In this article, we’ll cover:
- Reasons titanium is used in medical implants
- Titanium and biocompatibility
- Titanium for biomedical applications
- Titanium for dental implants
- Surface modifications of dental implants
- Historical achievements in dental implants
- Developing the future of biomaterials
- Three factors successful implants must possess
Why titanium is used in medical implants?
The global demand for safer and more effective materials is greatly increasing in biomedical engineering due to the annual increase of the world’s population, the growing number of older people, and the high functional demands of younger people. A biomaterial and its surrounding physiological environment (like bone or other tissues) have to coexist harmoniously, without rejecting or negatively affecting or influencing one another.
This is the most important requirement of a biomaterial, and its surface properties are the ones which finally determine the integration (acceptance or rejection) in the body.
Looking a little bit into the textbooks on this matter, the multidisciplinary research domain of biomaterials includes various topics from physics, chemistry, engineering, biology, materials science and medicine, to name the most important ones. Biomaterials are special functional materials (metals, alloys, ceramics, etc.) used in various (bio)medical devices, systems and applications. They are used for appraising, improving, treating and/or replacing any function and/or biological part of the body in which they are used .
Titanium (Ti) and Ti-based alloys are regarded as some of the most important biomaterials used to date, due to desirable features like resistance to effects caused by body fluids, high tensile strength, non-ferromagnetic (or ferrimagnetic) properties, flexibility and high resistance to corrosion. This specific combination of strength, low reactivity and biocompatibility , together with versatile surface modification and functionalisation possibilities,  makes them highly suitable for (bio)medical devices and applications.
Titanium and biocompatibility
Because the focus of biomaterials has shifted more towards tissue engineering, complex medical applications and biotechnology, it has become necessary to better define and evaluate the specific interaction between biomaterials and tissues.
Prof. David Williams of the Wake Forest School of Medicine proposed a unified concept of biocompatibility , which states that ‘Biocompatibility refers to the ability of a biomaterial to perform its desired function with respect to medical therapy, without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy, but generating the most appropriate beneficial cellular or tissue response in that specific situation, and optimising the clinically relevant performance of that therapy.’
From this perspective, Ti and its alloys remain essentially unchanged when implanted into the human body, so that such materials are referred to as bio-stable or biologically inert .
Besides artificial bones, joint replacements and dental implants, Ti and Ti-based alloys are also often used in cardiovascular implants, for example in prosthetic heart valves, protective cases for pacemakers, artificial hearts and circulatory devices.
Titanium for biomedical applications
Some alloys like Ni14Ti11 (Nitinol, a well-known shape memory alloy) have received a lot of attention in magnetic resonance imaging (MRI) diagnostic tools. Currently, Nitinol stents are often used in the treatment of cardiovascular disease and are usually coated with a thin film of carbon, in order to enhance blood compatibility .
The clinical goal and most critical factor in the success of bone implants (orthopaedics and dentistry) is to achieve osseointegration, particularly by establishing a strong and long-lasting structural and functional connection between the artificial implant surface and peri-implant living bone, leading to a stable mechanical attachment of the implant at the site of implantation .
Osseointegration is crucial to be achieved as fast as possible, because it assures the successful long-term integration of the implant into the body, without being rejected by it. It’s as if the implant is a foreigner wanting to be part of a family. Through osseointegration, it ‘gains the trust of the family’ and thus becomes an ‘official’ member of it, enjoying all the benefits that come from this union. And the faster he does this, of course, the better.
Therefore, the fate of the implant material is not only governed by the bulk, but also by its surface properties (surface chemistry, morphology and structure), which are crucial factors in the interactions with the surrounding tissues from the body.
Currently, the performances of biomaterials are commonly improved by targeted modifications of the surface properties, either morphologically and/or by biochemical coatings. There is a major need for surface modification of implants in order to increase tissue adhesion and implant integration, decrease bacterial adhesion and inflammatory response, or avoid the foreign body response.
Coming back to dental implants, if you’re a professional working in this industry, or a well-informed patient, customer or scholar, you may have heard about Straumann SLA® (ITI Straumann, Basel, Switzerland), Ankylos® (Dentsply Friadent, Mannheim, Germany), Dentium Superline® (Dentium Co., Seoul, Korea), Genesio® (GC Corporation, Tokyo, Japan), MIS Seven® (MIS Implants Technologies, Bar Lev, Israel) or ActivFluor® (Blue Sky Bio, Grayslake, IL, USA). These are just a few of the commercially available dental implant brands used today by countless people worldwide.
Titanium for dental implants
Nowadays, commercial, chemically pure Ti is the dominant material for dental implants and is used as an alternative to Ag-Pd-Au-Cu alloys. The Ti-based alloys used for the same purposes are Ti-6Al-7Nb, Ti-6Al-4V, Ti-13Cu-4.5Ni, Ti-25Pd-5Cr, Ti-20Cr-0.2Si, etc. .
Roughness modifications of Ti and Ti alloys, although proven to be very effective in improving their (bio)medical performance [7,8], do not alter their bioinert nature and hence further chemical modifications are needed in order to ensure rapid osseointegration.
From simple (e.g. apatite) to complex coatings, a lot of research has been performed both in vitro and in vivo, in order to analyse and evaluate the optimal deposition methods (e.g. plasma spray, electrodeposition, biomimetic precipitation of calcium phosphate by immersion in a simulated body fluid, protein adsorption etc.) and investigate their mechanical properties.
More recent attention is put on biomolecular functionalisation of the implant surface with different (bio)molecules (natural extracellular matrix proteins such as collagen and fibronenctin; peptides; engineered protein fragments etc.). In all cases, however, the critical steps are the actual binding of the bioactive molecule to the implant surface and the selection of the immobilisation method.
Surface modifications of dental implants
A huge amount of research has been performed on surface modifications of micro- and nanorough Ti and Ti implants . If the relatively compact implant surface is replaced with a nanostructured surface or coating (nanotubes, nanorods, etc.), numerous possibilities of structural, morphological and chemical modifications arise and their resulting synergistic effects can lead to significant improvements in the field of tissue engineering.
- The mechanical methods most widely used in obtaining rough or smooth Ti and Ti alloy surfaces and in fabricating nanophase surface layers are subtraction (grinding, polishing, machining, blasting) and attrition processes, respectively [4, 10].
These mechanical modifications aim to produce specific surface topographies or to clean or roughen the surface, which could then lead to improved adhesion in bonding, as the roughness of the structure would be more favourable for biomineralisation due to the increased surface area .
- The chemical methods are used in order to improve biocompatibility, bioactivity and bone conductivity (or osteoconduction, essentially meaning that bone grows on a surface), corrosion resistance and removal of contamination. These methods provide Ti and Ti alloys with bioactive surface characteristics. Some of the most widely used chemical methods are acid and alkaline etching, electrochemical anodization, chemical deposition and biochemical surface coating methods [4,8,12].
- Physical surface modification methods [4,8,12] include thermal spraying, physical vapour deposition, ion implantation and glow discharge plasma treatments. For these methods, there are no chemical reactions taking place to produce the desired engineered surface, and the resulting layer/film/coating from the Ti substrate surface is basically a product of the different energy types (thermal, electrical, kinetic) characteristic/specific to each method.
For Ti implants surfaces, irregular nanometric morphologies can be easily established through various chemical methods. On the other hand, in order to produce controlled, “symmetric” nanostructures (nanodots, nanotubes or nanorods), electrochemical anodization of Ti is one of the most popular methods used. Further functionalization of the Ti implants surfaces is possible in both cases, afterwards, if necessary.
The recent developments in the production of nanostructured Ti and Ti oxides surfaces and the mechanisms which take part in Ti anodization can be consulted in the latest reviews by Roy et al.  and Kowalski et al. . On the surface of most Ti alloys containing transition metals, such as Ti-6Al-7Nb [15,16], Ti-6Al-4V , Ti-6Al-4Zr and TiZr alloys with different Zr concentrations [17,18], regular TiO2 nanostructures can nowadays be produced rather easily and efficiently.
Historical achievements in dental implants
The early failure of Maggiolo’s design to implant gold tooth roots into fresh extraction sockets in 1809 encouraged some researchers to further investigate and use various metals to replace missing teeth . In the late 1800s, various researchers unsuccessfully attempted to use different metals, including Pt posts coated with Pb, Au, or Ir tubes, Ag capsules etc. . However, it was not until the late 1930s when Venable created a new alloy composition, Vitallium (Co-Cr-Mo alloy), that became the first long-term successful implant material .
While commercially pure Ti and Ti-6Al-4V have been used mostly for fabricating dental implants, wrought stainless steel, Co-Cr-Ni (Elgiloy), β-Ti, and Nitinol alloys are used for making orthodontic wires, in which high yield strength and preferably low elastic modulus provide high “working range” characteristics. The requirement of low elastic modulus favors the selection of β-Ti and NiTi alloys for orthodontic wires, although all four alloys are currently used .
In the late 1900s, Branemark et al.  and Albrektsson et al.  introduced and presented long-term data on the success of dental implants. They reported 90% implant survival over 10-15 years of follow up [23,24]. Since then, the use of dental implants for oral rehabilitation of fully and partially edentulous patients has greatly broadened the scope of clinical dentistry, creating additional treatment options in complex cases in which functional rehabilitation was previously limited or inadequate .
Many different implant systems, varying in body shape, material, surface properties, diameter, length, and interface geometry, have been introduced into the dental market [26,27]. There are more than 100 different implant systems currently available .
Dental implants (i.e., artificial teeth roots) are biocompatible anchors surgically positioned in the jaw bone (i.e., surgically traumatized bone), underneath the gums, to support an artificial crown where natural teeth are missing. Using the root form implants (the closest in shape and size to the natural tooth root), the non-union (due to traumatization) bone healing period usually varies from three months to six months or more.
During this period, osseointegration occurs, and the bone grows in and around the implant creating strong structural support, to which a superstructure will be attached later on by either cementation or by a screw-tightening retaining technique.
At the beginning of the century, it was reported that there were 25 dental implants manufacturers marketing around 100 different dental implant systems, having a variety of diameters, lengths, surfaces, platforms, interfaces, and body shapes . Significant differentiation and distinctions are based on (i) the implant/abutment interface, (ii) the body shape, and (iii) the implant-to-bone surface.
For dental implants, many aspects of biocompatibility profiles have been shown to depend on interrelated biomaterials, tissue and host factors, being associated with surface and bulk properties. In general, the biomaterial surface chemistry (purity and surface tension for wetting), topography (roughness), and type of tissue integration (osseous, fibrous, or mixed) can be correlated with shorter- and longer-term in vivo host responses. Moreover, the host environment has been shown to directly influence the biomaterial-to-tissue interface zone, specific to the local biochemical and biomechanical circumstances of healing and longer-term clinical aspects of a load-bearing function.
The interaction at the interface between recipient tissues and the implanted biomaterial is limited to the surface layer of the implant and a few nanometers inside the living tissues. The details of the interaction (hard or soft tissue) and force transfer that results in static (stability) or dynamic (instability or motion) conditions have also been shown to significantly alter the clinical longevity of intraoral device constructs .
Dental implants are usually classified based on implant design (endosteal–blade, ramus frame and root form–, subperiosteal, transosteal and intramucosal), attachment mechanism (osseointegration and fibro integration), macroscopic body design (cylinder, thread, plateau, perforated, solid and hollow, or vented), surface of the implant (smooth, machined, textured and coated) and type of material (metallic, ceramic and ceramic coated, polymer and carbon compound) .
Developing the future of biomaterials
Selected metals and metal alloys are among the best biomaterials used today, mainly due to their optimal biocompatibility and mechanical properties:
These materials are the most widely used for biomedical applications such as orthopaedic and dental implants.
Because the surface of biomaterials comes in contact and interacts directly with the biological environment, the foremost challenge in improving the implant’s “longevity” and function is the right surface modifications. If the implant material-body tissue interface is correctly designed/engineered, then the implant will be successfully integrated into the body and will perform splendidly.
Understanding better the mechanisms of protein adsorption and cell adhesion at the material-tissue interface will provide researchers with more robust means to select the proper biomaterial and surface modification technique.
Particular surface treatments will have to be adopted based on the materials substrate, the specific biological environment and the given application in order to enhance the in vivo performance.
Soon, it is anticipated that technical breakthroughs in synthetic chemistry, biofunctionalization, micro- and nano-engineering, and surface characterization will lead to the fabrication of even more advanced and bioactive implant surfaces. In particular, surfaces that are highly topographically-complex at the submicron level are thought to interact with certain proteins more effectively and are therefore expected to provide unprecedented control over cellular activities and remarkable healing responses.
3 factors successful implants must possess
A dental implant system is a perfect example of an integrated product using multiple disciplines including surface science and technology (surface modifications and surface physics and chemistry). The success and longevity of dental implants are strongly governed by their surface characteristics.
The particular factors that successful implants must possess to accommodate osseointegration are:
- biological compatibility, i.e., not to be toxic to surrounding hard and soft tissues,
- mechanical compatibility, i.e., to smoothly transfer the stress between the placed implant root and receiving hard tissue,
- morphological compatibility, i.e., to accommodate the surface rugophilicity and promote bone cell growth.
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