Craniomaxillofacial reconstruction using allotransplantation and tissue engineering: Challenges, opportunities, and potential synergy

The face is composed of an intricate underlying bony/cartilaginous framework that supports muscle, secretory organs, and sophisticated skin/subcutaneous structures. These components are attached through numerous ligaments and interact dynamically with a vast neurovascular network. The most sophisticated autologous reconstructive techniques, utilizing composite free-tissue flaps, are often inadequate to restore extensive maxillofacial defects. Massive craniomaxillofacial (CMF) defects resulting from trauma, oncologic resection, or congenital deformity present a unique challenge to reconstructive surgeons. Therefore, recent advances in craniofacial surgery and immunotherapy spurred the innovation of composite tissue allotransplantation (CTA), which permits reconstruction with tissue composed of all necessary components. However, CMF allotransplantation carries with it side effects of lifelong immunosuppression. Furthermore, the donor skeletal framework may not provide an ideal match, resulting in less than ideal occlusion and soft-tissue anthropometrics. An alternative to transplantation, tissue engineering, has provided hope for regenerating missing tissue and avoiding the need for immunosuppression. Many tissue subtypes, including bone and cartilage, have been successfully created, with sparse reports of clinical application. Tissue-engineered composite tissue required for complete CMF reconstruction continues to elude development, with vascular supply and tissue interactions posing the largest remaining obstacles. We report herein the current status and limitations of CTA and tissue engineering. Furthermore, we describe for the first time our vision of hybridization of CTA and engineering, utilizing the strengths of each strategy.