Maxillary sinus elevation with BMP-2 gene enhanced tissue-engineered bone

Objectives: To study the effects of maxillary sinus floor elevation by a tissue-engineered bone complex with beta-tricalcium phosphate (b-TCP) and bone morphogenetic protein-2 (BMP-2) gene-modified bone marrow stromal cells (bMSCs) in rabbits.

Methods: bMSCs derived from New Zealand rabbit bone marrow were cultured and transduced with the AdBMP-2, AdEGFP gene in vitro. These gene-modified autologous bMSCs were then combined with a b-TCP granule scaffold at a concentration of 20 x 10⁶ cells/mL and used to elevate the maxillary sinus floor in rabbits (with volume of about 15 x 5 x 3 mm). Twenty rabbits were randomly allocated into groups and killed at weeks 2 and 8. For each timepoint, we made 20 maxillary sinus floor elevation surgeries bilaterally in 10 rabbits for the following groups (n = 5 per group): Group A (AdBMP-2-bMSCs/b-TCP), group B (AdEGFP-bMSCs/b-TCP), Group C (untransduced bMSCs/b-TCP), and group D (b-TCP alone). All samples were evaluated by histology, immunohistochemistry, and histomorphometric analysis.

Results: BMP-2 transcription and expression were clearly detected with 50 pfu/cell AdBMP-2 transduction by RT-PCR and Western blot analysis in vitro. The augmented maxillary sinus space was maintained for the four groups 8 wks post-surgery, while new bone area increased significantly over time. At each timepoint, bone areas in groups A, B, and C were significant larger than that in group D (p < 0.05, ANOVA), while group A was the largest among the groups. In the BMP-2 group, lamellar bone structure with fatty marrow tissue was clearly detected in the center of the elevated space at week 8. Accordingly, immunohistochemistry results revealed more intensive Osteocalcin (OC) and VEGF expression in this group. Strong EGFP detected in newly formed bone in group B suggested that the source of newly formed bone was bMSCs.

Conclusion: AdBMP-2 gene-enhanced bMSCs can effectively promote new bone formation and maturation. The above results suggest that BMP-2 gene-enhanced tissue-engineered bone could be a novel alternative for dental implant-associated maxillary sinus elevation.