Moisture-Tolerant Polyurethane-Based Bone Cement Containing Enoxacin for the Sex-Specific Repair of Osteoporotic Defects

To address the challenges associated with bone cement curing in the presence of bleeding, a moisture-tolerant polyurethane-based cement was developed, demonstrating gender-specific therapeutic efficacy when repairing osteoporotic bone defects. The synthesized cements (PHE-1, PHE-2, and PHE-3) incorporated osteoinductive nano-hydroxyapatite (20 wt%) and varying concentrations of enoxacin (EN, 1–3 wt%) as an osteoclast inhibitor. These formulations exhibited moderate curing temperatures (36.8°C–40.7°C), maintained mechanical stability in the presence of blood, and achieved 99% monomer conversion within 240 min via moisture-triggered –NCO reactions. In vitro evaluations showed that PHE-2 effectively inhibited osteoclastogenesis in RAW 264.7 cells while simultaneously promoting osteogenic differentiation in bone marrow-derived mesenchymal stem cells. In vivo studies revealed more efficacious bone healing in ovariectomized rats compared to orchiectomized rats after 8 weeks of implantation. This difference was attributed to estrogen deficiency accelerating the degradation of the bone organic matrix, whereas androgen deficiency impaired biomineralization processes. Further mechanistic analysis indicated that gender-specific differences in bone turnover result from the enhanced matrix degradation induced by estrogen deficiency. Notably, PHE-2 effectively mitigated matrix-related pathologies associated with ovariectomies. This study highlights the importance of gender-specific approaches in managing osteoporotic bone defects and underscores the therapeutic potential of EN-loaded polyurethane cement for treating osteoporotic defects.