A hybrid rhOP-1 delivery system enhances new bone regeneration and consolidation in a rabbit model of distraction osteogenesis

Abstract

The effect of an early single injection of biodegradable core-shell nanoparticles (NPs) loaded with various low doses of recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1) on new bone regeneration and consolidation in a rabbit model of tibial distraction osteogenesis (DO) was investigated. The Regenerate bone was examined using soft radiography, densitometry, micro-computed tomography and histomorphometry. Compared to control, higher bone fill scores and a two- to three-fold increase in the quantity of mineralized tissue were prominent in the 1.0 and 5.0 μg OP-1/NPs groups, 3 weeks post-injections (P>0.05). Histologically, the distraction gap was completely ossified and the osteotomy margins poorly demarcated in those groups, one week into the consolidation phase. An up-regulation of various growth factors, ligands, and receptors was observed using immunohistochemistry. This novel hybrid delivery system maintains the bioactivity of the encapsulant, minimizes the therapeutic doses of rhOP-1, and accelerates DO via its localized, release-controlled, osteogenic, and naturally biocompatible polymeric properties.

Keywords::

• Distraction osteogenesis
• osteogenic protein-1
• nanoparticles
• delivery systems
• bone densitometry
• histomorphometry

Acknowledgements

The authors would like to thank Dr Fereshteh Azari for her assistance with the cryo-TEM and Mrs Maria Kotsiopriftis and Mrs Dominique Lauzier for their assistance in histomorphometry and immunohistochemistry. This work was supported by an operating grant from the Shriners of North America, Fonds de la Recherche en Santé du Québec, the National Science and Engineering Research Council (NSERC), the Canadian Institutes of Health Research (CIHR) Regenerative Medicine/Nanomedicine, and the Center for Biorecognition and Biosensors (CBB), McGill University, Montréal, Québec, Canada. Dr Haidar acknowledges scholarships from the Center for Bone and Periodontal Diseases Research and the Shriners Hospital, Montréal, Québec, Canada.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.