Zilgma Irbe

Calcium phosphate bone cements for local vancomycin delivery

Among calcium phosphate biomaterials, calcium phosphate bone cements (CPCs) have attracted increased attention because of their ability of self-setting in vivo and injectability, opening the new opportunities for minimally invasive surgical procedures. However, any surgical procedure carries potential inflammation and bone infection risks, which could be prevented combining CPC with anti-inflammatory drugs, thus overcoming the disadvantages of systemic antibiotic therapy and controlling the initial burst and total release of active ingredient. Within the current study α-tricalcium phosphate based CPCs were prepared and it was found that decreasing the solid to liquid phase ratio from 1.89g/ml to 1.23g/ml, initial burst release of vancomycin within the first 24h increased from 40.0±2.1% up to 57.8±1.2% and intrinsic properties of CPC were changed. CPC modification with vancomycin loaded poly(lactic acid) (PLA) microcapsules decreased the initial burst release of drug down to 7.7±0.6%, while only 30.4±1.3% of drug was transferred into the dissolution medium within 43days, compared to pure vancomycin loaded CPC, where 100% drug release was observed already after 12days. During the current research a new approach was found in order to increase the drug bioavailability. Modification of CPC with novel PLA/vancomycin microcapsules loaded and coated with nanosized hydroxyapatite resulted in 85.3±3.1% of vancomycin release within 43days.

Controlled release of local anesthetic from calcium phosphate bone cements.

Novel lidocaine containing calcium phosphate bone cements have been developed. Lidocaine release kinetics of these cements have been evaluated. Calcium phosphate cements have a great potential for local drug delivery. Release of local anesthetic, such as lidocaine, at the implant site can be useful for reducing pain immediately after implantation. In this work a local anesthetic - lidocaine hydrochloride - was incorporated into α-tricalcium phosphate cement. Lidocaine release profile was dependent on cement components used. All cements were characterized by an initial burst release, which can be correlated with cement pH values, followed by gradual drug release. Drug release continued for up to 6 days and was slower, if cement pH was higher. Addition of lidocaine hydrochloride accelerated setting and changed microstructure of the set cement.

Effect of Mg Content on Thermal Stability of β-Tricalcium Phosphate Ceramics

β-Tricalcium phosphate bioceramics with small, close to bone-like amounts of Mg were obtained by modified precipitation method and following sintering. The effect of small amounts of Mg on the thermal stability, microstructure and sintering behavior of β-tricalcium phosphate bioceramics was evaluated. Addition of small amounts of Mg, can induce a remarkable effect on the physic-chemical properties of β-TCP and therefore the chemical composition of the starting materials should be controlled.

Setting Properties of Brushite and Hydroxyapatite Compound Cements

In this work properties of potential brushite (CaHPO4•2H2O) and hydroxyapatite (Ca10(PO4)6(OH)2) compound cements are investigated. Calcium dihydrogenphosphate monohydrate (MCPM) and α-tricalcium phosphate (α-TCP) were the starting materials for investigated cements. Setting time is controlled by adding setting time retarder – citrate ions and initially unreactive filler - monetite (CaHPO4). Some compositions of obtained cements contain both brushite and hydroxyapatite. However a substantial amount of monetite was present even if it is not added as filler. There is a strong evidence of presence of octacalcium phosphate – a precursor phase for hydroxyapatite that lacks long range order.

The Influence of Biogenic and Synthetic Starting Materials on the Properties of Porous Hydroxyapatite Bioceramics

The aim of this study was to investigate the influence of biogenic and synthetic starting materials on properties of porous hydroxyapatite (HAp) bioceramics. HAp powders were synthesized by modified precipitation method using biogenic calcium carbonates (ostrich (Struthio camelus) egg shells, hen (Gallus gallus domesticus) egg shells, snail (Viviparus contectus) shells) and synthetic calcium oxides (Sigma-Aldrich and Fluka). Specific surface area, molecular structure and morphology of obtained powders were determined. As-synthesized HAp powders had a varied specific surface area with a wide range from 83 to 150 m2g-1 depending on CaO source. Porous bodies of HAp were prepared by in situ viscous mass foaming with NH4HCO3 as pore forming agent. Foamed and dried green bodies were sintered at 1100 °C. The obtained bioceramics were investigated using Archimedes method, field emission scanning electron microscopy and Brunauer-Emmett-Teller method. There are considerable differences between porous HAp bioceramics structures prepared from different sources of CaO. The choice of starting material substantially affects the macro-and microstructure of prepared porous bioceramics.

Fast Setting Pre-Mixed Calcium Phosphate Bone Cements Based on α-Tricalcium Phosphate

Conventional calcium phosphate bone cements are self setting water based pastes. Recently pre-mixed calcium phosphate bone cements have been proposed that have non-aqueous fluid as liquid phase of the paste. Such cements thus only start setting reaction in contact with body fluids. In this work the properties (cohesion, compressive strength, phase composition) of pre-mixed calcium phosphate cements based on α-tricalcium phosphate and calcium dihydrogen phosphate monohydrate are described. Properties of several cement compositions are examined and compared to properties of β-tricalcium phosphate and calcium dihydrogen phosphate monohydrate based cements. It was found that α-tricalcium phosphate and calcium dihydrogen phosphate monohydrate based cements have higher compressive strength (10 - 15 MPa) than corresponding β-tricalcium phosphate and calcium dihydrogen phosphate monohydrate based cements (10 - 6 MPa). Out of examined cement paste liquids (glycerol, polyethylene glycol and polypropylene glycol) cements using glycerol as the liquid phase had higher compressive strength and are more cohesive.

Calcium Phosphate Bone Cements Reinforced with Biodegradable Polymer Fibres for Drug Delivery

Conventional calcium phosphate bone cements are self setting water based pastes. Recently pre-mixed calcium phosphate bone cements have been proposed that have non-aqueous fluid as liquid phase of the paste. Such cements thus only start setting reaction in contact with body fluids. In this work the properties (cohesion, compressive strength, phase composition) of pre-mixed calcium phosphate cements based on α-tricalcium phosphate and calcium dihydrogen phosphate monohydrate are described. Properties of several cement compositions are examined and compared to properties of β-tricalcium phosphate and calcium dihydrogen phosphate monohydrate based cements. It was found that α-tricalcium phosphate and calcium dihydrogen phosphate monohydrate based cements have higher compressive strength (10 - 15 MPa) than corresponding β-tricalcium phosphate and calcium dihydrogen phosphate monohydrate based cements (10 - 6 MPa). Out of examined cement paste liquids (glycerol, polyethylene glycol and polypropylene glycol) cements using glycerol as the liquid phase had higher compressive strength and are more cohesive.

Synthesis of Amorphous Calcium Phosphate as a Starting Material for α-Tricalcium Phosphate

α-Tricalcium phosphate (α-TCP) is an important reactive component in calcium phosphate bone cements which are used for the bone tissue regeneration and augmentation. By thermally treating amorphous calcium phosphate (ACP) at relatively low temperatures (650–900 °C), it is possible to obtain sub-micrometre or nanosized α-TCP particles. In the current research, it is shown that the aqueous synthesis environment where ACP is precipitated has significant influence on the stability of ACP and the α-TCP content in the thermally treated products. During ACP synthesis pH must be kept basic. While it is possible to synthesize ACP if potassium hydroxide or sodium hydroxide is used to raise the pH of synthesis, ammonium ions also must be present in the solution to obtain α-TCP after thermal treatment of ACP. If sodium hydroxide is used, higher α-TCP content is obtained (compare 89 % and 66 %). Increase of Ca/P ratio stabilizes ACP and allows to obtain products with high α-TCP content. Increase of both calcium and phosphate ion concentration in the synthesis destabilizes ACP and reduces the amount of α-TCP in the product (twofold increase reduced α-TCP content from 89% to 2%).

Synthesis and Properties of α-Tricalcium Phosphate from Amorphous Calcium Phosphate as Component for Bone Cements

α-Tricalcium phosphate is an important ingredient of calcium phosphate bone cements, which are used for bone defect augmentation and repair. In this study sub-micrometre sized αtricalcium phosphate particles were synthesized by heat treating amorphous calcium phosphate. Size of synthesized particles depended on duration and temperature of heat treatment. Longer duration and higher temperatures produced larger particles. The reactivity of synthesized particles did not correlate with particle size – the smallest particles did not have the highest reactivity. The most reactive particles were prepared at 700-800 °C. The prepared particles were more reactive than those of conventionally synthesized α-tricalcium phosphate.

The Effect of α-Tricalcium Phosphate Powder Preparation Methods on Cement Properties

The properties of calcium phosphate cements are influenced both by presence of setting aids in cement paste and also by surface properties and particle size distribution of solid phase. In this study the influence of α-tricalcium phosphate powder preparation methods on properties of cement are examined: milling, thermal treatment at temperatures up to 600°C and treatment with deionized water. The properties of cements based on prepared powders evaluated are: setting time, injectability and cohesion. The compressive strength of selected cement samples was determined. Thermal treatment improves injectability, but significantly prolongs setting time and reduces cohesiveness. Treatment of powder particles with deionized water increases setting time, but also significantly reduces injectability. It was not possible to significantly increase powder liquid ratio (from 1.75 to 2.00), if thermally treated powders were used. It was found that reduction of particle size, under certain conditions, can increase the injectability of cements. Powder preparation methods do not significantly affect the compression strength of cement, but fast setting upon the contact water based fluids is necessary to obtain cohesive cements.