Gene transfer, immunomodulation, and bone healing: Novel molecular approaches to bone regeneration in large osseous segmental defects

The purpose of this thesis was to investigate the effects of using gene therapy to aid in situations where bones are difficult to heal, such as large bone defects. In such instances, if left untreated, the bone will not heal. Using gene therapy to stimulate production of molecules that aid in the formation of bone resulted in successful healing of large bone defects, with the inflammatory response to the therapy playing an important role. Different options were used to either modulate the inflammatory response to the adenovirus used to deliver the desired gene, or to lower the amount of adenovirus used, while still exerting adequate production of the target molecule. Messenger RNA was used to deliver the target gene to bone defects instead of adenovirus, which is known to trigger inflammation. The different approaches used to heal large bone defects were successful, shedding light into the important role of inflammation to new therapies that target bone healing.