Preparation and osteogenic performance study of troxerutin-loaded carboxymethyl cellulose/Si-calcium phosphate cement composite bone cement

Abstract

Bone defects from trauma, infection, and tumour resection are a growing clinical challenge due to global population aging. Current treatments like autologous and allogeneic bone grafting have limitations. This study focused on optimizing ion-doped α-tricalcium phosphate (α-TCP) preparation and developing calcium phosphate cement (CPC) with superior physicochemical and biological properties. Calcium pyrophosphate (CPP) and calcium carbonate (CaCO₃) showed the highest conversion efficiency during synthesis. Adding SiO₂ to this combination generated high-purity silicon-doped α-TCP (Si-α-TCP) powder at 1200 °C. To enhance CPC's performance, different amounts of sodium carboxymethyl cellulose (CMC) were added to the setting liquid. The CMC/Si-CPC with 1 %wt CMC demonstrated the best physicochemical properties, with improved setting time, compressive strength, injectability, and anti-dispersion. In drug-loading experiments, CMC promoted the release of Troxerutin (TRO), showing burst release within 6 h followed by sustained release. In vitro experiments with MC3T3-E1 cells confirmed good biocompatibility and osteogenic activity, further enhanced by Si-ion doping and 0.5 mg/mL TRO in the setting liquid. In vivo experiments, including rat subcutaneous and rabbit femoral defect implantation, confirmed effective osteoconductivity and osseointegration without inflammation or necrosis. In conclusion, this study successfully prepared high-purity Si-α-TCP powder by optimizing raw material combinations and Si-ion doping. CMC improved CPC's physicochemical properties, while Si-ion doping and TRO loading enhanced its biocompatibility and osteogenic activity. TRO/CMC/Si-CPC is promising for bone defect treatment and offers a new concept for bone tissue engineering materials.