1. Introduction
Nitinol is a ‘smart’ alloy that exhibits dual unique properties of superelasticity and shape memory combined with excellent biocompatibility. Comprised generally of near equal components of the transition metals, nickel (Ni) and titanium (Ti) NiTi, Nitinol’s excellent malleability and ductility allow it to be manufactured in the form of wires, ribbons, tubes, sheets, or bars, thereby providing a wide spectrum of opportunities for medical applications, Nitinol has profoundly impacted medical device design in recent years [1,2]. Metallic alloys that return to the original shape (Smart Memory Alloys – SMAs) after large stress or deformations have been appreciated since the 1950s. In addition to their extensive use in Aeronautical and Aerospace Engineering, they have also been investigated for their use in Medicine in the development of prostheses that substitute long bones and in the study of surfaces and biofilms [3,4]. The behaviour of Nitinol can be altered by modifying the composition or porosity and applying external mechanical and thermal treatment. The superelasticity of Nitinol refers to the capacity of the material to accommodate substantial recoverable strains within a given temperature range. Shape memory of Nitinol refers to the capacity of the material to deform at a given temperature and recover to its original shape upon heating above its transformation temperature. These dual unique properties of Nitinol, along with its excellent biocompatibility, make the material an attractive option for self-expanding TAVI (Transcatheter Aortic Valve Implantation) braced with Nitinol stents, orthopedic implants, ortho- and endodontics and other medical devices including Medtronic’s new to market Micra pacemaker to name a few, as seen in Figure 1 [1].
Figure 1: The self-expanding TAVI Nitinol-braced stent, orthodontic ‘braces’ including wires and brackets made from Nitinol and Medtronic Micra pacemaker with Nitinol ‘anchors’.
2. Chemical Structure and Physical Form
Nitinol alloys (NiTi) consist of a roughly equiatomic composition of the transition metals Nickel and Titanium (50/50), this fraction can be altered for example, Nitinol 55 and Nitinol 60 represent 45 and 40%wt Titanium, respectively. Titanium is the fourth most abundant metal on the earth’s crust and has a similar strength to steel but weighs around half of that of steel [5,6]. Additionally, it is noted that adding an additional Nickel up to an extra 1% (in 50/50 compositions) increases the yield strength of the austenitic phase while at the same time depressing the transformation temperature. Nitinol is an alloy and has the structure of a metal, meaning that there are no specific nickel-titanium bonds, as can be confused from diagrams representing the crystal lattice structure. The properties of Nitinol depend upon this heat sensitive crystalline structure. In normal metals, deformations cause the relocation of the molecular structure into new crystal positions. There is no ’memory’ in the crystal of where the atoms were before they moved. The physical movement capabilities of Nitinol are attributed to internal molecular restructuring. To view this variation in properties, DSC data shown in Figure 2 describes the change in lattice structure in response to cooling and heating, which is further described in 2a (i) and Figure 3.
Figure 2: DCS curve for a Nitinol SMA, used to determine the phase transformation temperatures of the alloy. The temperature points indicated are ones frequently used to describe the behaviour of a particular alloy. Ms – Martensite starts to form on cooling, Mf – Martensite finishes; As – Austenite starts to form on heating, Af – Austenite finishes. Mp and Ap marks the Martensite and Austenite point. Ref: Johnson Matthey Medical Components (http://jmmedical.com/resources/211/Measuring-Transformation-Temperatures-in-Nitinol-Alloys.html).
3. Nitinol Fundamentals
(i) Phase Transformation
Nitinol’s unique characteristics (shape memory and superelasticity) are derived from its ability to undergo reversible phase transformation. Upon the application of stress or temperature or a combination of both to Nitinol, it will undergo phase transformation between Austenite and Martensite as seen below in Figure 3 (a) and (b) [1]. The “daughter” phase of Nitinol, known as Martensite, the crystal structure is aligned and cubic, this phase is obtained at low temperatures or high strains. The “parent” phase of Nitinol that is stable at high temperatures is known as Austenite. Martensitic Nitinol is highly malleable when compared to austenite [1,7].
Figure 3: (a) Molecular views of Nitinol in its natural state (Martensitic) and of Nitinol subjected to heat (Austenitic). (b) Hand-drawn view in schematic form of the shape memory effect including transitions between phases, from Kapoor, 2017 [7,8].
(ii) Superelasticity
In the case that Nitinol phase transformation is driven by an externally applied force or stress slightly above its transformation temperature, it is called superelasticity. This effect is caused by the external stress-induced formation of some martensite above its normal temperature from austenite. Upon discharge of the load, martensite will revert immediately back to its parent or austenite phase [1], this can be seen in Figure 4 (a) and (b). Nitinol’s superelasticity is characterised by a variation in the loafing and unloading curve during the application of a force or load. Nitinol can facilitate strains up to 10% in some cases and still revert back to its original shape following removal of the load. Commonly used medical devices composed of alloys and metals for example, Stainless Steel, can usually facilitate strain levels of less than 2% (as low as 1% according to Melzer, 2010 [9]). Nitinol exhibits a different behaviour in terms of stress hysteresis, while in most engineering materials, stress increases linearly with strain upon loading and decreases along the same path upon unloading. Following an initial linear increase in stress with strain, large strains can be obtained with a small further stress increase (The loading plateau; which is reached around 8% strain). Unloading from the end of the plateau region, results in the stress decreasing quickly until a lower plateau (The unloading plateau) is reached. Strain is recovered in this unloading region with only a small decrease in stress, with the last portion of the deforming strain finally recovering in a linear fashion, this can be visualised in Figure 4 (b) [1,9,10].
Figure 4: (a) Hand-drawn Stress-Strain graph. A (stainless steel behaviour), B (stabilized martensitic wire (E.g. Nitinol)) & C (represents superelastic wire): wires present different stiffness [3]. (b) Hand-drawn Stress-Strain graph representing a typical curve for a superelastic alloy, forming plateaus during loading and unloading. Transitions from Austenite to Martensite and back again are shown on respective plateaus [1,3].
(iii) Shape Memory
When Nitinol is in its martensitic form, it is easily deformed to a new shape. However, when Nitinol transformation is driven by a change in temperature, it reverts to austenite and recovers its prior shape with large force. This is considered the process of Shape Memory. Decreasing the temperature below a certain point (specifically the Ms) results in the formation of martensite, resulting in Nitinol being more malleable. The specific temperature at which Nitinol ‘remembers’ its high temperature form when heated can be adjusted by minor changes in the alloy composition and through heat treatment. Such drastic changes can even be carried out manipulating the transition temperature from above 100C to below -100C [1,3].
In order for shape memory to be realized, shape setting is a well understood procedure carried out by engineers to form a NiTi component into the desired shape for a particular application. Shape setting si conventionally performed by beginning with a cold worked material and exposing the NiTi elements to high temperatures ~500 °C for around 5 minutes. Rapid cooling of some form is required via a water quench or rapid air cool. This heat treatment and constraint allows for not only the austenite shape to be memorized but also the functional properties are set as required. This can be difficult as cold worked materials can be difficult to insert into fixtures, bend to desired shapes and some materials break in fixtures [11].
According to various sources, Nitinol possesses the following characteristics in most cases:
- Density – 6.45 g/cm3
- Young’s Modulus – Austenite Approx. 83GPa | Martensite Approx 28-41GPa
- Melting Point – 1,200-1,300C
- Ultimate Tensile Strength – Fully annealed 895 MPa | Work Hardened 1900MPa
4. Function
Shape Memory Alloys combine favourable mechanical properties with thermal shape memory and have been used extensively throughout the past 70/80 years in non-medical applications for example in Aerospace engineering [12]. Biomedical applications of SMA have become extremely common and successful due to the functional properties of these alloys increasing both the possibility and performance of minimally invasive surgeries [2]. SMA have been used extensively in biomedical applications, including Cardiovascular, Orthopedic and their varying use in surgical instruments. Nitinol alloys comprise products offered by most medical device companies including self-expanding stents, vascular filters, graft support systems, heart valve frames, occlusion devices, and various other devices for minimally invasive interventional and endoscopic procedures [9]. Considering some of the examples mentioned above:
Self-expanding stents represent one of the largest volume manufactured products composed of Nitinol with the aim of improving the treatment of peripheral vascular disease. The stents are manufactured to a size marginally above the diameter of the vessel. The stent is crimped and constrained in a delivery catheter, whereby at the treatment site the constraint is removed and the stent expands elastically until it comes into contact with the vessel wall, where it continues to exert a small outward force, thereby re-opening the vessel [9]. Nitinol stents have evolved and take various shapes and configurations of ‘struts’, various designs can be seen in Figure 5 (a).
Vena Cava filters are used for patients at risk of pulmonary embolism (PE). The filters are designed to catch hazardous blood clots as a result of surgery, trauma, or other medical conditions before they can reach the lungs, which would in turn result in a PE. A market leader in this is the TrapEase filter (Cordis), which employs a “double basket” that can be delivered via jugular, femoral or antecubital approaches. The design itself, consists of laser cut Nitinol tube and expanded to its operating shape, it may be seen below in Figure 5 (b) [9].
Figure 5: (a) Today’s stents employ variations of the original basic design features introduced by the SMART stent (Cordis) in 1998. (b) Vena cava filter, TheTrapEase (Cordis) is composed of a monolithic structure which was laser cut from a Nitinol tube and expanded [9].
5. Biocompatibility
Biocompatibility is the ability of a given material to remain biologically innocuous, resulting in a preferred host response, throughout its functional time inside a living organism [2,13]. Nitinol is a ‘smart’ alloy that exhibits dual unique properties of superelasticity and shape memory combined with excellent biocompatibility. The usefulness of a material in terms of biocompatibility can be established on the base of three selection criteria chemical, biological and mechanical reactions, with additional factors of corrosion resistance, great capability of absorption of vibration (due to the easiness of the displacement of the internal interfaces of these alloys), the capacity to convert the heat energy in mechanical energy, and so on [2].
High acidity of certain bodily fluids is particularly hostile for metallic implants.
It is of utmost importance to understand the direct effects of an individual component of the alloy since it may dissolve in the body due to corrosion and it can cause local and systemic toxicity, carcinogenic effects and immune response. The cytotoxicity of elementary nickel and titanium has been widely researched, especially in the case of nickel, which is a highly poisonous element and allergen [2]. Nickel is known to have toxic effects on soft tissue structures at high concentrations and also appears to be harmful to bone structures, but substantially less than cobalt or vanadium, which are also routinely used in implant alloys. Some studies have shown that persons have prolonged contact with nickel express problems such as pneumonia, nostril and lung cancer, to name a few. Experiments with toxic metal salts in cell cultures have shown decreasing toxicity in the following order: Co > V > Ni > Cr > Ti > Fe. Conversely, titanium is recognized to be one of the most biocompatible materials due to the ability to form a stable innocuous titanium oxide layer, which surrounds the surface. This layer is responsible for the high resistance to corrosion exhibited by titanium alloys. In an optimal situation, it is capable of excellent osteointegration with the bone and it is able to form a calcium phosphate-rich layer on its surface, which can be seen in Figure 6, very similar to hydroxyapatite which also prevents corrosion [10]. Another advantageous property is that in case of damaging the protective layer the titanium oxides and calcium phosphate layer regenerate. Nitinol’s resistance to corrosion has been noted to be higher than that of stainless steel [2,13].
Figure 6: The formation of a hydroxyapatite layer on a Titanium oxide film as described by Brojan, M. et al. [10].
An aggressive corrosion environment is continuously present for all implants once they are introduced to the body’s complex electrochemical system, which are surrounded by fluids present in the body of an aerated solution containing 0.9% NaCl, with small amounts of other salts, organic compounds, proteins, cells and serum ions, which all may affect the local corrosion effect. The acidity may increase locally in the area surrounding an implant due to the body’s inflammatory response of surrounding tissues for example mediating hydrogen peroxide and reactive oxygen and nitrogen compounds, a change in acidity may alter biological or chemical processes around the implant [10].
In terms of protein adsorption onto biomaterial surfaces, various surface properties including chemical composition, crystallinity, roughness and wettability influence this and subsequent cell adhesion [10]. Some studies show that naturally blood plasma proteins such as Albumin for example will be detected on all samples of Nitinol wire [14,15]. Surface characteristics such as hydrophobicity and surface roughness were shown to have little to no effect on albumin absorption onto Nitinol surfaces [14]. As mentioned earlier, the importance of the Ni and Ti composition, there was a straightforward correlation between the surface nickel and oxygen concentration and the subsequent amount of albumin absorbed. Clarke et al. showed that samples exhibiting higher levels of Ni and less oxygen in the surface oxide layer of the NiTi wires showed increased albumin adsorption, which led to subsequent improved biocompatibility [14]. Michiardi et al. deduced that protein and albumin adsorption on Nitinol alloys were directly proportional to the polarity and surface energy and inversely proportional to the concentration of Ni in the bulk alloy [15].
Natural structural materials such as hair, tendons and bones may deform elastically by as much as 10% (Figure 8). Superelastic Nitinol behaves in a near identical way to those biological materials listed above; when loaded, it facilitates a large strain without increase in stress, and when unloaded, the strain reduces at a lower but constant stress. Nitinol stress-strain behaviour has been shown to be very similar to that of structures in the human body [7,8].
Figure 8: Hand-drawn interpretation of the graph of Stress-Strain which shows nonlinear behaviour and a charge/discharge cycle with significant hysteresis comparing Nitinol and biological materials including hair, bone and tendon, indicated in the figure [7].
6. Conclusion
Nickel-Titanium alloys have allowed for a major leap forward in evolution for Medicine, going from dealing with Aerospace engineering problems to dealing with current Biomedical problems. Evolving from samples with distinctive martensitic characteristics to the current products with thermoelastic and superelastic properties. The feature of superelasticity and shape memory exhibited by advanced Nitinol materials adds excellent multifunctionality to the design and fabrication of various devices used to treat cardiovascular, various other diseases and remedy orthopedic and surgical complications. Applications of Nitinol to surgery has significantly enhanced both the posibility and success of less invasive surgeries, including for example the self-expansion, dynamic interference and stress hysteresis that make Nitinol stents the significantly preferred treatment for vascular diseases. Corrosion resistance, bio- and biomechanical compatibility, make Nitinol well suited for permanent implants in the vasculature. Therefore, it can be said that smart materials are becoming dominant in the biomedical field. Unfortunately, the undesired characteristic of biocompatibility of nickel is one of the most critical points concerning the spreading use of Ni-Ti alloys. As mentioned earlier, Ni is a poisonous substance and can cause a multitude of adverse/allergenic effects on humans and therefore Nitinol with a slightly enriched surface Ni concentration that does not exhibit Ni release could have potential as a future medical device material.
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