gms | German Medical Science

The first human face transplantation, performed in 2005, was considered as a major breakthrough in the treatment of severe disfigurement. In a decade, 40 similar procedures have then been performed worldwide, and led to unpreceded aesthetic and functional results in patients suffering from major disfiguring injuries. More or less extensive, the vascularized composite tissue allografts(VCA) were demonstrated to be able to sustain acute cellular rejection episodes, which could be prevented or treated by conventional immunosuppressive drugs, similar to those used in solid organ transplantation. Furthermore, the cortical reintegration of the face graft in the recipient’s body scheme was demonstrated to be successfully achieved through brain plasticity, if all motor and sensitive connections with cranial nerves had been restored at the time of surgery. However, long-term observations recorded on the earlier transplanted patients showed that their grafts developed chronic signs of humoral, vascular-targeted, rejection with, as a result, a limited lifetime of probably about 10 to 15 years. This observation raised the need to imagine new reconstructive options, aiming to overcome VCA natural limitations but also the general complications linked to the need of life-long immunosuppression. Therefore, we developed an original VCA-inspired strategy, applying the perfusion-decellularization/recellularization technology to composite tissue allografts. In order to study the feasibility of bioengineering the human face, this strategy was experimentally applied to elementary motor (lips, eyelids), non-motor (nose, auricle) and skeletal-based face subunits, first in large animal models, then on man. Decellularized non-immunogenic and biocompatible extracellular matrix (ECM) scaffolds of several facial subunits were so obtained, with a preserved and transplantable vascular tree. Furthermore, these scaffolds could be seeded by recipient’s stems cells, thereafter differentiating in various specialized tissue types, induced by native growth factors preserved in the donor ECM. At the end, this study was applied to the whole human face, as a final proof of concept, demonstrating that vascularized composite tissue engineering (VCE) might become in the future, the next step of progress in facial regenerative surgery, in between VCA and more advanced bioprinting technologies, which will rely on the same biological pathways.