Delivery of growth factors using gene therapy to enhance bone healing

To review the delivery of growth factors using gene therapy for enhancing long-bone fracture healing.

Literature review.

MEDLINE and CAB Abstracts literature search (1980-2004).

Non-union and infected non-union are relatively common complications of long-bone fractures in human and veterinary patients. Growth factors are cytokines that regulate many cell functions important in fracture healing. Exogenous growth factors can be delivered to the fracture site as recombinant proteins or using gene therapy. Recombinant human bone morphogenetic protein-2 and -7 (rhBMP-2 and -7), in particular, enhance fracture healing in numerous experimental and clinical studies. Some limitations with use of recombinant proteins may be overcome by use of gene therapy. Gene therapy involves delivery of the growth factor gene to cells at the fracture site using a viral or non-viral vector. The gene is then expressed (protein synthesis) by cells at the fracture site. Delivery of the BMP gene to the fracture site using gene therapy has been evaluated in laboratory animal models of non-union, with favorable results and without complications.

Delivery of growth factors, particularly members of BMP family, to the fracture site using gene therapy may be a method to enhance fracture healing. Use of this technology may improve the prognosis for patients with long-bone fractures.

Clinical application of gene therapy could improve the prognosis for human and veterinary patients with long-bone fractures, but has not been evaluated clinically.