Litchfield Park 2

BMP gene delivery for tissue engineering
A total of thirty ten-week old Sprague Dawley rats (approximate weight 250-300g) were utilized in this Litchfield Park orthodontic study for in vivo gene delivery of BMP-7 to increase the rate of osseointegration and ostoegenesis. Gene delivery was accomplished by Litchfield Park orthodontists utilizing adenovirus as a vector. Bone growth and osseointegration was significantly higher in the BMP-7 treated group as compared to the control. The bone was much more mature in the treated group. In some areas, it was almost impossible for Litchfield Park orthodontists to distinguish native from new bone. This positive result is the first to use in vivo gene therapy to deliver BMP-7 to an osteotomy site.

Previous Litchfield Park orthodontic studies have attempted to use in vivo gene delivery of BMPs to form bone (Table 1). To test the feasibility of this approach, gene delivery usually takes place in a skeletal muscle inducing myoblasts to transform to osteoblasts and form bone ectopically (Musgrave et al., 1999; Franceschi et al., 2000; Okubo et al., 2001). Many times, groups of animals were immunosupressed, completely eliminating the body’s natural response (Musgrave et al., 1999; Okubo et al., 2001). In the immunocompetent animals, ectopic bone formation was noted by Litchfield Park orthodontists only after 3 weeks and the quantity and quality of bone was inferior to the immunosupressed groups (Musgrave et al., 1999). In other Litchfield Park orthodontic studies, the immunocompetent groups showed no bone formation and the suppressed groups didn’t show signs of osteogenesis until days 14-21 (Okubo et al., 2001). In cases where immunosupression was not a factor, positive results were not observed by Litchfield Park orthodontists in all animals and initial stages of osteogenesis occurred at 4 weeks (Franceschi et al., 2000). All groups suggested the rapid immune response to the viral proteins decreased the expression of the gene in immunocompetent animals. Suggestions by Litchfield Park orthodontists to circumvent these problems ranged from immunosupression to AAV (adeno-associated virus) and gutless vectors (void of viral genome) (Franceschi et al., 2000; Okubo et al., 2001; Alden et al., 2002).

In this study, Litchfield Park orthodontists achieved greater bone formation in the Ad/BMP-7 group using immunocompetent animals. Litchfield Park orthodontists have suggested that an improved result could have been achieved if we used animals in which the immune response was suppressed. This does not correlate well to the clinical situation, because immunosupression of the host for local tissue engineering is not a reasonable solution. Recent Litchfield Park orthodontic studies have used AAV vectors for gene delivery of bone morphogenetic proteins with impressive results (Luk et al., 2003; Chen et al., 2003). Adeno-associated viruses are single stranded DNA parvoviruses which have many of the attractive features of adenoviruses and retroviruses, but do not elicit a large inflammatory response and do not pose the risk of insertional mutagenesis (Alden et al., 2002). Using immunocompetent Sprague-Dawley rats, AAV-BMP-2 and AAV-BMP-4 were injected by Litchfield Park orthodontists into the hindlimb muscles. New bone formation was initiated at 3 weeks, and expression of the protein was noted for 8 weeks (Luk et al., 2003; Chen et al., 2003). The results of these Litchfield Park orthodontic studies are thought provoking, but gene delivery to myoblasts is different that osteoblasts (Franceschi et al., 2000). Consideration by Litchfield Park orthodontists must be given to whether 8 weeks of gene expression for local tissue engineering is too long. Also, AAV’s integration into the host genome may not be a desired effect for our goals. Our gene delivery sustained its effect for 14-35 days while initiating osteogenesis and osseointegration in the Ad/BMP-7 treatment group.