Magnezyum florür katkılı sığır hidroksiapatit esaslı kompozit biyomalzeme üretim ve karakterizasyonu
Production and characterization of magnesium fluoride doped bovine hydroxyapetite composites
Yazar: NİGAR DEMİR
Danışman: PROF. DR. EYÜP SABRİ KAYALI
İstanbul Teknik Üniversitesi / Fen Bilimleri Enstitüsü / İleri Teknolojiler Ana Bilim Dalı / Malzeme Bilimi ve Mühendisliği Bilim Dalı
Derece: Yüksek Lisans, 2014
Konu: Metalurji Mühendisliği = Metallurgical Engineering

Özet:
Bu çalışmada toz haldeki hidroksiapatit içerisine farklı oranlarda MgF2 takviyesinin ve farklı sinterleme sıcaklıklarının kompozit biyomalzeme üzerindeki fiziksel, mekanik ve biyolojik etkileri incelenmiştir.
Biyomalzemeler, insan vücudundaki canlı dokuların işlevlerini yerine getirmek ya da desteklemek amacı ile kullanılan doğal ya da sentetik malzemeler olup, sürekli olarak veya belli aralıklarla vücut akışkanlarıyla temas ederler. Biyomalzeme olarak kullanılan seramiklerden en popüler olanı Ca10(PO4)6(OH)2 şeklinde gösterilen hidroksiapatittir. Hidroksiapatitin kompozit olarak kullanılmasının amacı sahip olduğu biyouyumluluk ve biyoaktivite özelliklerini kaybetmeden, implant malzemesi olarak kullanımını kısıtlayan zayıf mekanik özelliklerden kurtulmaktır. Hidroksiapatitin içerisine takviye olarak çeşitli malzemeler katılarak mukavemet ve tokluğu yüksek HA bazlı kompozitler elde edilmektedir. Günümüzde HA bazlı biyokompozitler HA-Alümina, HA-zirkonya, HA-biyocam ve HAw (visker) kompozitler vb. oluşmaktadır.
Yapılan bu çalışmada öncelikle hidroksiapatit toz içerisine MgF2 ilave edilerek kompozit toz karışımı hazırlanmıştır. Hazırlanan karışım hidrolik pres yardımıyla silindirik numuneler haline getirilmiştir. Silindirik numuneler 1000, 1100, 1200 ve 1300oC sıcaklıklarda 4 saat bekleme süresi ile sinterlenmiştir. Bu numuneler üzerinden testler gerçekleştirilmiştir.
Mekanik özelliklerden mukavemet ölçümü basma testi ile, sertlik ölçümü Vickers Mikrosertlik yöntemi ile yapılmıştır. Mikroyapı özellikleri Taramalı Elektron Mikroskobu (SEM) ile incelenmiştir. Yapıdaki fazların belirlenmesi için X-ışını kırınımı (XRD) analizleri yapılmıştır. Biyoaktivitenin belirlenmesi için ise numuneler yapay vücut sıvısı SBF içerisinde bekletilerek yüzeyinde oluşan apatit tabakası incelenmiştir.
%1 ve %2 MgF2 katılmış numunelerin hepsinde sinterleme sıcaklığının artmasıyla basma mukavemeti ve mikrosertlik değerlerinin arttığı görülmüştür. Aynı şekilde numunelerin yoğunlukları da sinterleme sıcaklığının artmasıyla artmıştır. Fakat bütün sıcaklıklarda %2 MgF2 içeren kompozitlerin basma mukavemeti, mikrosertlik ve yoğunluk değerleri %1 MgF2 içeren kompozitlerden düşük elde edilmiltir.
En iyi mekanik özellikler %1 MgF2 içeren 1200 ve 1300oC sıcaklıklarda sinterlenmiş  kompozitlerle elde edilmiştir. Bu kompozitlere biyoaktivite testi uygulanmıştır. Bu test sonucunda numunelerin biyoaktif olduğu da görülmüştür. 
Sonuç olarak en iyi mekanik ve fiziksel özelliklere sahip ve biyoaktif olan %1 MgF2 içeren 1200oC sıcaklıklarda sinterlenmiş  kompozit malzeme biyomalzeme olarak kullanılmak üzere önerilebilir.

Abstract:
In this thesis study it was investigated that how are physical, mechanical and biological properties of bovine hydroxyapatite affected by reinforcement of MgF2 powder and by changing the sintering tempertaure.
Ceramic, metallic, polymeric and composite materials are generally used as biomaterials in order to improve human health. In addition to desired mechanical properties of biomaterials, biocompatibility is important in the treatment or replacement of body parts. Prior to the introduction of new biomaterials to the market, detailed biological tests are carried out to prevent any undesired side effects in the body. Both in vitro and in vivo tests are applied initially which is followed by the evaluation with clinical trials of the biological safety and performance.
One of the calcium phosphate compounds with an empiric formula as Ca10(PO4)6(OH)2, hydroxyapatite (HA) is the most widely used bioceramics. It is the most common calcium phosphate ceramics used in the production of implant materials. HA materials have commonly used in bone repairing due to its ability to accelerate the bone growth around the implant. HA is a biocompatible material and used in production of various kinds of prosthesis, repairing the cracked or broken bones and coating of metallic biomaterials.
Hydroxyapatite can be obtained by two ways; synthetic and natural methods. The first synthetic HA biomaterials were synthesized by a chemical precipitation method in 1960s. Afterward, synthetic HA was produced by two different chemical methods. One of them is chemical precipitation from water based solutions containing calcium and phosphate salts, and the other one is the acid-base titration. The synthetic HA is the most commonly used type of HAs and it is highly reliable, however production of synthetic HA is complex and expensive. The production of natural apatite is easier and cheap. Natural HA contains various trace elements that are very important in osseointegration process. The most significant advantage of natural HA used as an implant material is its excellent biocompatibility in the human body. By contrast with synthetic HA, natural HA does not exhibit any toxic effects.
Even though being a biocompatible and bioactive material, hydroxyapatite has a limited usage as an implant material because of its weak mechanical properties. HA material is not suitable for the applications requiring strength such as orthopedics and dentistry. For load bearing applications, metals such as stainless steel, titanium, and cobalt chromium alloys have been widely used. There are, however, various problems related to metallic materials in the human body due to corrosion, wear, and/or negative tissue reaction. 

HA based composites are required to supply improvement of strength and toughness of the implant materials without compromising of biocompatibility. To this end, HA could be used in combination with another metal/ceramic phase, which can improve the physical properties of HA without deteriorating its biocompatibility. The development of improved biocompatible materials with ultimately bone-like mechanical properties is a continuous task in the bioceramics research field.
In this work firstly, freshly cut femurs were deproteinized with 4 N NaOH solution (48 h). After re-irrigation, the samples were subjected to heat treatment at 850˚C for 4 h in open air to securely eliminate any risk of fatal disease transmission. The calcinated BHA bulk pieces were properly ball-milled until fine (<10 m) BHA powder was obtained. 
Afterwards, composite powder mixture prepared by adding 1 % and 2 % MgF2 powder in bovine hydroxyapatite powder. The mixture formed to cylindrical pellets by uni-axially pressing at 350 MPa according to British Standard BS 7253.
Cylincrical samples sintered at the temperatures of 1000, 1100, 1200 and 1300 oC and all samples kept 4 hours at these temperatures. Experimental test applied on these samples.
One of the mechanical tests which was applied to the samples is measuring the strength. Strength was measured by compression test. And also hardness was measured by the Vickers Microhardness method.
Density was measured by Archimedes method.
Microstructures of samples investigated by Scanning Electron Microscopy (SEM). X-ray diffraction analyses done to determine the phases in the structure.
To determine the bioactivity, samples kept in simulated body fluid (SBF) for one, two, three and four weeks. After that samples examined in XRD and SEM. 
After applying physical, mechanical and biological test on samples it was understood that compression strength, microhardness and density are increased by the increasing sintering temperature in all samples.  
The highest values and best properties achieved in the samples which is reinforced by 1% MgF2 and sintered at the temperatures 1200 and 1300 oC. The sample which sintered at the temperature 1200 oC has 94,8 MPa compression strength, 245,335 HV microhardness and 2,661 g/cm3 density. The sample which sintered at the temperature 1300 oC has 95,5 MPa compression strength, 295,5 HV microhardness and 2,7874 g/cm3 density. In vitro tests applied to these samples. 
The composites which have the highest physical and mechanical properties also showed good bioactive properties. The apatite formation was started after two weeks in a simulated body fluid (SBF) for both composites. 


As a result, physical, mechanical and bioactivity tests shows that adding 1% MgF2 to bovine hydroxyapatite and sintering at 1200 oC improves the properties of bovine hydroxyapatite. These materials can be suggested to use as implant material. The biocompatibility tests should be done on these composites to give final decision.