2.6. Gene therapy in a bone defect model

Bone morphogenetic protein can induce bone in a bone defect, but the missing ideal carrier system for BMPs limits their clinical application. Modern gene technology has been able to create BMP-producing cells, which can be used to heal bone defects. Gene therapy offers several potential advantages over other methods of osteoinduction, and current research suggests that it may be a treatment option for the ortopedic surgeon in the near future (Scaduto & Liebermann 1999).

Fang et al. (1996) used a rat bone defect model with a BMP-4 cDNA construct, which was delivered to the defect by loading on a gene-activated matrix, and the 5 mm defects healed. In another study using gene therapy, Lieberman et al. (1999) filled a 8 mm rat femoral bone defect with BMP-2 producing bone marrow cells created by means of adenoviral gene transfer. They found solid bony healing of the defect, and bone formation was more prominent in gene therapy treated defects compared to those treated with rhBMP-2 in a DBM carrier. The authors propose that the osteoinductive stimulus associated with the BMP-2-producing bone marrow cells may be enhanced because the BMP-2 protein is released continuously.

Gene therapy may also be a possible future treatment for difficult fractures and non-unions along with other modes of treatment (Niyibizi et al. 1998).

Athough the results of gene therapy seem to be promising, there are still many unanswered questions, such are the duration and amount of protein production in vivo, the safety of the viral vector, the immunological response to viral proteins, and the fate of BMP-producing cells after implantation. The research in this field is obviously of great interest and we might find answers to these questions in the future.