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© Tian et al. 2015. Background: The major disadvantage of using a stem cell-based bone morphogenetic protein-4 (BMP4) gene therapy for skull defect is the overgrowth of generated bone tissue in situ. In the present study, to overcome bony overgrowth of stem cell based-gene therapy, a new strategy of two-stage bone tissue engineering by an adeno-associated virus containing BMP4 gene (AAV-BMP4) gene therapy was used. Methods: AAV-BMP4 was purposely implanted in the skeletal muscle of mice to generate ectopic bone tissues during the first stage. Next, the newly formed ectopic bone tissues were harvested and then transplanted to repair the mouse skull defect during the second stage. Results: The results showed that skeletal muscle implantation of AAV-BMP4 yielded a large amount of new bone tissues. The ectopic bone tissues can be harvested as a bone graft and can successfully repair the mouse skull defect without any bony overgrowth in situ. Conclusion: The results indicate that the bone tissues purposely generated by AAV-BMP4 in the skeletal muscle may be a new alternative of bone grafting for clinical purposes

journal of orthopaedic surgery and research

Two-stage therapeutic utility of ectopically formed bone tissue in skeletal muscle induced by adeno-associated virus containing bone morphogenetic protein-4 gene