Papers by Author: Besim Ben-Nissan

Abstract: The new novel implant designs include the functionality of advanced drug delivery systems in order to improve osteointegration and to inhibit the implant-related post-operative infections. In this research, Ti6Al4V metallic implants were coated with the multifunctional-dual slow drug delivery coating which includes a polymeric matrix system based on a poly-lactic acid thin film and a bioactive ceramic hydroxyapatite. This system consists of two different kinds of pharmaceuticals, which are gentamicin and simvastatin. It is reported in this paper that the simvastatin and gentamicin containing poly-lactic acid coating which was applied uniformly and successfully with and without hydroxyapatite microspheres. Most importantly, the release rate of drugs was controlled with PLA matrix and HAp microspheres which have different dissolution rates in order to prevent the high dosages causing adverse side-effects of drugs.

Abstract: Surface modifications have been progressively applied in order to improve the mechanical, biological and chemical properties of metallic dental and orthopedic implants. Therefore, the novel and multifunctional biocomposites coating matrices, which also consist of local and targeted drug delivery systems, are the most recent applications in the medical field. In this study, gentamicin antibiotic containing HAp bioceramics were utilized in a biodegradable poly-lactic acid thin film matrix which was applied to Ti6Al4V metallic implant surfaces. nanoindentation and scratch test methods were applied. It was observed that, bonding between coating and the substrate is strong enough to be used in implant applications. Additionally, it was observed that the hardness and young modulus values of uncoated Ti6Al4V disc which were 4.3 and 125.2 GPa, respectively. However, under the same testing conditions, it was also observed that the H values (0.6-0.8GPa) and the E (50-60 GPa) values of PLA-HAp biocomposite coated samples are slightly higher than the H values (0.4-0.6 GPa) and the E values (40-50GPa) of only PLA coated sample.

Abstract: Nowadays hydroxyapatite (HA) bioceramics are very important because increasing traffic accidents and ageing of the population. They can be produced from synthetic or natural sources with different production methods. The biggest negative issue of HA is being very brittle and unstable under pressure. Various materials are added for restoring these weaknesses, but there is not so much studies adding nano-ingredients for restoring the mechanical properties of HA. In this study, 5-10% nano-yittria-oxide is added to bovine derived HA (BHA) and to commercial synthetic (CSHA) as a control group. Physical and mechanical properties are examined. Results show that adding of nano-ingredients are really helping to mechanical properties of HA.

Abstract: Marine structure, coralline materials were converted to calcium phosphate using two different phosphate solutions. The aim was to study the conversion mechanisms under acidic and basic environment at moderate conditions of temperature. Crystal growth and morphology of converted corals were characterized by XRD and SEM respectively. The results suggested that under acidic conditions (H₃PO₄), dissolution and precipitation control and direct the crystal formation and morphology in which transition from plate like to rod like hydroxyapatite structure was favoured. Metastable phase such as monetite formed and transformed to HAp during reaction. During the first hour of the dissolution a monetite and hydroxyapatite mixture precipitates and then the full conversion to hydroxyapatite is observed. On the other hand, under basic conditions (NH₄)₂HPO₄, just diffusional surface conversion of the calcium carbonate structure of coralline materials to hydroxyapatite and a very small amount of tri-calcium phosphate is observed. The mechanism can be classified as the solid-state topotactic ion-exchange reaction mechanism.

Abstract: Drug delivery systems were developed from coralline hydroxyapatite (HAp) and biodegradable polylactic acid (PLA). Gentamicin (GM) was loaded in either directly to PLA (PLAGM) or in HAp microspheres. Drug loaded HAp was used to make thin film composites (PLAHApGM). Dissolution studies were carried out in phosphate buffered saline (PBS. The release profiles suggested that HAp particles improved drug stabilization and availability as well control the release rate. The release also displays a steady state release. In vitro studies in human Adipose Derived Stem Cells (hADSCs) showed substantial quantities of cells adhering to hydroxyapatite containing composites. The results suggested that the systems could be tailored to release different clinical active substances for a wide range of biomedical applications.

Abstract: Calcium phosphates are very important biomaterials for orthopaedic and dental applications. Hydroxyapatite (HA) is one of the important phases used for grafting. Those are produced from synthetic and natural sources with various methods. Especially nano-bioceramics can be produced through calcitic and aragonitic structures (i.e. mussel shells, sea snail shells, land snail shells and sea urchin shells). The plate limpet shells were used. The plate limpet is a gastropod, a soft-bodied invertebrate (an animal without a backbone) that is protected by a very hard, flattened conical shell. In this study the Plate Limpet (Tectura scutum) shells were obtained from a local gift store in Istanbul. The habitation of these limpets broadens from south Alaska down to California - Mexico. First the exact CaCO₃ content was measured with thermal analysis (DTA/TGA). Here in this study agitation was carried out on a hot-plate (i.e. mechano-chemical processing). First the temperature was set at 80 °C for 15 min. Then equivalent amount to CaO H₃PO₄ was added dropwise for HA phase formation and the reaction was set on a hotplate for 8 hours. The dried sediments HA part was divided into 2 groups. One group was sintered to 835 °C and second group to 855 °C. Here x-ray diffraction and scanning electron microscope (SEM) studies were performed. From the study various HA phases and TCP phases were obtained. A previous study done with Atlantic Deer Cowrie encourages nanobioceramic production from natural sources. This study proposes that mechanochemical agitation with very simple way for producing nano-sized calcium phosphates for future bioengineering scaffold applications.

Abstract: Bioceramics is very important application for dental and orthopedic procedures. Beside all these normal procedures traffic accidents are requiring increasing number of graft, prostheses and orthosis applications. Bioceramics can be produced from local and natural sources with various methods. Those can be produced from various bone structures through calcination (at high temperatures) or with diluted hydrochloric acid (HCl) application & freeze drying. Beside these methods calcite and aragonite structures like from sea shells and egg shells bioceramic production can be realized through mechanochemical processing via a simple hot-plate or ultrasonic equipment. A fresh water snail shell (Zebra Nerite Snail - Neritina natalensis) was prepared as bioceramic production source. The resulting hydroxyapatite (HA) powders were obtained without any impurities. At two varying temperature of 865 and 885 °C the snail shells was transformed to HA bioceramics. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential thermal analysis (TG/DTA) were evaluated.

Abstract: The process is a simple chemical method and aims to produce nano-structured calcium phosphate powders from natural sources, for biomedical applications. For this purpose, Atlantic Deer Cowrie (ADC) shells (Cypraea cervus Linnaeus, 1771) were collected from a local gift store in Istanbul. The empty shells were cleaned and crushed then were ball milled and sieved under 100µm. The raw powders were suspended on a hotplate stirrer for a simple chemical agitation. The temperature was kept at 80°C for 15 min. and then appropriate amount of H₃PO₄ was added by titration into the prepared solution to form calcium phosphate precursors. The solution was stirred on a hotplate for 8 hours then dried at 100°C for 24 hours. Afterwards the resulting dried sediments were collected and heat treated between 400-800°C for 4 hours, dependent on the required specific calcium phosphate phase. X-ray diffraction (XRD) analysis and scanning electron microscopy (SEM) were carried out for identifying various hydroxyapatite (HA), tricalcium phosphate (TCP) and other calcium phosphate phases. Various particle sizes ranging from nano to micron, are obtained depending on the chemistry used and the processing technique applied during the production. A range of calcium phosphate phases can be obtained from ADC shells, by using a simple and economic conversion method. Proper cleaning methods developed and appropriate preparation techniques will enable us to use these nano calcium phosphate powders in orthopedic and dental applications.

Abstract: Simvastatin has been shown to succesfully stimulate bone regeneration and attention has being focussed on developing appropriate delivery carriers for its release. The challenge of deliverying therapeutic concentration of pharmaceutical compunds has being the centre of focus in drug delivery developments. This study examines the in-vivo effects of simvastatin released from β-TCP macrospheres derived from coral exoxskeletons. The results indicates that the controlled release of simvastatin can promote bone formation comparable with direct injection. Furthermore the results showed that the release of simvastatin delivery rates can be controlled by additional coating of an apatite coating. Analysis by CT scans, SEM, amount of new bone formed and mechanical strength tests, showed that by controlling the release of simvastatin bone formation can be stimulated to a therapeutic level.

Abstract: The production of nano-calcium phosphate powders, such as HA (hydroxyapatite), from synthetic chemicals can be expensive and time consuming. The skeleton or shells of sea creatures (e.g. sea urchins, shells, corals) could be an alternative source of materials to produce very fine and even nano-structured calcium phosphate biomaterial powders. Ηydrothermal conversion under very high pressures or methods such as hot-plating (chemical) or ultrasonication (mechano-chemical), have been proposed to transform naturally derived CaCO₃, e.g. aragonite, into apatite based materials. The aim of the present work was to prepare inexpensive nano-sized HA and TCP bioceramics powders from a local sea snail shells as a possible raw material for HA/TCP bioceramics. Empty shells of a local sea snail (Nassarius hinia reticulatus) from Marmara Sea, Turkey were collected from a beach near Istanbul. The collected shells were ground to a particle size <75µm. Thermal analyses (DTA/TGA) were performed to determine the exact CaCO₃ content and thermal behavior. The raw powder was suspended in an aqueous media which was placed in an ultrasonic bath. The temperature was set at 80°C for 15min. Then, an equivalent (to CaO content) amount of H₃PO₄ was added drop by drop very gently into the solution. The reaction continued for 8h, following which the liquid component was evaporated off in an incubator at 100°C for 24h. The dried sediment was collected and heat treated at two different temperatures, 400 and 800°C. The morphology of the powders produced was examined using SEM. The crystalline phases were indentified using X-ray analysis. X-ray diffractograms indicated the presence of two calcium phosphate phases, namely HA and whitlockite. SEM observations showed that the powder produced comprised nano-sized particles. FTIR results also indicated the presence of HA and whitlockite structures. The experimental results suggest that Nassarius hinia reticulatus shells could be an alternative source for the production of various mono or biphasic calcium phosphates. In this study, local sea snail shells were successfully converted to HA and whitlockite with a simple mechano-chemical (ultrasonic) conversion method without the use of complex hydrothermal methods.