Propofol nanoparticles promote fracture healing in mice by accelerating cartilage formation

Background: Fracture healing is a process characterized by cartilage formation and subsequent ossification. Propofol, a systemic anesthetic known for its anti-inflammatory and chondrogenic properties, was encapsulated into nanoparticles (NPs) to improve its therapeutic efficacy. This study investigates the impact of these nanoparticles on fracture healing in a murine model. Methods: Propofol-NPs were synthesized and administered in a mouse femoral fracture model. Post-fracture, mice were randomly allocated to control, propofol, or propofol-NPs groups, with the latter receiving daily intraperitoneal injections. Fracture healing was evaluated through Hematoxylin and Eosin (HE) and Masson’s trichrome staining, along with motor function assessments. In vitro, bone marrow-derived mesenchymal stem cells (BMSCs) were induced to differentiate into chondrocytes, and propofol’s effects on differentiation were analyzed. Additionally, cell migration was assessed via scratch and Transwell assays. Western blot analysis was performed to quantify the expression of bone morphogenetic protein (BMP)2, aggrecan, Collagen Type II Alpha 1 Chain (Col2a1), activin receptor-like kinases (Alk)2, osterix (OSX), β-catenin, and collagen I (COL1) in differentiated BMSCs. Results: Propofol treatment significantly accelerated fracture healing and improved bone quality compared to the control group (p < 0.01). The propofol-NPs group exhibited a marked enhancement over the propofol group (p < 0.05). Both treatments facilitated BMSC differentiation into chondrocytes and upregulated key differentiation markers (p < 0.01). BMP2, aggrecan, Col2a1, activin receptor-like kinases (Alk)2, and phosphorylated β-catenin (p-β-catenin) levels were significantly increased after propofol and propofol-NPs treatment (p < 0.01), with OSX and COL1 also upregulated. Propofol-NPs demonstrated superior therapeutic efficacy over propofol alone. Conclusions: Propofol-NPs enhance fracture healing in mice by promoting cartilage formation and BMSC differentiation, offering promising potential for clinical applications in fracture repair.