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.
Highlights
Most reconstructive procedures for major tissue defects such as trauma, tumor excision, or congenital anomalies can be performed with autologous tissue
The placement of the transplanted hemiface on the neck can reduce the risk of autonomy (mice placement of the transplanted hemiface on the neck can reduce the risk of autonomy flap)and andincrease increasesurgery surgerysuccess
To further understand thethe effects of the mandible on on facial alfor vessel anastomosis effects of the mandible facial lograft survival, we removed the mandible from a whole hemiface subunit, including the allograft survival, we removed the mandible from a whole hemiface subunit, including skin, muscle, mandible, teeth, oraloral mucosa, andand vessels, in the group, compared to the the skin, muscle, mandible, teeth, mucosa, vessels, in the group, compared to group with the whole hemiface
Summary
Most reconstructive procedures for major tissue defects such as trauma, tumor excision, or congenital anomalies can be performed with autologous tissue. The treatment of orofacial anomalies such as orofaciodigital syndrome, which is a group of hereditary diseases characterized by deformities of the face, mouth, feet, and hands, involves careful periodic follow-up and a multidisciplinary approach [4]. Other orofacial anomalies, such as temporomandibular diseases, including multifactorial musculoskeletal diseases related to masticatory muscles, the temporomandibular joint, and accessory structures, can be treated by physiotherapy such as massage techniques [5,6] or by polyphenols like curcumin, resveratrol, and epigallocatechin3-gallate [7]. If the need for lifelong immunosuppressive drugs could be obviated or decreased, VCA could be more widely used
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