Ex Vivo Bone Morphogenetic Protein‐2 Gene Delivery Using Bone Marrow Stem Cells in Rabbit Maxillary Sinus Augmentation in Conjunction With Implant Placement

Abstract

This study evaluates the potential of bone morphogenetic protein 2 (BMP-2) gene-transduced bone marrow stem cells (BMSCs) to facilitate osseous healing after rabbit maxillary sinus augmentation in conjunction with implant placement. Autologous BMSCs derived from New Zealand white rabbits were cultured and transduced with BMP-2 using an adenovirus vector. Transduced BMSCs (BMP-2/BMSCs) were then combined with a deproteinized bovine bone mineral (DBBM) scaffold. Twenty-seven animals were randomly allocated into three groups: 1) control, sinus grafted with DBBM alone; 2) BMSC, sinus grafted with non-transduced BMSCs and DBBM; and 3) BMP-2/BMSC, sinus grafted with BMP-2/BMSCs and DBBM. During these procedures, a mini-implant was placed in the floor of the sinus. Animals were sacrificed at 2, 4, and 8 weeks after surgery. New bone area and bone-to-implant contact (BIC) were evaluated histomorphometrically. At 2 and 4 weeks, the BMP-2/BMSC group showed more new bone area and higher BIC than the other two groups. BMP-2/BMSCs were detected with confocal microscopy for up to 4 weeks, which indicates that transduced cells contributed to new bone formation. However, at 8 weeks, there was no difference in new bone area or BIC among the three groups. These results suggest that BMP-2 delivery using BMSCs may result in earlier and increased bone formation in the maxillary sinus. This finding may offer more stable bone support to implants and reduce healing times. However, this study also revealed limitations in the stimulatory effect of BMP-2/BMSCs, such as diminished activity over time in later healing stages.