Nitinol shape memory alloy has become an ideal in vivo fixation material due to its excellent properties such as good biocompatibility, shape memory effect, and superelasticity. It has been widely used in clinical treatment. Due to the shape memory effect and superelasticity of nitinol shape memory alloy, it can effectively avoid material fracture caused by stress shielding, and it is expected to be stored in the human body for a long time. However, the nickel ions released by corrosion of the alloy in the human body are biologically toxic and have sensitization and even carcinogenic effects on local tissues, which limits its wide clinical application. This paper reviews the literature on the biocompatibility of nitinol shape memory alloys, summarizes the research progress on the biocompatibility of nitinol shape memory alloys in vitro and in animals, and the biocompatibility of clinical applications, and points out the importance of surface treatment of nitinol shape memory alloys in improving their biocompatibility.
Recently, with the development of medical biomaterials science and the needs of clinical medicine, nitinol shape memory alloys have excellent physical and chemical properties such as high strength, wear resistance, corrosion resistance, non-magnetic, and non-toxic because of their shape memory effect. The hardness and stiffness are close to the bone tissue of the human body, and they are considered to be one of the ideal materials for implantable biological fixation, which has been widely used in the medical field. The currently reported application of nitinol shape memory alloys in the medical field involves orthopedics, stomatology, thoracic surgery, obstetrics and gynecology, and imaging disciplines. The products that have been developed include scoliosis hastelloy rods, hip prostheses, frame-type ulnar flexor fixation devices, patella fixation devices, intrauterine contraceptive rings, dental orthodontic filaments and other biomedical materials.
Most biocompatible studies have shown that nitinol shape memory alloys have low cellular and genotoxicity, but nitinol shape memory alloys are potentially toxic to the human body due to the presence of a large amount of nickel, and nickel and its compounds. The presence of excessive nickel ions in the human body often causes local tissue allergic reactions. After nickel ions enter the body fluid circulation, they may also affect amino acid metabolism, protein deterioration, and have adverse effects on the liver and blood system, which in turn leads to teratogenic, carcinogenic and other adverse consequences. Therefore, the safety of nitinol shape memory alloys has always attracted the attention of research scholars. Nitinol shape memory alloys precipitate nickel ions in the human body, and their release is closely related to the roughness and chemical composition of the alloy surface. The release of nickel ions and their toxic effects on the body have also become limiting factors for the application of such alloys. At present, a large number of scholars have cleverly modified the surface of nitinol shape memory alloys in order to improve the biocompatibility of the alloys. This paper intends to review the research progress on the biocompatibility of nitinol shape memory alloys, and review the effects of in vitro cell tests, in vivo animal tests, clinical applications, and surface modifications on their biocompatibility, so as to objectively evaluate the biocompatibility of nitinol shape memory alloys and the necessity of surface treatment to improve their biocompatibility.
The dissolution of nickel ions has attracted much attention during the use of nitinol shape memory alloy implants. Many researchers have monitored the release of nickel ions in nitinol shape memory alloys. For example, in a study of the in vitro solubility of nitinol shape memory alloy bow wire, some researchers found that the average nickel ion release rate was 13.05mg/day, which was significantly lower than the average daily dietary intake of 200 and 300 mg/day; in another study, dental patients used nitinol shape memory alloy instruments for 5 months, and a series of measurement data showed that the concentration of nickel ions in the patient’s blood did not increase significantly. The electrochemical properties and mechanical impregnation tests of the nitinol shape memory alloy bow wire were carried out, and the surface of the bow wire was observed by electron microscopy (SEM) and energy dispersion x-ray detection, and the release of nickel ions was measured by inductively coupled plasma mass spectrometry (ICP-MS), which confirmed that the nitinol shape memory alloy is still lower than the daily dietary intake under certain mechanical pressure and thermal load. Therefore, the nitinol shape memory alloy has demonstrated good biocompatibility in the application of orthopedic stents.
Many scholars use plasma technology to treat the surface of nitinol alloys and conduct comparative experiments with untreated nitinol alloys. During the electrochemical experiments, it was found that the surface corrosion resistance of the surface-treated nitinol alloys was significantly enhanced, and the TiNi coating showed greater roughness and good wettability, thereby increasing cell surface compliance. The MTT results showed that the cell activity and proliferation were similar in the coated, uncoated and negative control groups. However, the early apoptosis rate of the TiNi-coated group was significantly lower than that of the uncoated group, and the cell adhesion, stretching and proliferation of the Tin-coated group were significantly enhanced. In addition, the Tin coating increases the roughness and wettability of nitinol alloy, thereby enhancing the proliferation and adhesion of fibroblasts. A nitinol gradient film was prepared by vapor deposition. Through comparative experiments, it was found that the treated titanium has better hydrophilicity compared with the bare titanium matrix, but there is no significant difference compared with the untreated nitinol, and the untreated nitinol and the treated sample have similar good cell diffusion and adhesion of osteoblasts, so plasma surface treatment has no significant effect on cell activity and adhesion properties. However, the benign interaction between the coated material and the cells is mainly due to the significant improvement in the adsorption efficiency and ability of protein molecules. Therefore, surface plasma treatment makes nitinol alloys have better cell compatibility. Relevant scholars are also continuing to explore the mechanism of action of nitinol alloy surface treatment and cells, proteins, etc., to obtain data support for the continued optimization of the alloy.
Healthy human blood was used to perform hemolysis tests with porous nitinol alloy (NiTi-HA), uncoated porous nitinol alloy (NiTi) and dense pure titanium samples with base apatite coating, respectively. The hemolysis rates of samples in the NiTi group, NITIHA group and Ti group were (0.30±0.11)%, (0.51±0.07)%, (0.27±0.06)%, the hemolysis rate is not higher than 5%, which meets the hemolysis requirements stipulated in the medical material standard, and the porous nitinol alloy after coating exhibits a lower hemolysis rate. The three groups of materials were co-cultured with human SV40 transfected osteoblasts. It was observed that the osteoblasts had grown into the pores of the porous structure, which were irregularly polygonal, with more pseudopods and good stretching. The bone adhesion of each group was in good condition, and the number of cells increased slowly over time. The test results of the alkaline phosphatase (ALP) activity of osteoblasts showed that the ALP activity of the NiTi group and the NiTi-HA group did not differ much and were higher than that of the Ti group. Therefore, porous nitinol alloys and coated porous nitinol alloys can meet the requirements of relevant national medical device standards, and the coated porous nitinol alloys have better biocompatibility.
The auditory bone chain reconstruction material prepared by nitinol shape memory alloy was implanted into the auditory vesicles of guinea pigs, and 5 guinea pigs from the titanium-containing implant group and the blank implant group were randomly sacrificed 7, 14, 28, 56, and 112 days after implantation. Tissue sections were used to perform morphological examination and analysis of tissue cells, staining to observe hair cell apoptosis and deletion, scanning electron microscopy to observe the arrangement of hair cell cilia in the basement membrane of the cochlea, transmission electron microscopy to observe the morphology of hair cell organelles, and auditory sex was performed on guinea pigs in each group before implantation and before execution at different points in time. Brainstem response and distortion response otoacoustic emission detection found that there was no significant change in the tissue morphology of the cochlea of guinea pigs at different points in time. No apoptosis of the hair cells of the cochlea was found. The cilia of the hair cells of the basement membrane cochlea were neatly arranged, and the organelles of the hair cells of the outer ear worm were not significantly abnormal. There was no significant difference in the threshold value of auditory brainstem response for 7, 14, 28, 56, and 112 days before and after implantation in each group, and the pass rate of distortion response to otoacoustic emission was 100%. The results confirmed that nitinol alloy auditory bubble implantation had no significant effect on the morphology and auditory function of the guinea pig cochlea, indicating that the nitinol shape memory alloy has no significant ototoxicity.
Research on the implantation of nitinol shape memory alloy stents into blood vessels in animals has found that they can reduce the chance of formation of attached thrombosis and reduce the risk of acute and non-acute thrombosis occlusion. Therefore, the clinical application of nitinol shape memory alloy vascular stents can reduce the chance of thrombosis, reduce the recurrence rate of patients, and shorten hospitalization and recovery time. It reflects the excellent compatibility of nitinol shape memory alloys in animals.
By implanting nitinol-shaped alloy implants at the far end of the left femur of 51 rats, and heating the alloy implants through electromagnetic induction, the temperature was controlled at 40 to 60℃ to adjust the shape and stiffness of the nitinol-shaped memory alloy implants at the far end of the left femur in rats, blood samples from rats were tested before and after the start of the test, and interleukin-1 (IL-I), IL-4, IL-10, tumor necrosis factor a (TNF-a) and interferon Y (IFN-Y) were measured. After the operation, all groups of human mice recovered well, and there were no obvious adverse reactions. After a week, the animals were put to death for histological examination. There were no significant differences in cytokine measurements and the detection of histological specimens. It has been confirmed that electromagnetic heating and adjusting nickel shape memory alloys have good safety, and it has also been proved that even under reheating conditions, nitinol shape memory alloys still have excellent safety and biocompatibility.
In recent years, with the rapid growth of fracture cases caused by accidental injuries such as traffic accidents and sports injuries, shape memory alloys have attracted more and more attention from doctors clinically. Nitinol shape memory alloy encirclement devices were used to treat 20 cases of multiple rib fractures. X-rays 8 and 12 weeks after surgery showed clinical healing of fractures, no fractures and no healing, loosening of internal fixation, slippage, and alopecia, confirming the good biocompatibility of nitinol shape memory alloys. In addition, a statistical analysis was conducted on the clinical efficacy of treating patella fractures. There were no surgical complications such as deep infection, loosening of internal fixation and fracture after surgery. Both of them had good results, and the nitinol shape memory alloy patella aggregator had the advantages of small trauma, easy operation, and good biocompatibility. It is particularly suitable for comminuted patella fractures.
Retrograde interlocking intramedullary nails combined with nitinol shape memory alloy bone snap rings were used for internal fixation to treat supracondylar femoral type A fractures. 19 patients were treated surgically, and 17 of them were followed up. The clinical healing time of fractures was 12-18 weeks, with an average healing time of 14 weeks. ; There was no loosening of internal fixation, fracture and deformity, joint infection, bone disjunction, etc., 2 cases of superficial incision infection occurred after surgery, 2 cases of knee synovitis, and 1 case of transient exacerbation of the original osteoarthritis. It shows that the biomechanical stability of fracture treatment by this method can effectively restore the stability and integrity of supracondylar femoral fractures, reliable fixation, and promote fracture healing. Moreover, the nitinol shape memory alloy bone snap ring has no loosening, fracture, deformity, and joint infection of internal fixation after implantation, and no fracture delayed healing, showing good tissue compatibility with implants.
With the widespread clinical application of nitinol shape memory alloys, more and more scholars have begun to pay attention to the surface modification of nitinol shape memory alloys to further improve their biocompatibility. The surface of the nitinol shape memory alloy will automatically form a titanium dioxide (Ti02) oxide film, but it is prone to flaking and has limited protective effect on the subsurface surface. Therefore, a single nitinol alloy is not enough to resist adhesion and abrasive wear caused by relative movement. Wear, alloy particles produced by wear can cause sterile loosening of joints after replacement, and ultimately lead to replacement failure. Coupled with the complexity of the human tissue environment, under the erosion of external forces and body fluids, the passivation film on the alloy surface may be peeled off and dissolved. Therefore, nickel ions will be released into the tissues during use, which will cause toxicity, inflammation and other reactions in the organism. The study found that the wear and corrosion of titanium alloys in body fluids occur at the same time, and the corrosion current density increases with the increase of the scratch rate, and corrosion and pitting corrosion are induced by wear and corrosion. In addition, porous nitinol shape memory alloys have a much higher specific surface area than dense alloys due to their porosity, so porous nitinol shape memory alloys are more prone to corrosion in corrosion solutions. In addition, because the nitinol shape memory alloy is directly implanted in the human body and the bone tissue is only a simple mechanical chimeric bond, rather than a strong chemical bone bond, there will be cases where the nitinol shape memory alloy implant is loose and falls off. Therefore, the surface modification of nitinol shape memory alloy to enhance its wear resistance and corrosion resistance, improve its binding force with surrounding tissues, and reduce stress shielding, thereby improving its biological properties has attracted more and more attention from medical workers and researchers. At present, the main surface modification method is to form a coating with high corrosion resistance, wear resistance and good biocompatibility on the surface of nitinol shape memory alloy through various techniques.The main coating technologies are electro-chemical deposition, ion implantation, micro-arc oxidation coating, composite coating and gradient coating. The materials used in the coating are mainly diamond-like (DLO coating, TiN and Tic coating, and other inorganic polymer material coating).
As a traditional process, electrochemical deposition deposits biologically active substances such as proteins and ca/P-containing coatings onto the surface of nitinol shape memory alloys through improved process methods. Electrodeposition is used. The surface of the nitinol shape memory alloy is coated with hydroxyapatite (HA) ceramic by alkali treatment method, and a uniform, dense HA coating is prepared that does not contain other calcium phosphate impurity phases. The histocompatibility of the nitinol shape memory alloy is improved, and it can effectively stimulate the formation of chondrocytes and transform them into bone trabecules, which improves the biological activity of the nitinol shape memory alloy. Ion implantation is a physical alloying process that uses high-energy ion beams to treat the surface of a material to change its surface composition and properties. Ion preparation is used to prepare coating materials with good physical and chemical properties and excellent biocompatible properties. Micro-arc oxidation is a new technology for growing an oxide film in situ on the surface of a material. The oxide film formed by micro-arc oxidation forms many microporous structures due to electrical discharge. This porous structure is conducive to cell adhesion and growth, and implantation into the bone is conducive to the growth of bone tissue. There are still many ways to modify the surface biocompatibility of nitinol shape memory alloys, but there are still many problems, such as the poor binding strength of the coating and the substrate, and the cumbersome preparation process. Therefore, some scholars have used a variety of coating methods to make composite coatings. A composite coating with high binding strength between the coating and the nitinol shape memory alloy has been obtained, which enhances its binding ability to the body’s tissues and cells, reduces the risk of loosening and shedding of nitinol shape memory alloy implants after implantation, and optimizes and improves the biocompatibility of the nitinol shape memory alloy.
Nitinol shape memory alloy has been widely used in the clinical field due to its superior physical and chemical properties. It has excellent biocompatibility and surpasses pure titanium in some aspects. However, the dissolution of nickel in nitinol shape memory alloys has an important impact on their biocompatibility. Therefore, without affecting the excellent mechanics and mechanical properties of the alloy itself, the surface of the nitinol shape memory alloy can be modified to reduce the dissolution of nickel ions in the human environment, and improve the binding strength of tissue cells and nitinol shape memory alloys, improve the stability of implants, and improve their biocompatibility as long-term implants. In recent years, the three-dimensional connective structure of the newly developed porous nitinol shape memory alloy has enhanced the binding strength with bone tissue, but also increased the contact surface area of the alloy with tissue cells, which has also affected its corrosion resistance. Considering that the dissolution of nickel ions due to corrosion has potential toxic effects on the body, the corrosion resistance of nitinol memory alloys provided by surface modification has attracted more and more attention from medical workers.