Gene Therapy for the Enhancement of Fracture Healing - Engineered Bone: Tissue Engineering Intelligence Unit - page 144

Figure 7. Doxycycline can be used to regulate exogenous rhBMP-2 expression in vivo and promote bone
healing a) In the prescence of Dox, no rhBMP-2 is produced, whereas, no Dox promotes rhBMP-2
expression in C9 cells. b-d) MicroCT was used to scan mouse forelimbs with bones and muscles intact.
Three-dimensional reconstructions (b and c) and simulated x-ray projection images (d and e) show that in
the absence of doxycycline, new bone is formed at the defect site.
Considerations When Devising a Gene Therapy Strategy for Bone
To treat any bone defect, the physician must consider the many factors: the nature of the
defect, the condition of the soft tissue surrounding the wound site, and the overall health of the
individual. Gene therapy may be a good choice for wound repair if the host tissue surrounding
the wound is viable and healthy. When designing a gene therapy strategy, one must consider
the target tissue or cells, the duration of gene expression required (Fig. 8), and the protein
being expressed.
To achieve optimal bone healing, a clearer understanding of basic bone biology must be
reached. Although, we know of many osteoinductive factors that can enhance the new bone
formation, we most certainly do not have the entire bone microenvironmental network charac-
terized. We must strive to identify signaling molecules other than the BMPs and TGF- β that
contribute to osteogenesis. Additional in vitro and in vivo animal studies must be conducted to
further identify gaps in basic knowledge before clinical trials in humans can be conducted. As
we gain specific knowledge of the bone microenvironment and understand how the signaling
molecules cooperate functionally to promote osteogenesis, gene therapy strategies can coevolve
to derive the ideal bone tissue engineering therapy.
With continuing advances in gene technology, gene therapy will likely become increasingly
important in healing both acute and chronic wounds/pathologies. As our understanding of the
physiology of bone fracture repair and the role of the various repair regulators at the molecular
level increases, this will ultimately accelerate the progress of gene therapy. In addition, the
transfection efficiency and the safety of the delivery systems is expected to improve, providing
a clinically feasible therapy.