A protonation/degradation dual control pH-responsive LVF delivery system with rod-shaped core-shell structure for the treatment of bone infections

Antibiotic-loaded poly(methyl methacrylate) (PMMA) bone cement was employed to inhibit bone infection and promote bone healing at the lesion site. However, there are several limitations, including a failure to release the antibiotic in response to the acidic environment of the bone infection, a mismatch between the drug release cycle and the healing cycle of human bone, inadequate mechanical strength, and inferior osteogenic properties. In this research, CaCO₃@P(HEMA-DMAEMA)-LVF (C@P-LVF) with a rod-shaped core-shell structure was synthesized and incorporated with PMMA bone cement to create C@P-LBC, a novel pH-responsive LVF delivery system achieved by the dual control mechanism of protonation/degradation of C@P-LVF and its unique rod-shaped structure. Simultaneously, the released calcium ions from C@P-LBC promoted mechanical properties and osteogenic properties. When the addition of C@P-LVF was 50 %, the cumulative release ratios of LVF from C@P-LBC were 34.08 ± 0.68 % and 65.52 ± 1.43 % at pH 7.4 and 5.5, respectively, representing a significant increase compared to PMMA bone cement. C@P-LBC also exhibited excellent pH-responsive antibacterial properties against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>. Meanwhile, the maximum compressive strength of C@P-LBC was 92.0 ± 1.7 MPa. Furthermore, C@P-LBC enhanced proliferation and stimulated early differentiation of osteoblasts. <i>In vivo</i> experiments confirmed that C@P-LBC promoted new bone formation and bone growth in bone defects. Additionally, C@P-LBC displayed superior <i>in vivo</i> antibacterial properties. Therefore, C@P-LBC emerged as a promising bone repair material to effectively facilitate the healing of bone tissue.