Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy


Structural allograft healing is limited because of a lack of vascularization and remodeling. To study this we developed a mouse model that recapitulates the clinical aspects of live autograft and processed allograft healing. Gene expression analyses showed that there is a substantial decrease in the genes encoding RANKL and VEGF during allograft healing. Loss-of-function studies showed that both factors are required for autograft healing. To determine whether addition of these signals could stimulate allograft vascularization and remodeling, we developed a new approach in which rAAV can be freeze-dried onto the cortical surface without losing infectivity. We show that combination rAAV-RANKL- and rAAV-VEGF-coated allografts show marked remodeling and vascularization, which leads to a new bone collar around the graft. In conclusion, we find that RANKL and VEGF are necessary and sufficient for efficient autograft remodeling and can be transferred using rAAV to revitalize structural allografts.

DOI: 10.1038/nm1190
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@article{Ito2005RemodelingOC, title={Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy}, author={Hiromu Ito and Mette Koefoed and Prarop Tiyapatanaputi and Kirill Gromov and J. Jeffrey Goater and Jonathan J. Carmouche and Xinping Zhang and Paul T. Rubery and Joseph E. Rabinowitz and Richard Jude Samulski and Takashi Nakamura and Kjeld Soballe and Regis J O'keefe and Brendan F . Boyce and Edward M. Schwarz}, journal={Nature Medicine}, year={2005}, volume={11}, pages={291-297} }