UNIVERZITET U BEOGRADU TEHNOLOŠKO-METALURŠKI FAKULTET Nenad L. Ignjatović SINTEZA I DIZAJNIRANJE STRUKTURE I OSOBINA HIDROKSIAPATIT/POLILAKTID KOMPOZITNIH BIOMATERIJALA doktorska disertacija Beograd, 2001 UNIVERSITY OF BELGRADE FACULTY OF TECHNOLOGY AND METALLURGY Nenad L. Ignjatović SYNTHESIS AND DESIGNING OF THE STRUCTURE AND PROPERTIES OF COMPOSITE BIOMATERIALS HYDROXYAPATITE-POLYLACTIDES Doctoral Dissertation Belgrade, 2001 Apstrakt Koštani defekti mogu se reparisati biomaterijalima na bazi sintetskog hidroksiapatita (HAp). U slučaju reparacije koštanih defekata sa prekidom kontinuiteta, neophodno je da upotrebljeni biomaterijal zadovolji biomehaničke uslove. Poboljšanje mehaničkih osobina HAp- a ostvareno je njegovim ojačavanjem biokompatibilnim pofimerima. Predmet ovih istraživanja je sinteza i dizajniranje strukture i osobina kompozitnih biomaterijala hidroksiapatit-polilaktida. Upotrebom bioresorbilnog poli-l-laktida (PLLA) i bioneresorbilnog HAp-a dobijen je kompozitni biomaterijal HAp/PLLA sa mehaničkim osobinama bliskim prirodnom koštanom tkivu. Mešanjem potpuno rastvorenog PLLA sa komponentom HAp-a, a zatim vakuum uparavanjem, dobijen je visoko porozni kompozit. Ova vrsta kompozita je naknadno dizajnirana hladnim i toplim presovanjem. U ovim istraživanjima ispitan je uticaj presovanja na degradacione promene tokom kompaktiranja, molsku masu PLLA i kompresionu čvrstoću. Definisan je uticaj parametara presovanja, kao što su temperatura, pritisak i vreme na poroznost, kompresionu čvrstoću i modul elastičnosti. Ispitan je uticaj veličina čestica HAp-a i molske mase PLLA na analizirane osobine. Mogućnosti primene kompozitnog biomaterijala HAp/PLLA u realnim, in vivo uslovima ispitane su primenom FT-IR spektroskopije. Tokom procesa primene dolazi do formiranja novog vezivnog tkiva kolagena, uz stvaranje novih kolagenskih grupa koje su registrovane FT-IR spektroskopijom. Implanti od HAp/PLLA kompozita intraperitonealno su implantirani. a nakon 2, 7 i 12 nedelja od impfantacije histopatološki analizirani. Mogućnosti zamene, do sada široko korišćene, primene autologne kosti u reparacijama koštanog tkiva, takođe je analizirana u ovoj doktorskoj disertaciji. Ključne reči: hidroksiapatit-polilaktid, kompozitni biomaterijal, sinteza, osobine, toplo presovanje, poroznost, kompresiona čvrstoća, modul elastičnosti, in vitro, in vivo test Abstract Bone-defects can be repaired using biomaterials based on synthetic calcium- hydroxyapatite (HAp). The bone tissue repair, in the case of broken bone continuity, can successfully be made by a biomaterial of corresponding mechanical properties. Adequate mechanical properties of biocomposite blocks can be reached by reinforcing HAp with biocompatible polymers. The research subject of this study are the synthesis and designing of the structure and properties of composite biomaterials hydroxyapatite-polylactides Using biocompatible and bioresorptive poly-L-lactide (PLLA) polymer, HAp/PLLA composite biomaterial consisting of a non-bioresorptive HAp and bioresorptive PLLA component with mechanical properties similar to those of bones can be produced. Completely dissolved PLLA with HAp granules gives a mixture, from which, after evaporation in vacuum, HAp/PLLA composite biomaterial of high porosity is formed. The material obtained in this way can be compacted by hot and cold pressing. In order to investigate the influence of hot pressing time on the degradation changes, the molecular weight of PLLA and compressive strength of biocomposite before and after hot pressing have been analyzed. The effects of hot pressing parameters such as temperature, pressure and time, on the porosity, compressive strength, elasticity modulus and the mechanism of fracture formation of hot pressed blocks have been investigated, as well as their dependence on the HAp particle sizes and PLLA molecular weights. In this research the bone tissue repair process in vivo using HAp/PLLA composite biomaterial was studied by FT-IR spectroscopy. Implants made of HAp/PLLA biocomposites with PLLA were studied 2, 7 and 12 weeks after being implanted intraperitoneally. Also, a possible substitution of the autologous bone with HAp/PLLA biocomposites, in filling up bone defects, was investigated. Keywords: hydroxyapatite-polylactide, composite biomaterials, synthesis, properties, hot pressing, porosity, compressive strength, modulus, in vitro, in vivo tests Naučna oblast: hemijska tehnologija Uža naučna oblast: nauka o materijalima Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org) Powered by TCPDF (www.tcpdf.org)