Periosteum-guided prefabrication of vascularized bone of clinical shape and volume

Background: Large craniofacial skeletal defects require complex reconstruction. Vascularized tissue transfer is the current standard in treatment, but these operations are technically difficult and associated with donor-site morbidity. Guided flap prefabrication offers a technique for endogenously engineering vascularized composite tissues with complex three-dimensional structure. This study evaluates the relationship between implantation time and tissue structure for generating tissues of clinically relevant volume and structure. Methods: Twenty skeletally mature domestic sheep were implanted with poly(methyl methacrylate) chambers designed to mimic the size and shape of the mental protuberance of the mandible. Each chamber was filled with morcellized bone graft and implanted with the open face apposed to the cambium layer of the rib periosteum. Chambers were harvested at 3, 6, 9, 12, and 24 weeks, and the tissue inside the chambers was analyzed for shape conformation to chamber geometry, gross tissue volume, and bone histomorphometric parameters. Results: Histologically, active endochondral, direct, and appositional bone formation was observed. Calcified tissue area and new bone formation increased for each time point up to 12 weeks of implantation. The tissues formed maintained volumetric and geometrical structure consistent with the chamber up to 9 weeks after implantation. Significant decreases in total volume and agreement with chamber geometry were observed at 12 and 24 weeks. Conclusions: Periosteum-guided tissue prefabrication was found to be an effective means of engineering three-dimensional vascularized bone of clinical size and shape. The optimal duration of incubation before significant volume loss occurs is 9 weeks in this large-animal model.