Development of paste-like organic/inorganic artificial bones compatible with bone remodeling cycles, consisting of β-tricalcium phosphate, calcium sulfate hemihydrate, and poly(lactic-co-glycolic acid) particles

Abstract

Calcium-phosphate cement (CPC) is currently used to treat bone defects; however, it may cause inflammation due to pH changes by acid–base reactions during setting. Therefore, we have developed bioresorbable chelate-setting β-tricalcium phosphate (β-TCP) cement based on surface modification of inositol phosphate (IP6). In order to improve the bioresorbability, we have previously succeeded in preparing IP6/β-TCP cement hybridized with poly(lactic-co-glycolic acid) (PLGA) particles as a pore-forming agent. However, the hybrid cement had a prolonged setting time. In this study, calcium sulfate hemihydrate (CSH) was added to shorten the setting time and further improve the cement bioabsorbability, and the material properties of the resulting samples were clarified, together with an in vivo reaction. The cement setting time with the simultaneous addition of 10 mass% PLGA particles and CSH was successfully reduced from 26.3 min, the cement setting time without CSH addition, to 15 min; and the compressive strength of the cement was 30 MPa or higher. The hard tissue compatibility of the resulting cement was qualitatively evaluated using a rat calvaria defect model. Subsequently, the bioresorption and bone formation rates of the cement were quantitatively determined using large animal pigs, which are more similar to humans in terms of their in vivo response. The highest bioabsorption (39.6%) and bone formation rates (24.2%) were confirmed for cement with the simultaneous addition of 10 mass% PLGA particles and CSH. Organic/inorganic hybrid cement with the simultaneous addition of CSH and PLGA particles is expected to be clinically applicable as a bone repair cement with a short setting time, improved compressive strength, and bioresorbability compatible with the bone remodeling cycle.