A tissue engineering approach to bone repair in large animal models and in clinical practice.

The repair of large segmental bone defects due to trauma, inflammation and tumor surgery remains a major clinical problem. Animal models were developed to test bone repair by tissue engineering approaches, mimicking real clinical situations. Studies differed with regard to animals (dog, sheep, goat), treated bone (femur, tibia, mandible), chemistry and structure of the scaffolds. Still, an advantage in the bone formation and in the healing of the segmental defect was always observed when scaffolds were seeded with bone marrow derived stromal cells (BMSCs). In the year 1998 was performed the first implantation of a porous ceramic construct in a bone segmental defect of a patient; it was the first construct seeded with cultured autologous osteogenic cells. Since then, only few other similar cases were treated by the same approach. However, in other fields, such as oral and maxillofacial surgery, injectable cells/platelet-rich plasma composites have been used as grafting materials for maxillary sinus floor augmentation and/or onlay plasty. More recently, the reconstruction of a human mandible was also reported by means of a bone-muscle-flap in vivo prefabrication technique, where the patient served as his own bioreactor. Indeed continuous implementations test and provide new means of defects treatment and cure. However, based on results so far obtained in animal models and pilot clinical studies, one can affirm that the bone tissue engineering approaches, although successful in most cases, need further validation before a wide application in clinics. In particular, the supply of oxygen and nutrients to the cells in the inner part of the implanted scaffolds remains a major concern, requiring additional investigations.