Gene Therapy for the Enhancement of Fracture Healing - Engineered Bone: Tissue Engineering Intelligence Unit - page 138

Table 1. Common carrier matrices employed for bone tissue engineering

C a r r i e r A d v a n t a g e s D i s a d v a n t a g e s E x a m p l e s R e f e r e n c e s

Inorganic Resembles natural Brittle Hydroxyapaptite, 133-137

materials structure of bone Difficult to mold porous coralline,

(calcium phosphates Exothermic hyaluronic acid,

Resorbable or calcium phosphate

nonresorbable cements, metals,

Binds BMP's and calcium sulfate

Synthetic Reproducible Degradation Poly ( α -hydroxy 133,138-145

polymers manufacture products may be toxic acids), polypropylene

Controlled release Cell recognition fumarate, polyanhydrides,

properties Solvents or polyphosphazenes,

Easy to sterilize crosslinkers may polyethylene glycol

damage proteins and poloxamers

Naturally- Extremely Disease transmission Fibrin glue, collagen, 133,146-149

derived biocompatible Difficult to sterilze chitosan and hyaluronic

polymers Possible natural Immune response acid

affinity for growth
factors
Composite Benefits depend Complex to Collagen-TCP, 133,150-153

materials on material manufacture collagen-HA

exploited and TCP cellulose

Applications

Fracture Healing
A large number of fractures are classified as high risk for potential nonunions or incomplete
unions. 154,155 There are many factors contributing to poor healing risk factors such as signifi-
cant soft tissue injury, anatomic location, velocity of impact plus others. 156-158 Poor fracture
healing is linked to chronic pain and prolonged ambulatory impairment and must often be
treated with an invasive operative procedure. 159 Currently, there are many treatments used to
enhance bone healing including autogenous or allographic bone grafts and various fixation
devices as mentioned previously. 154,156,160 Despite proper treatment being currently available,
lack of viable bone at the wound site and other adverse conditions may lead to structural
instability, possible infection and bone erosion. Current orthopedic treatments for defects of a
critical-size or severe complications that arise from common fractures lack an effective therapy
for complete healing in terms of restitutio ad integrum, evidenced by the frequent reported
complications. Recent progress has indicated that future enhancements will rely on applica-
tions of recombinant factors such as growth factors or cytokines known to stimulate bone
repair, and the use of ex vivo or in vivo delivery of these factors by gene therapy. 159 Although,
the use of recombinant proteins has been evaluated in a few human clinical trials, the use of
local gene therapy to deliver growth factors to the wound site has been limited to animal
models. 129,149,161-164 Recombinant BMPs (BMP-2, BMP-3, BMP-4, BMP-5, BMP-6) and
TGF- β can promote osteogenesis and bone healing in animal models and humans as shown in
a few, limited studies. 159 However, large doses (milligram amounts) of protein must be deliv-
ered to the wound site to achieve healing. This raises concern that therapeutic doses for hu-
mans would be expensive and include the additional risk of toxicity. Gene therapy for delivery
of growth factors to the defect site represents a more cost-effective solution. Further, cell-mediated
in vivo production of the protein will enhance protein functionality and localize expression to