The role of gene therapy for craniofacial and dental tissue engineering

Basic science advances in bone tissue engineering using osteoinductive protein therapy have already been translated to the use in patients with selected orthopedic problems. The story of the development of bone morphogenetic protein (BMP) osteoinductive therapy, from the discovery of this class of molecules in 1965 to the publication of randomized clinical trials in 2001 for tibial non-unions and 2002 for spinal fusion, is truly fascinating. Both clinical studies showed healing equivalence of the BMP-bioimplant compared to a free non-vascularized bone graft but without the associated donor site morbidity. These advances unfortunately have not lead to rapid application of using BMP osteoinductive protein therapy for reconstructing most craniofacial bone defects, with clinical case series beginning to be reported only for limited small-sized defects. This is a reflection of the complexity and unique characteristics of most craniofacial defects, which will likely require a more robust osteoinductive signal than delivering recombinant protein on a scaffold for clinically meaningful bone regeneration. Gene therapy approaches are promising for overcoming the unique challenges that are characteristic of craniofacial and dental defects.