Prefabrication of vascularised 3-D bone flaps with different growth factors in the great omentum in rabbits for reconstruction of large bony defects

Objectives: Reconstruction of bony defects can be done by free flaps. Donor site morbidity and misfit of the shape are limiting factors. The concept of using the patient as bioreactor solved many problems. The aim of the study was to evaluate if the great omentum is a capable anatomical site for prefabrication. Methods: In each of 30 adult male New Zealand white rabbits (4.0kg) 2 blocks of biomaterial were implanted in the great omentum with a central vascular pedicle in a cavity of the scaffold. The following five groups were created according to the biomaterial: (1) Bio-Oss® Block, (2) Bio-Oss® Block + rhBMP-2, (3) Bio-Oss® Block + rhBMP-2 + VEGF-165 (4) Bio-Oss® Block + autologous bone, (5) Bio-Oss® Block + autologous bone + rhBMP-2. CT examinations were performed after the implantation and 2, 4, 6 and 10 weeks later to define the bone density. The animals were sacrificed at 10 weeks postsurgery after intraperitoneal injection of fluorochromes and the specimens were collected for histological, immunohistochemical and histomorphometric analysis. Results: First analyses could show that the great omentum has advantage among other sites previously described with a long vascular pedicle, less postoperative functional impairment and more flexibility. The central blood vessel in the center of the scaffold resembles the natural anatomy of the mandible and other bones with a marrow cavity and enhances the ossification. The bone density increases particularly with the use of BMP-2 and VEGF-165 and has the highest values with additional use of autologous bone (HU: average between 483 (BioOss-Block alone) and 1054 (+ autologous bone with BMP-2). The floureszenz staining shows ossification also with BMP alone. Also the toluidine blue and HE staining shows ossifcation and development of new vessels in the scafold. There are indications that the efficacy of the dosage could be enhanced by addition of VEGF-165. Conclusions: We could demonstrate for the first time that the great omentum is a capable new anatomical site for prefabrication. It can be used as a bioreactor in vivo for prefabrication tissue-engineered bone. Prefabrication in the great omentum may go from bench to bedside and will show effectiveness in mandibular reconstruction. Palabras clave: prefabrication, omentum majus, reconstruction, bmp, vegf