From Micro to Nano Biphasic Calciumphosphate/Poly-Dl-Lactide-Co- Glycolide Composite Biomaterials for Hard Tissue Reconstruction

Poster presented at the Pittcon 2007 - Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, February 25 – March 2, 2007

Molecular spectroscopy analysis of the substitution of bone tissue by HAp/PLLA composite biomaterial

Due to its pronounced osteoinductive properties, calcium hydroxyapatite (HAp) has been widely used in medicine. Bioresorptive poly-L-lactide (PLLA) as a polymer biomaterial has been also used extensively in medicine for its non-toxicity and biocompatibility. To combine the advantages exhibited by each of these materials, a HAp/PLLA composite biomaterial has been synthesized and used for reconstruction and repair of bone defects. Hydroxyapatite/poly-L-lactide (HAp/PLLA) composite biomaterial with PLLA of 50,000 and 430,000 g/mole molecular weight was studied in vivo. The biocomposite with PLLA of both molecular weights was implanted into mice, then removed from their organisms and analyzed by the Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and histopathologic analysis. Characteristic absorption bands, registered and defined by FT-IR spectroscopy, confirm the formation of new functional groups and compounds during the bone repair process using HAp/PLLA biocomposite with PLLA of 50,000 and 430,000 molecular weights. Analysis of the microstructures of the sample surfaces by scanning electron microscopy (SEM) before and after implantation revealed bioresorption of the PLLA polymer phase in the system with PLLA of lower molecular weight and generation of collagen fibers at the sites of implanted bioresorptive PLLA. As the studied synthetic materials behave as the natural bone, i.e., they are phagocytosed and resorpable, they can be considered as biocompatible

Synthesis and Characterization of Hydroxyapatite-Collagen Biocomposite Materials

Hydroxyapatite-collagen composite is a prosperous biomaterial in reconstructive surgery for the reparation of defects within human hard tissue. Within this research, three-dimensional blocks of HAp/collagen composite biomaterial were synthesized by homogenizing the HAp/collagen mixture by cold and hot (T=60oC) pressing (P=49 MPa). The changes in the system were followed by using thermal analysis (DSC & TGA), FT-IR spectroscopy and scanning electron microscopy (SEM). The identification and kinetic analysis of appearing phase transition were done. FT-IR spectrum of the biocomposite shows that neither cold nor hot pressing had significant influence on the individual components of the composite. SEM of the fracture surfaces showed that more intimate contact between the phases happened during hot consolidation. The obtained results suggest that the native structure of collagen molecules was destroyed, but the primary structure was maintained. Such a mild modification of collagen molecules can possibly lead to elimination of antigenicity effects after implantation of this kind of biomaterial into human body

One-shot Nano-device for Treatment of Peri-implantitis: Biological Proof of Concept

Objectives To compare biological effects of experimental nano device composed of nano-hydroxyapatite loaded with clindamycin, embedded in PLGA for continual release of daily MIC against Porphiromonas gingivalis for 21 days bone healing period (CLHap) with effects of nano-hydroxyapatite (Hap) and commercial bone substituent (BioOssÒ). Methods 6 female beagle dogs with similar characteristics underwent teeth extractions, implant placement and ligature induced PI, and were further surgically treated. Following open-flap debridement, the biomaterials were randomly allocated to ensure the serial distribution of antimicrobial material for pharmacokinetic testing of antibiotic systemic release. The biochemical and microbiological markers were compared before disease induction (baseline), before the treatment (pre-op) and 3 months (3m) following treatment. GM-CSF, TNFa, IL-6, IL-10 and OPG concentrations were estimated using Luminex method, while the RT-PCR kit was developed for quantification of the Porphyromonas gulae. Finally, following animal sacrifice, specimens were retrieved for histological analyses. Following fracture technique, decalcified samples were sectioned and stained for histomorphometric assessment of: apical extension of barrier epithelium (aBE), infiltrated connective tissue (ICT) area and respective apical extension (aICT). Results The pharmacokinetic test confirmed safety of the experimental material according to undetectable blood concentrations of the antibiotic. The concentrations of P. Gulae, GM-CSF, TNFa, OPG, IL-6 and IL-10 significantly decreased following treatment only in CLHap group while in other groups the changes remained insignificant. Both ICT and aICT were significantly lower CLHap when compared to both control groups. Conclusions Results of the present study demonstrated safe and promising treatment capacity of the experimental CLHap for managment of peri-implantitis

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

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

Germanium-doped hydroxyapatite: Synthesis and characterization of a new substituted apatite

Hydroxyapatite (HAp) is the major component of all boney tissues in mammals. Because of this omnipresence in the living world, HAp possesses an exceptional biocompatibility. The downside of this omnipresence, however, comes in the form of its mild to moderate biological activities. One means of augmenting these activities involves the doping of HAp with foreign ions. Here, the first synthesis and characterization of HAp doped with germanium ions is being reported. Germanium was deliberately integrated into the crystal lattice of HAp in the form of germanate anions. Approximately two thirds of the germanate ions introduced into the hydrothermal solution got incorporated into the HAp lattice, yielding the approximate stoichiometry of Ca10-x(PO4)5.62+y(GeO3)0.38(OH)2-z. Germanates replaced the phosphates of stoichiometric HAp and induced the expansion of the HAp lattice both along the screw axis of the calcium ion hexagons and in the direction parallel to the basal plane. Simultaneously, the larger size and the triple valency of the germanate ion as compared to the smaller and trivalent phosphates prompted the bond distortion and charge compensation through defect formation, which reduced the crystallinity and increased the microstrain of the HAp lattice. Vibrational spectroscopic analyses corroborated these crystallographic effects by demonstrating the enhanced heterogeneity of the environments surrounding the active modes after germanate ions were incorporated into HAp. Conforming to La Châtelier's principle, this reduction of the crystallographic order increased the capacity of the material for integration of adventitious carbonates. However, the inclusion of germanate ions induced a partial shift of these carbonates to the hydroxyl channel sites, thus decreasing the ratio of the B-type carbonation to the A-type carbonation. Introduced into HAp, germanium acted as a superb regulator of the particle size and morphology, enhancing their fineness and uniformity. Inclusion of germanate ions also increased the electrophoretic mobility and hydrodynamic surface charge density of the particles by reducing their size and by inducing a more stochastic distribution of terminal ionic groups due to the bending of the crystal facets. Overall, the doping of HAp with germanate ions facilitated the production of narrowly dispersed nanorods with a moderately enhanced structural disorder and with a pronounced potential for the biomedical niche. © 2022 The Author(s

Sonochemical Preparation of Hydroxyapatite/Poly (lactide-co-glycolyde) Composite

Poster presented at the 9th Conference of the Yugoslav Materials Research Society - YUCOMAT 2007, Herceg Novi, Crna Gora, September 10-14, 2007

Preparation and Characterization of Poly-l-lactide Microspheres

Poster presented at the International Workshop and Summer School Cell and Tissue Engineering, Faculty of Technology and Metallurgy, University of Belgrade, July 1-8, 2006

Precipitation Synthesis and Two-Step Sintering of Hydroxyapatite Nanopowders

Poster presented at the 11th Conference of the Materials Research Society of Serbia - YUCOMAT 2009, Herceg Novi, Montenegro, August 31 – September 4, 2009