Antibiotic-loaded Calcium Phosphate Cement/Biodegradable Polymer Composites for Bone Repair
Z. Irbe (Sp), D. Loca, J. Gulbis, Riga Technical University (Latvia); N. Romancikova, Latvian Institute of Organic Synthesis, Riga (Latvia); L. Berzina-Cimdina, D. Vempere, Riga Technical University (Latvia)  
 
Calcium phosphate cements (CPC) are bioactive, biocompatible and osteoconductive biomaterials for bone repair. Bone regeneration and CPC resorbtion can be promoted by introducing biodegradable polymer microparticles into cement. Polymer microparticles provide mechanical stability at the beginning of implantation, macroporosity after particle resorbtion and can serve as depot for sustained release of antibiotics. Resorbtion rate of cement can be modified by changing its composition.
In this work alpha-tricalcium phosphate, sodium phosphate buffers and various additives for setting process modifications are used as starting materials for CPC preparation. Phase composition of CPC changes significantly in first hours and days after setting. Phase composition is highly dependent on initial pH of the liquid phase and overall Ca/P ratio of the cement. During cement setting only the outer shell of alpha-tricalcium phosphate particles reacts. If the liquid phase of the cement is strongly acidic, dicalcium phosphate forms upon setting. If the liquid phase of the cement is near neutral (pH 7 – 9) Ca-deficient hydoxyapatite forms. Within 3 – 4 days both types of cement fully transform to nanostructured Ca-deficient hydroxyapatite. The cements show good processability – are paste-like for up to 8 min at 21°C and set in 1 - 3 min after exposure to 37°C. In vitro acellular simulated body fluid and cell culture studies reveal the bioactivity and biocompatibility of the cements.
Antibiotic-loaded biodegradable polymer microparticles were fabricated using water-in-oil-in-water emulsion technique. Drug release kinetics from non-composite cements, composite cements and standalone microparticles was compared and are highly dependent on CPC composition and antibiotic properties. Drug release from non-composite cements is characterized by initial ‘burst’. For composite cement ‘burst’ is significantly reduced when compared to non-composite cement and standalone microparticles.