Beta-tricalcium phosphate particles as a controlled release carrier of osteogenic proteins for bone tissue...

Beta-tricalcium phosphate (β-TCP) has been widely used as bone substitutes and delivery carriers of osteogenic proteins. However, low protein carrying capacity and agent burst release profiles of β-TCP limit their usage. This study investigates strategies to enhance protein carrying capacity of β-TCP particles with reduced initial burst by surface etching in citric acid solution or by creating apatite coatings with the simulate body fluid immersion approach. The release kinetics of protein from the modified β-TCP particles was investigated using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein. Although chemical etching treatments reduced the initial burst release of protein from the particles, a rapid burst release was observed with high protein dose. In contrast, the burst release of protein was significantly reduced by the apatite coating and a high protein dose was successfully delivered over a prolonged period from the apatite-coated particles. Protein release was further modulated by simultaneously delivering proteins from two different substrates: acid-etched and apatite-coated particles. The bioactivity of the protein was preserved during the loading procedure onto the particles. In addition, protein-loaded particles maintained biological activity in the lyophilized state over 4 weeks. These findings suggest that the protein carrying capacity of β-TCP can be modulated by surface modification, which has a potential for use as a protein carrier with controlled release.