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Abstract
Purpose
LLP2A-alendronate (LLP2A-Ale) is a novel bone-seeking compound that recruits mesenchymal stem cells to the bone surface and stimulates bone formation. The purpose of this study was to investigate the efficacy of LLP2A-Ale in the treatment of rabbit open fracture.
Methods
Thirty New Zealand White rabbits underwent radius mid-diaphyseal osteotomy and were randomly divided into control and treatment groups with fifteen rabbits in each group. The treatment group received only one injection of LLP2A-Ale (dosage 125 μg/kg), whereas the control group received one injection of PBS. X-ray images were taken to observe the course of fracture healing at 2, 4 and 6 weeks after treatment. Rabbits were sacrificed at 4 and 6 weeks post treatment. Calluses were then harvested and were subjected to histology, immunohistochemistry, molecular biology techniques and biomechanical test.
Results
X-ray images showed that the LLP2A-Ale group exhibited abundant callus formation, stronger bony callus remodeling and earlier marrow cavity recanalization compared to the control group in a time-dependent manner. Histomorphological analysis revealed an advance in woven formation at 4 weeks and lamellar bone formation at 6 weeks in the LLP2A-Ale group. Moreover, gene and protein levels suggested that LLP2A-Ale promoted osteogenesis and angiogenesis probably via upregulating the expression of osteogenesis factors (including bone morphogenetic protein 2 and Runt-related transcription factor 2) and angiogenesis factors (vascular endothelial growth factor). Besides, the radius callus biomechanical properties were significantly enhanced in the LLP2A-Ale group compared with the control group at 6 weeks.
Conclusion
LLP2A-Ale can significantly promote open fracture healing in the rabbit model, probably through enhancing osteogenesis and angiogenesis.
Acknowledgments
We thank Prof Kit S Lam and Prof Yu Aiming (Department of Biochemistry and Molecular Medicine, University of California at Davis Medical Center) for providing LLP2A-Ale. The work was funded by Wuhan Clinical Medical Research Center of Microsurgery.
Disclosure
The authors report no conflicts of interests in this work. Dr Dong Zhang, Dr Baiwen Qi, Dr Weidong Xiao, Dr Xiang Hu, and Dr Aixi Yu report grants from Wuhan Clinical Medical Research Center of Microsurgery during the conduct of the study.