Combined improvement of osteogenic and anti-inflammatory activities of Sr-doped bone cement modified with carboxymethyl cellulose

Abstract

Incorporating strontium into bone cement is an effective way for bone repair. Macrophages play an essential role during implant osseointegration. However, whether carboxymethyl cellulose (CMC) modifying Sr-doped bone cement can jointly enhance M2 polarization and osteogenic differentiation remains unknown. To further explore this hypothesis, we introduced CMC into the hydration process of calcium sulfate hemihydrate, strontium oxide, and calcium phosphate monobasic monohydrate to form biodegradable composite bone cement (CMC/SPC). The operability and physicochemical properties of CMC/SPC can be adjusted by formulation parameters, including CMC content and the corresponding L/P ratio required for paste formation. In vitro and in vivo experiments showed that 40%CMC/SPC induced anti-inflammatory M2 macrophage phenotypes and degraded approximately 90% in vivo within 12 weeks. 40%CMC/SPC extracts upregulated the expression of osteogenesis-related genes. Micro-CT and histological analysis revealed that 40%CMC/SPC had superior bone regeneration without significant systemic toxicity in vivo. Overall, the present study indicates that CMC/SPC may provide a favorable microenvironment associated with anti-inflammatory macrophage polarization and enhanced bone formation, suggesting its potential as a candidate material for bone defect reconstruction.