Skin and soft tissue-containing VCA models include allografts containing skin, subcutaneous tissue, fat and muscle (Fig. 19.1). The most frequently used skin/soft tissue VCA model is the groin flap, which is also one of the first models used in VCA research [7]. This model contains skin, fat and lymphoid tissue harvested on superficial epigastric vessels or femoral vessels. The groin flap is preferred for immunologic studies as it is technically simple and transplantation procedures have low mortality rates. The main disadvantage of this model is the small size of the skin paddle. Later, various VCA models including, skin, subcutaneous tissue and different muscles (such as semimembranosus and pectoralis) were described [8, 9]. Another soft tissue model is the total abdominal wall transplantation model in which the entire abdominal wall skin is harvested on bilateral femoral vessels to investigate the effect of skin amounts on chimerism [10].

The first rat hindlimb allotransplantation model was described in 1978 [3]. In this model, a circumferential skin incision at the mid-thigh level is made and femoral vessels, saphenous nerve, sciatic nerve and femoral nerve are dissected and thigh muscles are sharply cut. Next, the femoral bone is cut with a saw. The recipient is prepared using the same technique and the donor hindlimb is transferred to the recipient. Following the fixation of the femoral bone with an intramedullary rod and wire suture, femoral vessels are subsequently anastomosed and the femoral, sciatic and saphenous nerves are coaptated. Muscles and skin are closed anatomically. This transplantation is a complex procedure and quite similar to human hand transplantation. However, it is time consuming, requires expertise and has a high mortality rate. Thus, simpler models are needed to obtain good survival of the recipient animal and robust statistics. Later, Chang et al. described transplantation of the groin-thigh osteomyocutaneous flap, which is composed of skin (groin), muscle (thigh), and bone (two-thirds of the femur), based on the femoral vessels and superficial epigastric vessels [11]. The advantages of this model are shortened operative time, easy monitoring of graft rejection and decreased mortality rates.

Immunomodulatory VCA models include immunologic tissues such as bone marrow and thymus, to increase chimerism and induce immunotolerance (Fig. 19.2). Generally, the most frequently used tissue for immunomodulation is bone marrow, especially femoral bone marrow. Tai et al. described a vascularized femur transplant comprising femoral bone, bone marrow, periosteum, cartilage and muscle tissues [12]. This model was used to investigate the effects of vascularized bone marrow transplantation on chimerism induction. Later, a bilateral, vascularized femoral bone transplantation model was described by Agaoglu and Siemionow [13]. This model included the same tissue types, but with a higher bone marrow content, which induced higher levels of donor-specific chimerism. Another immunomodulatory model is the composite vascularized skin/bone allograft model, which is basically a combination of the groin flap model with vascularized femur transplantation [14]. The skin component helps to follow-up the rejection and bone marrow is used to induce chimerism. The osteomyocutaneous iliac flap is composed of iliac bone, abdominal wall musculature, and a wide skin island, harvested on iliolumbar artery and vein [15]. The sternum is also used as a bone marrow source in VCA studies. The sternum, including presternal skin and muscles, was first transplanted by Santiago et al. [16]. The allograft was harvested on the thoracic aorta and superior vena cava.

When the amount of bone marrow cells is compared, it is seen that the limb model contains 48.75 × 10⁶ bone marrow cells. On the other hand, iliac, femur, and sternum models contain 25, 50, and 7.5 × 10⁶ bone marrow cells, respectively.

Another method of tolerance induction in experimental studies is to include thymus tissue. The first thymus transplantation was described by Jiang et al. in 1999 [17]. Later, composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation models were developed [18].

The face has different anatomic units and structures. Thus, there are many facial VCA models based on the transplantation of these structures (Fig. 19.3). Siemionow et al. were the first to develop a full-face scalp allotransplantation model [4

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