Nitinol Biocompatibility
Encyclopedia
Metal implants containing a combination of biocompatible metals or used in conjunction with other biomaterials are often considered the standard for many implant types. When materials are introduced to the body it is important not only that the material does not damage the body, but also that the environment of the body does not damage the implant. One method that prevents the negative effects resulting from this interaction is called passivation
. Passivation is a process that removes corrosive implant elements from the implant-body interface and creates an oxide layer on the surface of the implant. The process is very important for making biomaterials more biocompatible. The following investigation will examine passivation as it relates to NiTi
, nitinol, a commonly used biomaterial especially in the development of stent technology.
Nitinol, which is formed by alloying nickel
and titanium
(~ 50% Ni), is a shape memory alloy
with superelastic properties much similar to that of bone in comparison to that of stainless steel
(another commonly used biomaterial). This property makes nitinol an especially advantageous material for biomedical applications. Some of the biomedical applications that utilize nitinol, include stents, heart valve tools, bone anchors, staples, septal defect devices and implants.
layer mostly composed of TiO2. This process occurs spontaneously as the enthalpy of formation of TiO2 is negative. In alloys, such as nitinol, the formation of an oxide layer protects against corrosion but also removes Ni atoms from the surface of the material. Removing certain elements from the surface of materials is another form of passivation. In nitinol the removal of Ni is important, because Ni is toxic if leached into the body. Stainless steel is commonly passivated by the removal of iron from the surface through the use of acids and heat. Nitric acid is commonly used as a mild oxidant to create the thin oxide film on the surface of materials that protects against corrosion.
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removes many surface impurities and crystal structure breaks that may promote corrosion. Electropolishing
is even more effective, because it doesn’t leave the scratches that mechanical polishing will. Electropolishing is accomplished by creating electrochemical cell
s where the material of interest is used as the anode
. The surface will have jagged qualities where certain points are higher than others. In this cell the current density will be higher at the higher points and cause those points dissolve at a higher rate than the lower points, thus smoothing the surface. Crystal lattice point impurities
will also be removed as the current will force these high-energy impurities to dissolve from the surface.
have been used to improve biocompatibility, but have seen limited success. Coating materials with biologically similar molecules has seen much better success. For example, phosphorylcholine
surface modified stents have exhibited reduced thrombogenic activity. Passivation is an extremely important area of research for biomedical applications, as the body is a harsh environment for materials and materials can damage the body through leaching and corrosion. All of the above passivation methods have been used in the development of nitinol biomaterials to produce the most biocompatible implants.
The decrease in nickel concentration in the surface layer of nitinol is correlated with a greater corrosion resistance. A potentiodynamic test
is commonly employed to measure a material’s resistance to corrosion. This test determines the electrical potential at which a material begins to corrode. The measurement is called the pitting or breakdown potential.
After passivation in a nitric acid solution, Nitinol stent components showed significantly higher breakdown potentials than those that were unpassivated. In fact, there are many surface treatments that can greatly enhance the breakdown potentials of Nitinol. These treatments include mechanical polishing, electropolishing, and chemical treatments such as, Nitric Oxide submersion, etching of the raw surface oxide layer, and pickling to break down bulk material near the surface.
Thrombogenicity
, a material’s tendency to induce clot formation, is an important factor that determines the biocompatibility of any biomaterial that comes into contact with the bloodstream. There are two proteins, fibrinogen
and albumin
, that first adsorb to the surface of a foreign object in contact with blood. It has been suggested that fibrinogen may cause platelet activation due to a breakdown of the protein structure as it interacts with high energy grain boundaries on certain surfaces. Albumin on the other hand, inhibits platelet activation. This implies that there are two mechanisms which can help lower thrombogenicity, an amorphous surface layer where there will be no grain boundary interactions with fibrinogen, and a surface with a higher affinity to albumin than fibrinogen.
Just as thrombogenicity is important in determining suitability of other biomaterials, it is equally important with Nitinol as a stent material. Currently, when stents are implanted, the patient receives antiaggregant therapy for a year or more in order to prevent the formation of a clot near the stent. By the time the drug therapy has ceased, ideally, a layer of endothelial cells, which line the inside of blood vessels would coat the outside of the stent. The stent is effectively integrated into the surrounding tissue and no longer in direct contact with the blood. There have been many attempts made using surface treatments to create stents that are more biocompatible and less thrombogenic, in an attempt to reduce the need for extensive antiplatelet therapy. Surface layers that are higher in nickel concentration cause less clotting due to albumin’s affinity to nickel. This is opposite of the surface layer characteristics that increase corrosion resistance. In vitro tests use indicators of thrombosis, such as platelet, Tyrosine aminotransferase
, and β-TG levels. Surface treatments that have to some extent, lowered thrombogenicity in vitro are:
Another area of research involves binding various pharmaceutical agents such as heparin to the surface of the stent. These drug-eluting stent
s show promise in further reducing thrombogenicity while not compromising corrosion resistance.
Because implanted devices contact the surface of the material, surface science plays an integral role in research aimed at enhancing biocompatibility, and in the development of new biomaterials. The development and improvement of nitinol as an implant material, from characterizing and improving the oxide layer to developing coatings, has been based largely on surface science.
Research is underway to produce better, more biocompatible, coatings. This research involves producing a coating that is very much like biologic material in order to further lessen the foreign body reaction. Biocomposite
coatings containing cells or protein coatings are being explored for use with nitinol as well as many other biomaterials.
Passivation
Passivation is the process of making a material "passive", and thus less reactive with surrounding air, water, or other gases or liquids. The goal is to inhibit corrosion, whether for structural or cosmetic reasons. Passivation of metals is usually achieved by the deposition of a layer of oxide...
. Passivation is a process that removes corrosive implant elements from the implant-body interface and creates an oxide layer on the surface of the implant. The process is very important for making biomaterials more biocompatible. The following investigation will examine passivation as it relates to NiTi
Niti
Niti can refer to:* Nickel titanium alloy or Nitinol* Shape memory alloy* NITI, a Bulgarian UAV...
, nitinol, a commonly used biomaterial especially in the development of stent technology.
Nitinol, which is formed by alloying nickel
Nickel
Nickel is a chemical element with the chemical symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel belongs to the transition metals and is hard and ductile...
and titanium
Titanium
Titanium is a chemical element with the symbol Ti and atomic number 22. It has a low density and is a strong, lustrous, corrosion-resistant transition metal with a silver color....
(~ 50% Ni), is a shape memory alloy
Shape memory alloy
A shape-memory alloy is an alloy that "remembers" its original, cold-forged shape: returning the pre-deformed shape by heating. This material is a lightweight, solid-state alternative to conventional actuators such as hydraulic, pneumatic, and motor-based systems...
with superelastic properties much similar to that of bone in comparison to that of stainless steel
Stainless steel
In metallurgy, stainless steel, also known as inox steel or inox from French "inoxydable", is defined as a steel alloy with a minimum of 10.5 or 11% chromium content by mass....
(another commonly used biomaterial). This property makes nitinol an especially advantageous material for biomedical applications. Some of the biomedical applications that utilize nitinol, include stents, heart valve tools, bone anchors, staples, septal defect devices and implants.
Overview of common passivation methods
In general, passivation is considered to be a process that creates a non-reactive layer at the surface of materials, such that the material may be protected from damage caused by the environment. Passivation can be accomplished through many mechanisms. Passive layers can be made through the assembly of monolayers through polymer grafting. Often, for corrosion protection, passive layers are created through the formation of oxide or nitride layers at the surface.Oxide films
Passivation often occurs naturally in some metals like titanium, a metal that often forms an oxideOxide
An oxide is a chemical compound that contains at least one oxygen atom in its chemical formula. Metal oxides typically contain an anion of oxygen in the oxidation state of −2....
layer mostly composed of TiO2. This process occurs spontaneously as the enthalpy of formation of TiO2 is negative. In alloys, such as nitinol, the formation of an oxide layer protects against corrosion but also removes Ni atoms from the surface of the material. Removing certain elements from the surface of materials is another form of passivation. In nitinol the removal of Ni is important, because Ni is toxic if leached into the body. Stainless steel is commonly passivated by the removal of iron from the surface through the use of acids and heat. Nitric acid is commonly used as a mild oxidant to create the thin oxide film on the surface of materials that protects against corrosion.
]]
Electropolishing
Another mode of passivation involves polishing. Mechanical polishingPolishing
Polishing is the process of creating a smooth and shiny surface by rubbing it or using a chemical action, leaving a surface with a significant specular reflection In some materials polishing is also able to reduce diffuse reflection to...
removes many surface impurities and crystal structure breaks that may promote corrosion. Electropolishing
Electropolishing
Electropolishing, also known as electrochemical polishing or electrolytic polishing , is an electrochemical process that removes material from a metallic workpiece. It is used to polish, passivate, and deburr metal parts. It is often described as the reverse of electroplating...
is even more effective, because it doesn’t leave the scratches that mechanical polishing will. Electropolishing is accomplished by creating electrochemical cell
Electrochemical cell
An electrochemical cell is a device capable of either deriving electrical energy from chemical reactions, or facilitating chemical reactions through the introduction of electrical energy. A common example of an electrochemical cell is a standard 1.5-volt "battery"...
s where the material of interest is used as the anode
Anode
An anode is an electrode through which electric current flows into a polarized electrical device. Mnemonic: ACID ....
. The surface will have jagged qualities where certain points are higher than others. In this cell the current density will be higher at the higher points and cause those points dissolve at a higher rate than the lower points, thus smoothing the surface. Crystal lattice point impurities
Crystallographic defect
Crystalline solids exhibit a periodic crystal structure. The positions of atoms or molecules occur on repeating fixed distances, determined by the unit cell parameters. However, the arrangement of atom or molecules in most crystalline materials is not perfect...
will also be removed as the current will force these high-energy impurities to dissolve from the surface.
Coatings
Another commonly used method of passivation is accomplished through coating the material with polymer layers. Layers composed of polyurethanePolyurethane
A polyurethane is any polymer composed of a chain of organic units joined by carbamate links. Polyurethane polymers are formed through step-growth polymerization, by reacting a monomer with another monomer in the presence of a catalyst.Polyurethanes are...
have been used to improve biocompatibility, but have seen limited success. Coating materials with biologically similar molecules has seen much better success. For example, phosphorylcholine
Phosphorylcholine
Phosphorylcholine is a zwitterionic phospholipid found on the outer surface of red blood cell membranes. It is created by CD5+/B-1 B cells and is referred to as a non-pathogenic autoantibody.-Thrombus Resistant Stents:...
surface modified stents have exhibited reduced thrombogenic activity. Passivation is an extremely important area of research for biomedical applications, as the body is a harsh environment for materials and materials can damage the body through leaching and corrosion. All of the above passivation methods have been used in the development of nitinol biomaterials to produce the most biocompatible implants.
Influence of surface passivation on biocompatibility
Surface passivation techniques can greatly increase the corrosion resistance of nitinol. In order for nitinol to have the desired superelastic and shape memory properties, heat treatment is required. After heat treatment, the surface oxide layer contains a larger concentration of nickel in the form of NiO2 and NiO. This increase in nickel has been attributed to the diffusion of nickel out of the bulk material and into the surface layer during elevated temperature treatments. Surface characterization methods have shown that some surface passivation treatments decrease the concentration of NiO2 and NiO within the surface layer, leaving a higher concentration of the more stable TiO2 than in raw, heat-treated Nitinol.The decrease in nickel concentration in the surface layer of nitinol is correlated with a greater corrosion resistance. A potentiodynamic test
Cyclic voltammetry
Cyclic voltammetry or CV is a type of potentiodynamic electrochemical measurement. In a cyclic voltammetry experiment the working electrode potential is ramped linearly versus time like linear sweep voltammetry. Cyclic voltammetry takes the experiment a step further than linear sweep voltammetry...
is commonly employed to measure a material’s resistance to corrosion. This test determines the electrical potential at which a material begins to corrode. The measurement is called the pitting or breakdown potential.
Breakdown voltage
The breakdown voltage of an insulator is the minimum voltage that causes a portion of an insulator to become electrically conductive.The breakdown voltage of a diode is the minimum reverse voltage to make the diode conduct in reverse...
After passivation in a nitric acid solution, Nitinol stent components showed significantly higher breakdown potentials than those that were unpassivated. In fact, there are many surface treatments that can greatly enhance the breakdown potentials of Nitinol. These treatments include mechanical polishing, electropolishing, and chemical treatments such as, Nitric Oxide submersion, etching of the raw surface oxide layer, and pickling to break down bulk material near the surface.
Thrombogenicity
Thrombogenicity
Thrombogenicity refers to the tendency of a material in contact with the blood to produce a thrombus, or clot. It not only refers to fixed thrombi but also to emboli, thrombi which have become detached and travel through the bloodstream. Thrombogenicity can also encompass events such as the...
, a material’s tendency to induce clot formation, is an important factor that determines the biocompatibility of any biomaterial that comes into contact with the bloodstream. There are two proteins, fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
and albumin
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
, that first adsorb to the surface of a foreign object in contact with blood. It has been suggested that fibrinogen may cause platelet activation due to a breakdown of the protein structure as it interacts with high energy grain boundaries on certain surfaces. Albumin on the other hand, inhibits platelet activation. This implies that there are two mechanisms which can help lower thrombogenicity, an amorphous surface layer where there will be no grain boundary interactions with fibrinogen, and a surface with a higher affinity to albumin than fibrinogen.
Just as thrombogenicity is important in determining suitability of other biomaterials, it is equally important with Nitinol as a stent material. Currently, when stents are implanted, the patient receives antiaggregant therapy for a year or more in order to prevent the formation of a clot near the stent. By the time the drug therapy has ceased, ideally, a layer of endothelial cells, which line the inside of blood vessels would coat the outside of the stent. The stent is effectively integrated into the surrounding tissue and no longer in direct contact with the blood. There have been many attempts made using surface treatments to create stents that are more biocompatible and less thrombogenic, in an attempt to reduce the need for extensive antiplatelet therapy. Surface layers that are higher in nickel concentration cause less clotting due to albumin’s affinity to nickel. This is opposite of the surface layer characteristics that increase corrosion resistance. In vitro tests use indicators of thrombosis, such as platelet, Tyrosine aminotransferase
Tyrosine aminotransferase
Tyrosine aminotransferase is an enzyme present in the liver and catalyzes the conversion of tyrosine to 4-hydroxyphenylpyruvate. In humans, the tyrosine aminotransferase protein is encoded by the TAT gene...
, and β-TG levels. Surface treatments that have to some extent, lowered thrombogenicity in vitro are:
- Electropolishing
- Sandblasting
- Polyurethane coatings
- Aluminum coatings
Another area of research involves binding various pharmaceutical agents such as heparin to the surface of the stent. These drug-eluting stent
Drug-eluting stent
A drug-eluting stent ' is a peripheral or coronary stent placed into narrowed, diseased peripheral or coronary arteries that slowly releases a drug to block cell proliferation. This prevents fibrosis that, together with clots , could otherwise block the stented artery, a process called restenosis...
s show promise in further reducing thrombogenicity while not compromising corrosion resistance.
Welding
New advances with micro laser welding have vastly improved the quality of medical devices made with nitinol.Remarks
Nitinol is an important alloy for use in medical devices, due to its exceptional biocompatibility, especially in the areas of corrosion resistance and thrombogenicity. Corrosion resistance is enhanced through methods that produce a uniform titanium dioxide layer on the surface with very few defects and impurities. Thrombogenicity is lowered on nitinol surfaces that contain nickel, so processes that retain nickel oxides in the surface layer are beneficial. The use of coatings has also been shown to greatly improve biocompatibility.Because implanted devices contact the surface of the material, surface science plays an integral role in research aimed at enhancing biocompatibility, and in the development of new biomaterials. The development and improvement of nitinol as an implant material, from characterizing and improving the oxide layer to developing coatings, has been based largely on surface science.
Research is underway to produce better, more biocompatible, coatings. This research involves producing a coating that is very much like biologic material in order to further lessen the foreign body reaction. Biocomposite
Biocomposite
A biocomposite is a material formed by a matrix and a reinforcement of natural fibers . With wide-ranging uses from environment-friendly biodegradable composites to biomedical composites for drug/gene delivery, tissue engineering applications and cosmetic orthodontics...
coatings containing cells or protein coatings are being explored for use with nitinol as well as many other biomaterials.
Current research/further reading
- The U.S. Food and Drug Administration lists recently approved stent technology on their Heart Health Online site.
- Angioplasty.org contains information on current stent research, as well as other issues relating to the circulatory systemCirculatory systemThe circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
. Including:- Drug-eluting Stents
- Current developments in stent technology.
- Advancements in circulatory imaging technology.
- Use of biocomposites for medical applications:
- ISO and FDA set standards for evaluationg and determining biocompatibility. ISO 10993 Standards-"Biological Evaluation of Medical Devices"