Lymph Node Inclusion in a Modified Osteomyocutaneous Allograft for Vascularized Composite Allotransplantation: Establishment and Feasibility Assessment in a Pig Model.

Abstract

Background Representative translational animal models play a key role in vascularized composite allotransplantation (VCA) research. A composite porcine hindlimb flap, previously described, is a relevant preclinical model. However, its bulkiness and the absence of critical immunologic tissues make it less suitable for investigating the unique immunologic features of VCA. We aimed to further develop this model by reducing its bulkiness and by including donor-draining lymph nodes.Methods We conducted an anatomic study by harvesting 11 porcine osteomyocutaneous flaps (4 conventional and 7 modified techniques), which were characterized by computed tomography. Furthermore, 8 allotransplantations were performed in Swiss landrace pigs. After the procedure, animals were assigned to a model development and control group (N = 4 per group). No immunosuppression was given, and animals were followed up until grade 3 rejection.Results With the modified technique, the flap weight was significantly reduced with a mean weight of 831 g, corresponding to 1.8% total body weight versus 1710 g in the conventional technique, representing 4.2% of total body weight (P < 0.0001). The muscle/bone ratio was reduced from 8.24 (conventional) to 2.92 (modified), (P = 0.03). Histologically, graft-draining lymph nodes showed typical changes related to rejection and no signs of ischemia after in vivo transplantation.Conclusions By modifying the surgical technique, the bulkiness of the flap was markedly reduced, without impairing its vascularization and reliably including vascularized graft-draining lymph nodes. Our modified VCA model in the pig presents distinct advantages for surgery as well as immunologic analysis, warranting a large-scale use for experimental reconstructive transplantation studies.