To test the hypothesis that the use of rhBMP2 in established defects requires additional growth factors such as rhVEGF to accomplish effective bone repair. Horizontal/vertical defects of 2cm length and 1cm height were created bilaterally in the alveolar crest of the maxillae of 18 minipigs together with the extraction of all premolar teeth and one molar tooth on both sides. After 3months of healing, defects were augmented with 0.5g particulate PDLLA/CaCO3 composite loaded with 400µg rhBMP2/50µg rhVEGF165 on one side and 800µg rhBMP2 on the other in 12 test animals, whereas defects in six control animals were sham operated and left unfilled on one side and augmented with blank carriers on the other. After 4 and 13weeks, the animals were evaluated each for area of new bone formation (mm²) and bone density (area %). Augmentations with carriers loaded with 800g µrhBMP2 failed to induce significantly more bone than in the augmentations with unloaded carrier after 4 and 13weeks (p=.1000, p=.381). Augmentations with carriers loaded with 400µg rhBMP2 and 50µg erhVEGF165 resulted in significantly increased bone formation after 13weeks (p=.024) compared to blank carriers. Soft tissue in augmentations with combined rhBMP2/rhVEGF165 loading exhibited numerous microvessels compared to soft tissue in augmentations with rhBMP2. It is concluded that effective bone regeneration in augmentations of established alveolar ridge defects may require the application of rhVEGF additionally to rhBMP2.
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