4.7 Article

BMP gene delivery for alveolar bone engineering at dental implant defects

Journal

MOLECULAR THERAPY
Volume 11, Issue 2, Pages 294-299

Publisher

CELL PRESS
DOI: 10.1016/j.ymthe.2004.10.005

Keywords

gene therapy; osseclintegration; bone morphogenetic proteins; gene transfer; biornimetics; tissue engineering

Funding

  1. NCI NIH HHS [R24 CA083099, R24 CA83099] Funding Source: Medline
  2. NIAMS NIH HHS [P30 AR046024, P30-AR46024] Funding Source: Medline
  3. NIDCR NIH HHS [DE 13397, R01 DE013397-05, DE 13386, R01 DE013397, R01 DE013386] Funding Source: Medline

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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. This study evaluates in vivo gene delivery of BMP-7 for bone tissue engineering around titanium dental implants. The maxillary first molar teeth of 44 Sprague-Dawley rats were extracted and allowed to heal for a period of 1 month. Large osteotomy defects were created in the edentulous ridge areas followed by the placement of dental implant fixtures. Recombinant adenoviral vectors encoding either the BMP-7 or the luciferase gene were delivered to the osseous defects using a collagen matrix. The kinetics of the gene expression was measured using in vivo bloluminescence optical imaging, while bone regeneration was evaluated under light and scanning electron microscopy. 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. In vivo gene therapy of BIVIP-7 offers potential for alveolar bone engineering applications.

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