Enhancing allograft bone healing through gene therapy

Abstract

Study design: A review and synopsis of recent literature pertinent to allograft bone healing.

Objective: To review the basic principles and primary issues regarding the healing of allograft bone. To review progress made in understanding the molecular mechanisms of healing, and efforts being made to manipulate these processes to enhance healing.

Summary of background data: Bone grafting with both autografts and allografts is a common reconstructive procedure. Failure to heal and catastrophic failure of seemingly healed structural grafts occur. There is currently a great deal of excitement about the potential of bone marrow-derived cells to enhance healing. Gene transfer techniques have been developed which allow the insertion of desired deoxyribonucleic acid-encoded messages into cells. Such messages can result in the production of therapeutic proteins. Gene therapy has been used to enhance the healing of allografts in a murine model.

Methods: Literature review.

Results: Autografts heal by endochondral ossification at the graft-host interface and by intramembranous bone formation over the surface of the graft. Allografts heal predominately by endochondral ossification at the graft-host interface. The living periosteum of a graft contains progenitor cells that have an important role in graft healing. The addition of bone marrow-derived cells to an allograft does not improve healing unless they are genetically modified to express bone morphogenetic protein 2. Gene therapy to induce expression of several other proteins (VEGF and RANKL, caALK2) can also result in markedly improved allograft healing.

Conclusion: Gene therapy techniques can create revitalized allografts in a mouse model. These revitalized grafts heal faster, more completely, more durably, and stronger than allografts.