Marina Sokolova

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.

Scale-up of Wet Precipitation Calcium Phosphate Synthesis

Within current research calcium phosphates were synthesized by wet chemical precipitation method in laboratory and pilot scale reactor. The aim of this work was to study the influence of main technological parameters of wet chemical precipitation synthesis and scale-up of laboratory synthesis. The results showed that it is possible to obtain calcium phosphates with different and reproducible phase compositions such as hydroxyapatite (HAp), β-tricalcium phosphate (β-TCP) and biphasic calcium phosphates (HAp/β-TCP) in pilot scale reactor. Using the method developed it was possible to increase the product yield more than 30 times compared to formerly used laboratory scale method.

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.

Mechanical Properties and Biocompatibility of a Biomaterial Based on Deproteinized Hydroxyapatite and Endodentine Cement

Abstract Hydroxyapatite is used for bone reconstruction, in order to improve its mechanical properties different substances can be added. In our study new biomaterial is created from deproteinised hydroxyaptite and endodentic cement, its mechanical properties were tested. Material was implanted subcutaneous in rats, then histological and biocompatability tests were performed. Results indicate that stuff has good mechanical properties, short setting time and gradual resorption creating porosity and ability to integrate in bone.

Microencapsulation of mildronate in biodegradable and non-biodegradable polymers.

Abstract The extremely high hygroscopicity (solubility in water ≥2 g/ml) of the pharmaceutical preparation mildronate defines specific requirements to both packaging material and storage conditions. To overcome the above mentioned inconveniences, microencapsulated form of mildronate was developed using polystyrene (PS) and poly (lactic acid) (PLA) as watertight coating materials. Drug/polymer interaction as well as influence of the microencapsulation process variables on microparticle properties was studied in detail. Water-in-oil-in-water double emulsion technique was adapted and applied for the preparation of PS/mildronate microparticles with total drug load up to 77 %wt and PLA/mildronate microparticles with total drug load up to 80 %wt. The repeatability of the microencapsulation process was ±4% and the encapsulation efficiency of the active ingredient reached 60 %wt. The drug release kinetics from the obtained microparticles was evaluated and it was found that drug release in vivo could be successfully sustained if polystyrene matrix has been used.

Antibacterial Efficiency of Hydroxyapatite Biomaterials with Biodegradable Polylactic Acid and Polycaprolactone Polymers Saturated with Antibiotics / Bionoārdāmu Polimēru Saturošu Un Ar Antibiotiskajām Vielām Piesūcinātu Biomateriālu Antibakteriālās Efektivitātes Noteikšana

Abstract Infections continue to spread in all fields of medicine, and especially in the field of implant biomaterial surgery, and not only during the surgery, but also after surgery. Reducing the adhesion of bacteria could decrease the possibility of biomaterial-associated infections. Bacterial adhesion could be reduced by local antibiotic release from the biomaterial. In this in vitro study, hydroxyapatite biomaterials with antibiotics and biodegradable polymers were tested for their ability to reduce bacteria adhesion and biofilm development. This study examined the antibacterial efficiency of hydroxyapatite biomaterials with antibiotics and biodegradable polymers against Staphylococcus epidermidis and Pseudomonas aeruginosa. The study found that hydroxyapatite biomaterials with antibiotics and biodegradable polymers show longer antibacterial properties than hydroxyapatite biomaterials with antibiotics against both bacterial cultures. Therefore, the results of this study demonstrated that biomaterials that are coated with biodegradable polymers release antibiotics from biomaterial samples for a longer period of time and may be useful for reducing bacterial adhesion on orthopedic implants.

Hyaluronan Hydrogel/Calcium Phosphates Composites for Medical Application

The combination of calcium phosphate compounds and hyaluronan is expected to have advantages of both materials to be used as optimal scaffold for bone tissue engineering. It possesses the fundamental necessary characteristics such as bioactivity, biomechanical similarity, processability, and biodegradability. Preparation technology and properties of hyaluronan acid and calcium phosphate composites (HA/CaP) are described in the current study, and for the first time composites with high, up to 0.43 HA/CaP mass ratio are synthesized using chemical cross-linking method.HA/CaP hydrogels were prepared using fixed cross-linker amount at different HA concentrations. Swelling properties of prepared HA/CaP hydrogels were investigated as function of the HA content in composite. The swelling properties of hydrogels were studied in phosphate-buffered saline (PBS) at pH 7.4. It was observed that HA reinforcement with CaP particles increases hydrogel stability, and prepared HA/CaP hydrogels maintained their integrity up to 4 weeks.

The Level of Inflammatory Cytokines and Antimicrobial Peptides after Composite Material Implantation and Contamination with Bacterial Culture

As biomaterial implantation is a traumatic process, especially if the implanted object becomes contaminated by bacteria, it can cause a significant increase in the production of inflammatory cytokines. An increase in the level of inflammatory cytokines can be used as a marker of biomaterial associated infection (BAI) in surrounding tissues. To prevent BAI and production of inflammatory cytokines, biomaterials with antibiotics should be used, in particular biomaterials with prolonged release of antibiotics. In this in vivo study, the level of inflammatory cytokines (interleukine – 10 (IL-10), beta-defensin-2 and tumor necrosis factors (TNF-alpha)) was determined in surrounding tissues after composite material implantation in vivo and wound contamination with Staphylococcus epidermidis (S. epidermidis) or Pseudomonas aeruginosa (P. aeruginosa). The results show that the level of inflammatory cytokines is normal in surrounding tissues after implantation of biomaterials with prolonged release of antibiotics. Biomaterials with rapid release of antibiotics also show normal levels of inflammatory cytokines. The level of inflammatory cytokines increases in cases if biomaterials without antibiotics are implanted in vivo, thus being an indication of inflammation process and BAI.