Development of fully-resorption replacement paste-like organic/inorganic artificial bones compatible with bone remodeling cycles

Abstract

Calcium-phosphate cement (CPC), commonly used as a bone graft substitute, sets as hydroxyapatite (HAp) and remains in the body for extended periods. To enhance bioresorbabability, we developed a chelate-setting tricalcium β-phosphate (β-TCP) cement using inositol phosphate (IP6) surface modification. By incorporating poly(lactic-co-glycolic acid) (PLGA) particles as a pore-forming agent and calcium sulfate hemihydrate (CSH) to this CPC, we created an organic/inorganic hybrid cement combining bioresorbability with favorable material properties. In this study, varying amounts of PLGA particles were added alongside CSH, and the resulting cement's properties, cytotoxicity, and in vivo response large animals (pigs) were assessed. The cement exhibited a compressive strength of ∼ 30 MPa and set within 15 min, making it suitable for clinical use. Cytotoxicity tests using Transwell® demonstrated cell growth in all cement specimens. In a pig tibia model, the amount of PLGA particle of 5 mass%, 10 mass%, and 20 mass% were tested to optimize material resorption and bone formation, compared with commercial HAp-based CPCs. Histological evaluations showed that higher amount of PLGA particles (10 mass% and 20 mass%) led to increased material resorption but impaired bone formation. The cement containing 5 mass% PLGA particles achieved the best balance, promoting the highest rate of bone formation. Thus, 5 mass% PLGA is the optimal amount for balancing resorption and bone regeneration in β-TCP cement. This formulation is expected to serve as a fully absorbable hybrid paste-type artificial bone supporting bone remodeling cycles.