The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism

Abstract

Vascularized composite allografts contain various tissue components and possess relative antigenicity, eliciting different degrees of alloimmune responses. To investigate the strategies for achieving facial allograft tolerance, we established a mouse hemiface transplant model, including the skin, muscle, mandible, mucosa, and vessels. However, the immunomodulatory effects of the mandible on facial allografts remain unclear. To understand the effects of the mandible on facial allograft survival, we compared the diversities of different facial allograft-elicited alloimmunity between a facial osteomyocutaneous allograft (OMC), including skin, muscle, oral mucosa, and vessels, and especially the mandible, and a myocutaneous allograft (MC) including the skin, muscle, oral mucosa, and vessels, but not the mandible. The different facial allografts of a BALB/c donor were transplanted into a heterotopic neck defect on fully major histocompatibility complex-mismatched C57BL/6 mice. The allogeneic OMC (Allo-OMC) group exhibited significant prolongation of facial allograft survival compared to the allogeneic MC group, both in the presence and absence of FK506 immunosuppressive drugs. With the use of FK506 monotherapy (2 mg/kg) for 21 days, the allo-OMC group, including the mandible, showed prolongation of facial allograft survival of up to 65 days, whereas the myocutaneous allograft, without the mandible, only survived for 34 days. The Allo-OMC group also displayed decreased lymphocyte infiltration into the facial allograft. Both groups showed similar percentages of B cells, T cells, natural killer cells, macrophages, and dendritic cells in the blood, spleen, and lymph nodes. However, a decrease in pro-inflammatory T helper 1 cells and an increase in anti-inflammatory regulatory T cells were observed in the blood and lymph nodes of the Allo-OMC group. Significantly increased percentages of donor immune cells were also observed in three lymphoid organs of the Allo-OMC group, suggesting mixed chimerism induction. These results indicated that the mandible has the potential to induce anti-inflammatory effects and mixed chimerism for prolonging facial allograft survival. The immunomodulatory understanding of the mandible could contribute to reducing the use of immunosuppressive regimens in clinical face allotransplantation including the mandible.

Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities

“…The loss of reinnervation results in the permanent loss of function of a limb; thus, promoting the improvement of the motor and sensory function of the transplanted limb through the recovery of peripheral nerves is paramount. Therefore, in VCA, nerve anastomosis needs to be performed in addition to vascular coaptation between the allografts and recipients, meaning that two challenges must be faced: allograft rejection [ 52 , 53 , 54 ] and nerve regeneration [ 3 ]. Encapsulated-tacrolimus hydrogel, with its two properties of inhibiting allograft rejection and promoting nerve regeneration, therefore holds promise for allogeneic limb transplantation.…”

Current global research on mandibular defect: A bibliometric analysis from 2001 to 2021

“…Wei Fu-chan of Chang Gung University in Taiwan mainly published clinical studies involving vascularized free flaps for mandibular defect repair ( Chang and Wei, 2021 ). This year, research has expanded to the mandibular allograft facial reconstruction field, which has a high academic influence ( Cardona et al, 2019 ; De Paz et al, 2021 ).…”

“…Traditional methods are becoming increasingly difficult to meet the requirements of precise mandibular reconstruction because of the 3D anatomical structure and complex function of the face. The latest research mentioned the use of biomaterials for mandibular defects, allogeneic transplantation of facial tissue, and drug-induced rapid distraction osteogenesis ( De Paz et al, 2021 ; Al Maruf et al, 2022 ; Shen et al, 2022 ), providing a new idea for the study of mandibular defects. In summary, combined with the bibliometric analysis, among the various methods of reconstruction in the field of mandibular defects, we consider that accurate mandibular reconstruction and tissue engineering bone regeneration technologies are research hotspots and frontiers in this field.…”