JOM • March 200846 www.tms.org/jom.html

OverviewBiological Materials Science

Titanium alloys are considered to be the most attractive metallic materialsfor biomedical applications. Ti-6Al-4Vhas long been favored for biomedicalapplications. However, for permanentimplant applications the alloy has apossible toxic effect resulting from re-leased vanadium and aluminum. Forthis reason, vanadium- and aluminum-free alloys have been introduced forimplant applications.

INTRODUCTION

Materials used for biomedical appli-cations cover a wide spectrum and mustexhibit specific properties. The mostimportant property of materials usedfor fabricating implants is biocompati-bility, followed by corrosion resistance.The main metallic biomaterials arestainless steels, cobalt alloy, and titani-um and titanium alloys. Stainless steel was the first metallicbiomaterial used successfully as an im-plant. In 1932, the cobalt-based alloynamed Vitallium was developed formedical applications. Titanium is thenewest metallic biomaterial. In bothmedical and dental fields, titanium andits alloys have demonstrated success asbiomedical devices.

MEDICAL APPLICATIONSAND BIOCOMPATIBILITY

Titanium alloys are now the most at-tractive metallic materials for biomedi-cal applications. In medicine, they areused for implant devices replacingfailed hard tissue. Examples include ar-tificial hip joints, artificial knee joints,bone plates, screws for fracture fixa-tion, cardiac valve prostheses, pace-makers, and artificial hearts. Ti-6Al-4Vhas long been a main medical titaniumalloy. However, for permanent implantapplications the alloy has a possible

Biomedical Applications of Titaniumand its AlloysC.N. Elias, J.H.C. Lima, R. Valiev, and M.A. Meyers

toxic effect resulting from released va-nadium and aluminum. For this reason,vanadium- and aluminum-free alloyshave been introduced for implant appli-cations, based on the Ti-6Al-4V im-plants. These new alloys include Ti-6Al-7Nb (ASTM F1295), Ti-13Nb-13Zr (ASTM F1713), and Ti-12Mo-6Zr (ASTM F1813). A great number of in-vivo and in-vi-tro titanium experiments have beendone at universities and industriesthroughout the world for the last 50years. These experiments found thatthe excellent biocompatibility of tita-

nium is associated with its oxides. C.B.Johansson1 demonstrated in in-vivoanimal model studies that the titaniumoxide may differ from metallic bioma-terials such as Ti-6Al-4V, CoCr alloys,and stainless steel 316 LVM. The inter-face between the titanium implant andthe bone is a thin proteoglycans layer. Commercially pure titanium (Cp Ti)is considered to be the best biocompat-ible metallic material because its sur-face properties result in the spontane-ous build-up of a stable and inert oxidelayer. The main physical properties oftitanium responsible for the biocom-patibility are: low level of electronicconductivity, high corrosion resistance,thermodynamic state at physiologicalpH values, low ion-formation tendencyin aqueous environments, and an iso-electric point of the oxide of 5–6. In ad-dition, the passive-film-covered surfaceis only slightly negatively charged atphysiological pH, and titanium has adielectric constant comparable to thatof water with the consequence that theCoulomb interaction of charged spe-cies is similar to that in water.

DENTISTRY APPLICATIONS

Titanium and its alloys are also usedfor dentistry devices such as implants,crowns, bridges, overdentures, anddental implant prosthesis components(screw and abutment). Commerciallypure titanium is used preferentially forendosseous dental implant applica-tions. There are currently four cp Tigrades and one titanium alloy speciallymade for dental implant applications.These metals are specified according toASTM as grades 1 to 5. Grades 1 to 4are unalloyed, while grade 5, with 6%aluminum and 4% vanadium, is thestrongest. According to ASTM F67and F136, the titanium bar mechanical

How would you……describe the overall significance of this paper?

This article enumerates somematerials used for biomedicalapplications, emphasizing the useof commercially pure titanium fordental implants, and explains theimportance of titanium chemicalcomposition on osseointegration.

…describe this work to a materials science and engineering professional with no experience in your technical specialty?

Ultrafine grain titanium shouldhave adequate biocompatibilityand higher mechanical propertiesthan commercially pure titanium.Dental implants were insertedin a rabbit and no statisticaldifference was observed betweenthe osseointegration of cp Tiand ultrafine grain titanium.

…describe this work to a layperson?

In medicine titanium alloys are usedfor implant devices replacing failedhard tissue. This article comparesbiocompatibility properties ofdifferent biomaterials and showsthat ultrafine grain titanium hasadequate biocompatibility fordental implant use.

2008 March • JOM 47www.tms.org/jom.html

Table I. Selected Mechanical Requirements Properties of Titanium Bar for Implant*

ASTM Grade

Property 1 2 3 4 5

Yield Strength (MPa) 170 275 380 483 795Ultimate Tensile Strength (MPa) 240 345 450 550 860Elongation (%) 24 20 18 15 10Elastic Modulus (GPa) 103–107 103–107 103–107 103–107 114–120

*Adapted from ASTM F67 (Grade 1 to 4) and F136 (Grade 5).

properties of grades 1 to 5 are summa-rized in Table I. Titanium grade 1 has the highest pu-rity, lowest strength, and best room-temperature ductility of the four ASTMtitanium unalloyed grades. Grade 2 ti-tanium is the main cp Ti used for indus-trial dental implant applications. Theguaranteed minimum yield strength of275 MPa for grade 2 is comparable tothose of annealed austenitic stainlesssteels. Titanium grade 3 has 0.30 maximumiron content, which is lower than grade4 (0.50 maximum). Grade 4 has thehighest strength of the unalloyedASTM grades. Grade 5, an ASTM tita-nium alloy (Ti-6Al-4V), is the mostwidely used titanium alloy in medicalimplants but not common in dental im-plants. The alloy is most commonlyused in the annealed state. Titanium and Ti-6Al-4V present lowshear strength and low wear resistancewhen used in an orthopedic prosthesis.Also important is the mismatch ofYoung’s modulus between the titaniumimplant (103–120 GPa) and bone (10–30 GPa), which is unfavorable for bonehealing and remodeling. Some researchhas been done to resolve these prob-lems and many new titanium alloyshave been developed for biomedicalapplications. However, there is a con-tradiction between the elastic modulusand other mechanical properties. Whenthe elastic modulus is reduced, thestrength of the titanium alloy is also de-creased. Conversely, when the strengthis enhanced, the elastic modulus is alsoincreased. Several studies have compared cp Tito Ti-6Al-4V implants inserted in rab-bit bones. It has been shown that whentwisted, the cp Ti implant has higherremoval torque values than Ti-6Al-4Vscrews and significantly higher bonecontacts.2

DENTAL IMPLANTS

There are three types of dental im-plant: osseointegrated, mini-implantfor orthodontic anchorage, and zygo-matic. Each group needs different me-chanical properties and must be madeof cp Ti or a titanium alloy.

Osseointegrated Implant

The osseointegration of dental im-plants was initially defined by P.-I.Branemark et al.3 as a direct bone-to-implant contact and later on defined ona more functional basis as a directbone-to-implant contact under load. In the past, osseointegrated endosse-ous dental implants have been made ina variety of shapes, including hollowbaskets, blades, tripods, needles, disks,truncated cones, cylinders, and screws.Currently the most commonly useddental implant has a screw shape and ismade of cp Ti or Ti-6Al-4V, as shownin Figure 1. The dental implants areavailable with diameters from 3.3 mmto 6.0 mm and lengths from 6 mm to 16mm. To understand the importance of thematerial properties and function of an

osseointegrated dental implant, onemust first be knowledgeable of the im-plant parts, as shown in Figure 2. Al-though each available implant systemhas a different shape, the parts are thesame. The implant is the main compo-nent that actually has bone contact. Toimprove the biological response to tita-nium, different implant surface modifi-cations have been introduced. Tissuereactions following implantation areinfluenced by physiochemical proper-ties of the implant surface. Figure 3shows an implant with good wettabilitysurface during the surgery. The secondcomponent is the abutment, whichgives the connection between the im-plant and the prosthesis and makescontact with soft tissue. Usually theabutment is connected to the implantwith a screw, or it can be cemented.The third part of the implant structureis the prosthesis, which can be attachedto the abutment with a screw or cement.The implant is made with cp Ti or a ti-tanium alloy, the abutment with a tita-nium alloy, and the abutment screwwith a titanium or gold alloy. Some designs of titanium dental im-plants and their prosthesis componentshave a small diameter and thicknesswall, especially with internal abutmentfixation (see the last five implants inFigure 1). In these cases the implantmust be made of Ti-6Al-4V to preventfracture. However, when titanium al-loys are implanted, higher levels of thecomponent elements can be detected intissues locally and systemically.4

L. Morais et al.4 analyzed the vana-dium ion release during the implant

Figure 1. Examples of commercial dental implant designs. (Courtesy of Conexão Sistema e Prótese, Brazil.)

JOM • March 200848 www.tms.org/jom.html

Table II. Dental Implant Removal Torque (N·cm) after 8 Weeks

Inserted in Rabbit Tibia

Average Deviation

Ti ASTM Grade 2 17.0 4.2Ultrafine Grain Ti Grade 2 18.9 1.9

healing process. Titanium alloy im-plants were inserted in the tibiae of rab-bits. After 1, 4, and 12 weeks, theywere submitted to removal torque test-ing. The kidney, liver, and lung wereextracted and analyzed by atomic ab-sorption spectrometry. In comparisonwith the control values, the content ofvanadium increased slightly after 1week and significantly after 4 weeks,and decreased slightly after 12 weeks,without reaching the 1 week values. To avoid ion release, it is necessaryto develop new titanium alloy process-ing or increase the mechanical proper-ties of cp Ti. One solution is nanocrys-talline materials, which can offer veryhigh strength, toughness, and fatigueresistance. Processing of nanomateri-als to improve both strength and ductil-ity is of primary importance for fatiguestrength and fracture toughness. R.Z.Valiev et al.5 refined the microstructureof bulk billets using severe plastic de-formation and increased the mechani-cal properties of titanium grade 2.

Ultrafine Grain Titanium in Dental Implants

As described, some dental implantsmade with Ti-6Al-4V can release ionsto tissues locally and systemically. Forstronger implants, though, alloyed ti-tanium is preferred over unalloyed.However, biomechanically the cp Tiimplants have significantly higher re-moval torque than the alloy implants.2

I. Semenova et al.6 showed that ul-trafine grain cp Ti presents ultimatetensile strength as high as 1,240 MPawhile retaining a ductility of 11%. The present work analyzed the pos-sibility of using ultrafine grain titaniumin dentistry. Screw-shaped dental im-plants with pitch-height of 0.5 mm,outer diameter of 3.3 mm, length of 8.0mm, a square head, and inner threadedhole of 2.0 mm were turned from tita-nium rods. Two types of dental implantscrews were used: cp Ti ASTM grade 2and ultrafine grain titanium grade 2. The implants were inserted in thetibiae of New Zealand white rabbits.Bone tissue responses were evaluatedby removal torque tests that were un-dertaken after 8 weeks. Table II showsthe removal torque results. Descriptivestatistical parameters were calculatedand a one-way analysis of variancewith Tukey’s test was used to evaluatethe removal torque. No statistical dif-ference was observed between cp Tiand ultrafine grain titanium.

Mini-Implants for Orthodontic Anchorage

Another dentistry implant is a tem-porary orthodontic mini-implant usedgenerally to secure anchorage in con-temporary orthodontic treatments(Figure 4). This implant has a smalldiameter (1.2 mm to 2.0 mm) and theorthodontic load can deform the mini-implant. Consequently, the orthodonticimplants are made with Ti-6Al-4V in-stead of cp Ti due to the alloy’s supe-rior strength. However, the Ti-6Al-4Vcorrosion resistance is lower than thatof cp Ti, allowing for metal ion release.This implant does not result in osseoin-tegration.

Figure 2. Dental implant components.

Figure 4. An example of an orthodontic mini-implant for anchorage application. (Courtesy of Flavia Rabello.)

Figure 3. A dental implant with good wettability.

2008 March • JOM 49www.tms.org/jom.html

Morais et al.4 inserted mini-implantorthodontics in two groups of rabbits.One group was loaded immediatelyafter the surgery and the second groupwas not loaded during the healing time.When a stress analysis on the mini-implant was carried out, the torque atwhich cp Ti and Ti-6Al-4V deformplastically and the shear strength of theinterface mini-implant-bone was calcu-lated. No increase was observed in theremoval torque value between 1 and 4weeks of healing, regardless of the load.Nevertheless, after 12 weeks, a signifi-cant improvement was observed in bothgroups, with the highest removal torquevalue for the unloaded group. Thestress analysis reveals that the removaltorques for cp Ti dangerously approachits yield stress. The results of this rab-bit model study indicate that titaniumalloy mini-implants can be loaded im-mediately with no compromise in theirstability. The detected concentration ofvanadium did not reach toxic levels inthe animal model. Consequently, to im-prove the mini-implant orthodontic foranchorage behavior it is important to

increase the titanium alloy mechanicalproperties or use cp Ti with ultra-finegrains.

Zygomatic Fixture

The third dentistry implant groupis the zygomatic implants, which aremade of cp Ti (Figure 5). There are some technical approachesto the treatment of the atrophic maxillainvolving a series of clinical consider-ations and producing different results.The development of the zygomatic im-plant (Nobel Biocare, Göteborg, Swe-den) represents an excellent alternativefor these situations. The zygomaticimplant developed by P.-I. Brånemark7

has been used as posterior anchoragefor implant-supported prostheses inpatients with atrophic maxillae since1990. It was initially conceived as atreatment for the victims of traumas ortumor resection where there was con-siderable loss of maxillary structure.Following maxillectomy, many pa-tients retain anchorage regions only inthe body of the zygoma or in the frontalextension of the zygomatic bone. Con-

sequently, a modification to the form ofthe implants is necessary, making theimplants longer than conventional den-tal implants. Normally, the zygomaticimplant has a diameter equal to 4–5 mmand 30–53 mm length. It penetrates themaxilla at the second premolar regionas close to the alveolar crest as pos-sible.8

References

1. C.B. Johansson, “On Tissue Reactions to Metal Implants” (PhD thesis, Dept. of Biomaterials/Handicap Research, University of Göteborg, Sweden, 1991).2. C.B Johansson et al., “Quantitative Comparison of Machined Commercially Pure Ti and Ti-6Al-4V Implant in Rabbit,” J. Oral Maxillofac. Implants, 13 (1998), p. 315.3. P.-I. Brånemark et al., “Osseointegrated Titanium Fixtures in the Treatment of Edentulousness,” Biomaterials, 4 (1983), pp. 25–28.4. Liliane S. Morais et al., “Titanium Alloy Mini-Implants for Orthodontic Anchorage: Immediate Loading and Metal Ion Release,” Acta Biomaterialia, 3 (3) (2007), pp. 331–339.5. R.Z. Valiev, R.K. Islamgaliev, and I.V. Alexandrov, “Bulk Nanostructured Materials from Severe Plastic Deformation,” Prog. Mater. Sci., 45 (2000), p. 103. 6. I. Semenova et al., “Superplasticity in Ultrafine-Grained Titanium: Observations and Properties Studies” (Presentation at the Structural Materials Division Symposium: Mechanical Behavior of Nanostructured Materials, in Honor of Carl Koch: Poster Session: Mechanical Properties of Nanostructured Materials, TMS 2007 Annual Meeting & Exhibition, Orlando, FL, February 25–March 1, 2007).7. S.M. Parel et al., “Remote Implant Anchorage for the Rehabilitation of Maxillary Defects,” J. Prosthet. Dent.,86 (2001), p. 377.8. L.R. Duarte et al., “The Establishment of a Protocol for the Total Rehabilitation of Atrophic Maxillae Employing Four Zygomatic Fixtures in an Immediate Loading System—A 30-Month Clinical and Radiographic Follow-Up,” Clinical Implant Dentistry and Related Research, 9 (4) (2007), p. 186.

C.N. Elias and J.H.C. Lima are with the Biomaterials Laboratory, Instituto Militar de Engenharia, Rio de Janeiro, Brazil. R. Valiev is with UFA State Aviation Technical University, Ufa, Russia. M.A. Meyers iswith the Department of Mechanical and Aerospace Engineering, University of California at San Diego, San Diego, California. Dr. Elias can be reached at elias@ime.eb.br.

Figure 5. A zigomatic implant. (Courtesy of P. Saad.)