Gene Therapy for the Enhancement of Fracture Healing - Engineered Bone: Tissue Engineering Intelligence Unit - page 137

Figure 3. The three main strategies for growth factor delivery to cells. a) Gene therapy: The gene of interest
is transferred directly to the body either alone or with a non-viral or viral vector. b) Cell therapy: DNA is
transferred to the cells in vitro and cultured before transplantation back into the patient. c) Protein therapy:
The growth factor is directly injected into the patient or delivered via a carrier matrix.
These are primary constituents of bone matrix and are known to naturally bind BMPs and
other potential osteoinductive factors within the ECM. 132 Unfortunately, the most cost-efficient,
easy to manufacture, well-characterized materials are not natural; they are often easily-sterilized
synthetic polymers. Examples of matrix materials and their properties are shown in Table 1.
Scaffolds further contribute to the re-creation of the “natural microenvironment” of bone
formation. Host or seeded cultured cells infiltrate the scaffold and respond to the endogenous
molecular cues or those enhanced by gene, cell or protein therapy. The proper combination of
cells, signals and matrices promotes effective and successful bone healing. Much more research
must be done to fully characterize the basic biology behind bone formation. However, since we
know that certain growth factors exist that promote bone regeneration (TGF- β , FGF, PDGF,
IGF, BMPs); we can begin to focus on mimicking Mother Nature's design of the bone mi-
croenvironment using the information known. Protein therapy (especially with BMPs) using
carrier matrices is the most widely used and researched treatment; however the many disadvan-
tages mentioned above lead scientists towards gene and cell therapy techniques for bone tissue
engineering. Growth factor delivery to the wound site via gene or cell therapy overcomes many
of the obstacles faced with protein therapy. The potential success of gene therapy strategies in a
future clinical trials are evidenced in studies conducted both in vitro and in animal models for
bone defects. Attempts to heal common bone defects using gene therapy are discussed below.
The relative successes and failures of gene therapy for bone healing are addressed. The future of
gene therapy and the ultimate healing of bone defects are dependent on scientists' abilities to
overcome the obstacles faced when attempting to heal bone defects. Reengineering the bone
microenvironment can be achieved through gene therapy by first understanding the funda-
mental biology of bone, the ECM and limitations of gene therapy. However, with each bone
defect or disease, a unique situation exists, complete with different physiologies, pathologies
and dynamics which directly influence the success of the gene therapy methods employed.