Şekil hafızalı implant malzemelerinin vücut içi uygulamalara yönelik olarak geliştirilmesi
Development of shape memory implant materials for in vivo applications
Yazar: LEVENT ÖNCEL
Danışman: PROF. DR. MAHMUT ERCAN AÇMA
İstanbul Teknik Üniversitesi / Fen Bilimleri Enstitüsü / Metalurji ve Malzeme Mühendisliği Ana Bilim Dalı
Derece: Doktora, 2017
Konu: Metalurji Mühendisliği = Metallurgical Engineering

Özet:
Tedavi yöntemlerinin gelişmesi ve paralelinde medikal implantlardan beklenen fonksiyonların artması neticesinde implant malzemelerinden beklenen performans özellikleri giderek artmakta, geleneksel mühendislik malzemelerinin yetersiz kaldığı durumlar ortaya çıkmaktadır. Şekil hafızalı alaşımlar sahip oldukları süperelastik davranış ve şekil hafızası etkisi gibi özellikler ile geleneksel mühendislik malzemeleri kullanılarak üretilmesi mümkün olmayan implantların üretilmesine imkan sağlamaktadırlar. Günümüzde medikal implant üretiminde en çok kullanılan alaşım nikel-titanyum alaşımı olan nitinoldür. Bu alaşımın vücut içinde kullanıma uygun geçiş sıcaklıklarına sahip olması, biyouyumlu yapısı, korozyon direnci ve mekanik özellikleri medikal implant üretiminde tercih edilen şekil hafızalı alaşım olmasını sağlamaktadır. 
Nitinol malzeme kullanılarak yapılan implant üretiminde en kritik adım ısıl işlem prosesidir. Isıl işlemde kullanılan koşullar çöken fazları, bu fazların miktarını, dağılımını ve çökeltiler arası mesafeyi etkilemektedir. Bu kriterler ise nitinol malzemenin bütün karakteristik özellikleri üzerinde büyük etkiye sahiptir. 
Bu doktora tezi çalışmasında kimyasal kompozisyonu %50,6 nikel, gerisi titanyum olan ve medikal implant sektöründe kullanılan tel halindeki malzemeye uygulanan ısıl işlemde kullanılan şartların, malzemenin hafıza alma davranışına ve mekanik özelliklerine etkileri incelenmiştir. 10 dakika sabit süre ile uygulanan ısıl işlemlerde sıcaklık 540 °C ile 570 °C arasında 10'ar derece artırılmıştır. 550 °C sabit sıcaklıkta uygulanan ısıl işlemlerde ise süre 8 ile 14 dakika arasında değiştirilmiş, süre artırım aralığı 1 dakika olarak seçilmiştir. Isıl işlem deneylerinde elde edilen numuneler optik mikroskop, taramalı elektron mikroskobu (SEM), enerji dağılımlı spektrofotometre (EDS), diferansiyel taramalı kalorimetre (DSC) ve çeşitli mekanik testler ile incelenmiş, ısıl işlem sıcaklık ve süresinin mikroyapı ve mekanik özelliklere etkisi optimize edilmiştir.
Mikroyapı incelemelerinde hafıza alma özelliğinin yapıya NiTi fazı hakim olduğunda ve çok ince boyutlu olmayan Ni4Ti3 çökeltilerinin yapıda düzgün bir dağılım gösterdiğinde meydana geldiği görülmüş ve bu yapının genel olarak 550 °C'de 10 ile 11 dakikalık ısıl işlem sürelerinde elde edildiği tespit edilmiştir. Isıl işlem sıcaklığı ve süresi arttığında ise yapıda bulunan Ni4Ti3 çökeltilerinin boyutlarının incelmesinden dolayı tellerin mukavemetlerinin arttığı ve yorulma özelliğinin kötüleştiği saptanmıştır. İnce taneli Ni4Ti3 fazı içeren bu numunelerde hafıza alma özelliği kaybolmamakla beraber yüksek mukavemetin arzu edilen yorulma özelliğini bozması nedeniyle bu şartlardaki tellerin implant malzemesi olarak kullanımı imkansız hale gelmektedir.
Yapılan bu çalışmalar doğrultusunda hafıza alma kabiliyetine sahip bu tellerden üretilecek implant malzemelerin optimal olarak 550 °C sıcaklıkta 10 veya 11 dakika süre ile ısıl işleme tabi tutulmaları gerektiği ortaya çıkmıştır. Nitekim bu tellerden üretilen medikal implantların uygulanan içeri çekme deneylerindeki davranışları da bu optimal tespiti doğrulamıştır.

Abstract:
Medical implants are devices or tissues that replaces or supports the biological structures inside or on the surface of the body. Implants are used for different purposes in different areas of the body. Properties expected from implant biomaterials vary depending on the purpose of the implant and the place it is going to be implanted. In many medical implant applications, fatigue resistance is a critical point. Hip stems, bone plates and dental implants are the major implants which fatigue resistance has critical importance. Biomaterial's wear resistance is important in many applications including hip and knee implants. MRI compatibility of the biomaterial is an another major point because implant must not move, heat up and cause significant image distortion during magnetic resonance imaging. Biomaterial's corrosion resistance is critical if the implant is in touch with corrosive body fluids. Mechanical properties expected from a biomaterial vary according to the purpose of the implant and the area it will be used. A biomaterial which will be used in coronary stent production and an another biomaterial that will be used in bone plate production will require different mechanical properties. Biomaterials must be biocompatible and must provide required conditions in cytotoxicity, genotoxicity, acute toxicity, irritation, sensitization, hemocompatibility and implantation tests.
There are four types of materials which are used in medical implant production; metals, ceramics, polymers and composites. Between these materials, metals are the most common biomaterials thanks to its electrical conductivity, thermal conductivity and mechanical properties. Iron, chromium, cobalt, nickel, titanium, tantalum, niobium, molybdenum, tungsten and these metal's alloys have been used in medical implant manufacturing. In the past years, stainless steel was the most popular biomaterial because of its mechanical properties, corrosion resistance and biocompatibility. 316 and 316L are the most popular stainless steel grades used in medical industry. When stainless steel is mechanically inadequate or it is aimed to achieve similar strength with using less material, cobalt – chromium alloys have become a suitable alternative and have begun to replace stainless steel. MP35N and L605 are the most commonly used cobalt – chromium alloy grades in medical industry. On the other hand, titanium and its alloys are favored materials in orthopedic implant production.
Due to the development of treatment methods and increase of expectations from medical implants functions, performance features expected from implant materials have increased. There are medical operations that traditional engineering materials like stainless steel, cobalt-chromium and titanium are inadequate. Shape memory alloys offer special features such as superelastic behaviour and shape memory effect and these properties enable production of implants which can't be produced with conventional engineering materials.
There were many studies on various shape memory alloys since superelastic behaviour was discovered in Au-Cd alloy in 1932. In 1938, Greninger and Mooradian reported that they observed formation of thermoelastic martensite in CuZn alloy. In 1951, Chang and Read delivered a comprehensive understanding about superelastic phenomenon mechanism. Later, Reynolds and Bever reported about pseudoelastic effects in CuZn (1952). 4 years later, Hornbogen and Wasserman reported about the same subject. Rachinger published an article about pseudoelastic effects in CuAlNi alloy in 1958. But none of these alloys attracted attention from industry. Breaking moment for shape memory alloys was the discovery of shape memory effect in NiTi alloy in 1963. After technical problems of this alloy was resolved over time, it has got a wide application area. Nitinol is the most commonly used shape memory alloy in medical implant production. Nitinol's suitable transformation temperatures for use in human body, biocompatible structure, corrosion resistance and mechanical properties make it an ideal medical implant material.
Nitinol's critical stress for slip must be high enough to exhibit shape memory effect and superelastic behaviour. In nitinol, critical stress for slip is improved by precipitation hardening. Aging heat treatment is applied to nickel-rich nitinol alloys, which were greater than 50,5at. % Ni, to improve shape memory effect, superelastic behaviour and mechanical properties. Reason of these improvements is formation of Ni4Ti3 precipitates as a result of heat treatment. These coherent precipitates cause stress fields in the microstructure.
Heat treatment process is the most important step of medical implant production when nitinol is used as biomaterial. Heat treatment temperature and heat treatment time affect precipitate type, precipitate volume fraction, precipitate distribution and interparticle distance between precipitates. These criteria about precipitates have strong effect on shape memory effect, superelastic behaviour, transition temperatures and mechanical properties of nitinol.
In this study, effect of heat treatment parameters on shape setting behaviour and mechanical properties of nitinol was investigated. Nitinol material used in experimental studies was in wire form. It's composed of nickel (50,6 at.%) and titanium (balance). In heat treatments with constant time (10 minutes), temperature was increased from 540 °C to 570 °C at 10 °C intervals. In heat treatments with constant temperature (550 °C), time was increased from 8 minutes to 14 minutes at 1 minute intervals. Heat treated samples were characterized by optical microscope, scanning electron microscope (SEM), energy dispersive spectrometer (EDS), differential scanning calorimeter (DSC) and various mechanical tests. Effect of heat treatment temperature and heat treatment time on microstructure and mechanical properties of nitinol was optimized.
In microstructural examinations, it is determined that shape setting results are stable when NiTi phase is dominant and Ni4Ti3 precipitates over a certain size spread uniformly throughout the microstructure. This microstructure was obtained at heat treatment times of 10 and 11 minutes at 550 °C heat treatment temperature. When heat treatment temperature and heat treatment time were increased, strength of nitinol wires were increased and fatigue resistance was decreased as a result of smaller Ni4Ti3 precipitate formation. Shape setting results are still stable in samples with fine Ni4Ti3 precipitates but decrease in fatigue life make these wires unusable as an implant material.
This study shows that medical implants which consist of nitinol wires should be heat treated for 10 or 11 minutes at 550 °C. Also, behaviour of medical implants, which were produced from these nitinol wires, in the retraction force test verified that optimal finding.