Synthesis and designing of the structure and properties of composite biomaterials hydroxyapatite-polylactides

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 HApa 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.Bone-defects can be repaired using biomaterials based on synthetic calciumhydroxyapatite (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

Preparation of composite material BCP/DLPLG with a different content of ceramic and polymer component

Using a new approach of synthesis, homogenisation of DLPLG polymer powder and BCP gel, BCP/DLPLG composite material has been obtained with morphological and structural characteristics making it potentially very suitable for practical application in certain fields of the reconstructive medicine. The composite material has been synthesised with different ratios of ceramics and polymer BCP/DLPLG; 65/35w/w, 10/90 w/w, 5/95 w/w and 2/98w/w. The samples were characterized by Differential Scanning Calorimetry (DSC) and Scanning Electron Microscopy (SEM).Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Application of hydroxyapatite granules in mastoid obliteration

The primary goal of surgical intervention for chronic middle ear disease is to development of a safe, dry, and low-maintenance ear. Persistent moisture, infection, and drainage is problematic in about one-third of patients, but also requiring revision surgery as canal-wall-down mastoidectomy. Despite best practice and continuous care, an open mastoid cavity is a handicap for the patients. The patients usually requires regular cleaning and life-long protection of the ear against water. During life, it could be a source of ear discharge due to irritation mucosal lining. The principle of mastoid obliteration was introduce as early as 1911. Over the years different biological tissues have been used to obliterate mastoid cavities including fat tissue, cartilage, musculo-periostal flap and autogenous bone. However, these tissue all suffer from atrophy or resorption with time. While all the intial reports were on the use of biological tissues, there has been an increasing interest in synthetic materials.Hydrxyaopatite is a well-known biocompatible ceramic with a long history of success in middle ear surgery. Experimental studies have demonstrated that hydroxyapate granulae do not undergo morphological changes after long term inplanatation in the temporal bulae. The purpose of our work is to present an importance of hydroxyapatite granule for mastoid obliteration of open radical mastoid cavities and to point out a new concept as application of nanocrystalline calcium phosphate in otosurgery. In our retrospective review, we found that the majority of individuals undergoing mastoid surgery with obliteration achieved a dry ear and there was a reduction of clinic visits during fellow-up period between 1 to 5 years

Application of hydroxyapatite granules in mastoid obliteration

The primary goal of surgical intervention for chronic middle ear disease is to development of a safe, dry, and low-maintenance ear. Persistent moisture, infection, and drainage is problematic in about one-third of patients, but also requiring revision surgery as canal-wall-down mastoidectomy. Despite best practice and continuous care, an open mastoid cavity is a handicap for the patients. The patients usually requires regular cleaning and life-long protection of the ear against water. During life, it could be a source of ear discharge due to irritation mucosal lining. The principle of mastoid obliteration was introduce as early as 1911. Over the years different biological tissues have been used to obliterate mastoid cavities including fat tissue, cartilage, musculo-periostal flap and autogenous bone. However, these tissue all suffer from atrophy or resorption with time. While all the intial reports were on the use of biological tissues, there has been an increasing interest in synthetic materials.Hydrxyaopatite is a well-known biocompatible ceramic with a long history of success in middle ear surgery. Experimental studies have demonstrated that hydroxyapate granulae do not undergo morphological changes after long term inplanatation in the temporal bulae. The purpose of our work is to present an importance of hydroxyapatite granule for mastoid obliteration of open radical mastoid cavities and to point out a new concept as application of nanocrystalline calcium phosphate in otosurgery. In our retrospective review, we found that the majority of individuals undergoing mastoid surgery with obliteration achieved a dry ear and there was a reduction of clinic visits during fellow-up period between 1 to 5 years

Synthesis of BCP and BCP/PLGA biomaterials by ultrasonic spray pyrolysis

The most significant mass part of the bony tissue consists of calcium phosphate ceramics. This paper describes method of obtaining fine particles of biphasic calcium phosphate (BCP) as well as fine particles of biphasic calcium phosphate covered by polymer, poly-lactide-co-glycolide (BCP/PLGA), by ultrasonic spray pyrolysis. Methods used for characterization of obtained particles of BCP and BCP/PLGA are Infrared Spectroscopy (IR) and Scanning Electron Microscopy (SEM) techniques.Physical chemistry 2004 : 7th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 21-23 September 200

Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol

Cholecalciferol, vitamin D3, plays an important role in bone metabolism by regulating extracellular levels of calcium. Presented here is a study on the effects of the local delivery of cholecalciferol (D3) using nanoparticulate carriers composed of hydroxyapatite (HAp) and poly(D,L-lactide-co-glycolide) (PLGA). Multifunctional nanoparticulate HAp-based powders were prepared for the purpose of: (a) either fast or sustained, local delivery of cholecalciferol, and (b) the secondary, osteoconductive and defect-filling effect of the carrier itself. Two types of HAp-based powders with particles of narrowly dispersed sizes in the nano range were prepared and tested in this study: HAp nanoparticles as direct cholecalciferol delivery agents and HAp nanoparticles coated with cholecalciferol-loaded poly(D,L)-lactide-co-glycolide (HAp/D3/PLGA).Satisfying biocompatibility of particulate systems, when incubated in contact with MC3T3-E1 osteoblastic cells in vitro, was observed for HAp/D3/PLGA and pure HAp. In contrast, an extensively fast release of cholecalciferol from the system comprising HAp nanoparticles coated with cholecalciferol (HAp/D3) triggered necrosis of the osteoblastic cells in vitro. Artificial defects induced in the osteoporotic bone of the rat mandible were successfully reconstructed following implantation of cholecalciferol-coated HAp nanoparticles as well as those comprising HAp nanoparticles coated with cholecalciferol-loaded PLGA (HAp/D3/PLGA). The greatest levels of enhanced angiogenesis, vascularization, osteogenesis and bone structure differentiation were achieved upon the implementation of HAp/D3/PLGA systems.This is the peer-reviewed version of the articleIgnjatović, N., Uskoković, V., Ajduković, Z., Uskoković, D., 2013. Multifunctional hydroxyapatite and poly(d,l-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol. Materials Science and Engineering: C 33, 943–950. [https://doi.org/10.1016/j.msec.2012.11.026]Published version: [https://vinar.vin.bg.ac.rs/handle/123456789/7411

Multifunctional nano scale drug delivery particles based on vitamin D3-loaded hydroxyapatite in bone tissue engineering

Specific group of controlled drug delivery systems in bone tissue engineering are multifunctional nanoparticle systems (MNPs) based on hydroxyapatite coated with drug loadedbioresorbable polymer. This study illustrates the possibility for controlled synthesis of multifunctional nanoparticulate forms based on hydroxyapatite as a system for local delivery of vitamin D3 and secondary delivery of defect filler hydroxyapatite. The results were two type of nanoparticle powder of controlled shapes, sizes and properties: hydroxyapatite nano particles as vitamin D3 carriers (HAp/D3) and vitamin D3-loaded hydroxyapatite coated with poly-D,Llactide-co-glycolide (HAp/D3/PLGA) with particle sizes of d50=68 nm and d50=71 nm, respectively. Simultaneously, biocompatibility of the materials was tested in vitro, on osteoblastic MC3T3-E1 and epithelial Caco-2 cells in culture. Biocompatibility tests carried out on cell cultures have shown intact monolayers of epithelial cells in contact with both materials and no negative effects on the cell viability. The aim of this work was application in living/human systems, and it has been tested in vivo; artificially made bone defects of a mandible damaged by osteoporosis have been reconstructed with both types of materials. The best results were achieved 24 weeks after implantation of vitamin D3-loaded hydroxyapatite coated with poly-D,L-lactide-co-glycolide. Accelerated angiogenesis, vascularization, osteogenesis and bone structure differentiation has been achieved in the presence of specific islet-like forms of ossification centers

Scanning electron microscopy study of changes in nanoparticles surface under in vitro simulated physiological conditions

In this study we observed the changes in surface of nanoparticles of two different nanomaterials, cobalt-substituted hydroxyapatite (CoHAp) and calcium phosphate/poly-(DLlactide-co-glycolide) (CP/PLGA) that occurred under simulated physiological conditions in vitro. Both nanomaterials were incubated in an appropriate volume of Dulbecco's Modified Eagle Medium (DMEM) for 3 days at 37 0C and then the medium was removed and materials were dried. Surface changes of nanoparticles were studied by scanning electron microscopy (SEM). Results of SEM analysis show that changes in the size and shape of the nanoparticles took place. These changes can be explained by interactions of nanomaterials with DMEM. In the case of CP/PLGA it was probably the result of polymer degradation and changes in CoHAp nanoparticles were probably the result of ion exchange

Structure and characteristics of the hot pressed hydroxyapatite/poly-L-lactide composite

Hydroxyapatite/poly-L-lactide (HAp/PLL) composite biomaterial can be obtained by different processing methods. Three-dimensional blocks of HAp/PLLA composite biomaterial with mechanical characteristics close to the natural bone tissue can be obtained by hot pressing procedure. Effects of synthesis and compacting on the structure and characteristics of the HAp/PLLA composite biomaterial were studied in this work. Using wade angle X-ray structural analyses (WAXS), differentially scanning calorimetry (DSC), thermogravimetric analysis (TGA) and infrared (IR) spectroscopy, the changes occurring in the material during synthesis and hot pressing were monitored. Surface microstructure was analyzed by scanning electronic microscopy (SEM) coupled with electron-dispersion analysis (EDX). The results obtained indicate a possible decrease in the degree of crystallinity with hot pressing time increase. A block of HAp/PLLA composite biomaterial with 1.6 times lower crystallinity of the polymer phase was obtained by hot pressing in a given time interval with a maximum of 60 minutes. Results of TG analysis show that PLLA stability decreases with increasing hot pressing time, and vice versa. IR study proved that neither destructive changes in constituents nor formation of new phases occurred during hot pressing

Scanning electron microscopy study of changes in nanoparticles surface under in vitro simulated physiological conditions

In this study we observed the changes in surface of nanoparticles of two different nanomaterials, cobalt-substituted hydroxyapatite (CoHAp) and calcium phosphate/poly-(DLlactide-co-glycolide) (CP/PLGA) that occurred under simulated physiological conditions in vitro. Both nanomaterials were incubated in an appropriate volume of Dulbecco's Modified Eagle Medium (DMEM) for 3 days at 37 0C and then the medium was removed and materials were dried. Surface changes of nanoparticles were studied by scanning electron microscopy (SEM). Results of SEM analysis show that changes in the size and shape of the nanoparticles took place. These changes can be explained by interactions of nanomaterials with DMEM. In the case of CP/PLGA it was probably the result of polymer degradation and changes in CoHAp nanoparticles were probably the result of ion exchange