Repair of orbital wall defects using biocoral scaffolds combined with bone marrow stem cells enhanced by human bone morphogenetic protein-2 in a canine model

Abstract

Repair of orbital bone defects caused by trauma, infection or cancer is a continuous challenge in reconstructive surgery. Few studies have reported the application of tissue engineering for the repair of orbital bone defects in large animal models. Thus, we investigated the effects of tissue-engineered bone enhanced by the human bone morphogenetic protein-2 (BMP2) on the repair of orbital wall defects in a canine model. Autologous bone marrow stromal cells (BMSCs) from 16 Beagle dogs were isolated and cultured in vitro. Passage 2 cells were transfected with adenovirus containing human BMP2 (adv-BMP2) and tissue-engineered bone was constructed using BMP2-expressing BMSCs seeded on a biocoral scaffold. Circular defects (12-mm diameter) created bilaterally in the canine medial orbital wall, were treated with one of the following: adv-BMP2-transfected BMSC/coral composite (group I, n=8), BMSC/coral composite (group II, n=8), biocoral alone (group III, n=8), or were left untreated (group IV, n=8). Four samples from each group were harvested at 12 and 24 weeks after surgery, and the volume and density of newly regenerated bone were determined by micro-computed tomographic (micro-CT) measurement. The rate of new bone deposition and regeneration was measured by tetracycline/calcein labeling and histomorphometric analysis. The results showed that a canine 12-mm circular orbital defect was a critical-sized defect, and the micro-CT and histomorphometry detection results indicated that the combined delivery of BMSCs and BMP2 (group I) resulted in the highest regenerative effects on orbital bone defects, compared to the other groups without BMP2. Biocoral scaffolds combined with BMSCs enhanced by BMP2 could improve the healing of critical-sized medial orbital wall defects in canines.