BMP Gene Delivery for Bone Engineering at Dental Implant Defects

BMP Gene Delivery for Bone Engineering at Dental Implant Defects
Q. JIN1, C.A. DUNN1, M. TABA JR1, R.T. FRANCESCHI1, R.B. RUTHERFORD2, and W. GIANNOBILE1, 1 University of Michigan, Ann Arbor, USA, 2 Dentigenix, Seatle, WA, USA
2005
IADR
A challenge in the tissue engineering of alveolar bone surrounding oral or dental implants is achieving the targeted and sustained delivery of growth-promoting molecules at the osteotomy site. Bone morphogenetic protein-7 (BMP-7) has demonstrated the ability to stimulate bone regeneration in multiple skeletal sites including the craniofacial complex. Objective: This study evaluates in vivo gene delivery of BMP-7 for bone tissue engineering around titanium dental implants. Methods: The maxillary first molar teeth of 44 Sprague Dawley rats were extracted and allowed to heal for a period of one month. Large osteotomy defects were created in the edentulous ridge areas followed by the placement of dental implant fixtures. Recombinant adenoviral vectors encoding either BMP-7 or luciferase genes were delivered to the osseous defects using a collagen matrix. The kinetics of the gene expression was measured using in vivo bioluminescence optical imaging, while bone regeneration was evaluated under light and scanning electron microscopy. Results: The results revealed sustained, targeted transgene expression for up to 10 days at the osteotomy sites with nearly undetectable levels by 35 days. Treatment of dental implant fixtures with Ad/BMP-7 resulted in enhancement of alveolar bone defect fill, coronal new bone formation, and new bone to implant contact. Conclusion: In vivo gene therapy of BMP-7 offers potential for alveolar bone engineering applications. (This study is supported by NIDCR DE 13397, 15384, Delta Dental Fund and the American Academy of Implant Dentistry Foundation.)