, ranges from 0.1 and 20 GPa; for his team’s prosthesis, from 75 to 80 GPa; but for conventional prosthesis it ranges from 100 to 114 GPa.
Another important factor for orthopedic prosthesis implant surgery is the implant’s capacity to interact with bone tissue physicochemically, by remaining stable and bearing weight without causing pain, inflammation or becoming loose. For this to happen, the surface of the prosthesis, the region in direct contact with the body’s tissues, must be bioactive, so as to encourage the formation of bone in the fractured area. Despite titanium’s mechanical properties, resistance to corrosion and biocompatibility, its alloys are inert because they do not lead to any chemical interaction between the implant’s surface and the newly formed bone tissue. Because of this limitation, researchers from several countries are studying surface treatments that might improve the adhesion and fixation of newly formed living tissue on the bone-implant interface. Several techniques have been researched in order to improve osseointegration, including lasers to modify the structure of the implant’s surface. This was the path taken by Guastaldi’s team. “Using a high-powered laser can lead to the formation of nanostructured surfaces, as well as of oxides on the material’s surface. Some of the new compounds formed are recognized and accepted by the organism, helping adhesion and cell proliferation and differentiation, besides furthering osseointegration on a nanometric scale.” Thus, the amount of bone formed in that place is bigger, for a longer amount of time.
The team also conducted studies that involved covering the implant’s surface with hydroxyapatite, a calcium and phosphorus compound, thereby making it bioactive. This material is considered in connection with bone regeneration and substitution because it is chemically and structurally similar to the mineral part of the bones and teeth. Additionally, its presence on the implant’s surface creates the physicochemical conditions needed for bone cells to proliferate, also making it possible to plan the chemical composition of the surfacing, thereby improving the implant’s physical, chemical and biological actitivies, as is the case with the implants developed for diabetics. The surfacing with hydroxyapatite was only performed on the Ti-cp pieces to be used in dental implants, but the group’s intention is to repeat the same study with the Ti-Mo alloys for orthopedic use.
The research of the Araraquara Biomaterials Group is at an advanced stage, but still has a long way to go before the materials created at university’s laboratories can be turned into products that are ready to be marketed and available to dentists and physicians. The early trials showed that the alloys are resistant to corrosion and appropriate for use as biomaterial. The subsequent stage of the research was to conduct in vitro tests. Metal disks made with Ti-Mo alloys, 1 cm in diameter and 2 mm thick, were placed in an undifferentiated (stem) cell culture for the researchers to assess whether bone cells would form, this being an indispensable stage of the osseointegration process. The success of these trials led the researchers to advance to in vivo trials, conducted in cooperation with other research groups from the Araçatuba and Araraquara schools of dentistry, both of which belong to Unesp, as well as with foreign groups, in Portugal (University of Ilha da Madeira) and in Italy (University of Chiete-Pescara).
Screw-shaped implants, 10 mm long and 3.5 mm in diameter, were inserted in rabbits’ tibia and removed 4, 8 or 12 weeks later, for the osseointegration pattern to be analyzed. Some of the implants had had laser surface treatment and others had not. “These trials showed that there was greater bone formation and growth in the laser-treated implants surfaced with hydroxyapatite than in commercial implants,” highlights Guastaldi. “They also proved that our Ti-Mo prostheses are efficient and biocompatible, and that the chemical bonds established between the implant and the bone are stronger than the mere physical adhesion found in most commercial implants.”
Human clinical trials are not yet scheduled and will only occur once a company shows interest in producing the prostheses. According to the researcher, there already is a firm in the dental field (whose name he would rather not reveal) interested in learning more about the titanium and molybdenium implant with laser surface treatment and surfacing with hydroxyapatite. The bone prostheses will take longer to reach the marketing stage, because the studies on the deposition of hydroxyapatite must be completed and trials on humans conducted.
1. Development of Ti-Mo metal alloys applied as implant biomaterial (nº 05/04050-6); Type Regular Research Awards; Coordinator Antônio Carlos Guastaldi – UNESP; Investment R$ 82,950.00 (FAPESP)
2. Modification of the surface of implants using laser beams and surfacing with apatites through the biomimetic method (nº 05/04109-0); Type Regular Research Awards; Coordinator Antônio Carlos Guastaldi – UNESP; Investment R$ 287,812.50 (FAPESP)
OLIVEIRA, N. T. C.; GUASTALDI, A.C. Electrochemical stability and corrosion resistance of Ti-Mo alloys for biomedical applications. Acta Biomaterialia. v. 5 (1), p. 399- 405, 2009.
OLIVEIRA, N. T. C.; ALEIXO, G.; CARAM, R.; GUASTALDI, A. C. Development of Ti-Mo alloys for biomedical applications: microstructure and electrochemical characterization. Materials Science and Engineering: A. v. 452/3, p. 727-731, 2007.