The gracilis myocutaneous free flap in swine: an advantageous preclinical model for vascularized composite allograft transplantation research.

Vascularized composite allotransplantation (VCA) has become a clinical reality, prompting research aimed at improving the risk-benefit ratio of such transplants. Here, we report our experience with a gracilis myocutaneous free flap in Massachusetts General Hospital miniature swine as a preclinical VCA model. Fourteen animals underwent free transfer of a gracilis myocutaneous flap comprised of the gracilis muscle and overlying skin, each tissue supplied by independent branches of the femoral vessels. End-to-end anastomoses were performed to the common carotid artery and internal jugular vein, or to the femoral vessels of the recipients. Thirteen of fourteen flaps were successful. A single flap was lost due to compromise of venous outflow. This model allows transplantation of a substantial volume of skin, subcutaneous tissue, and muscle. The anatomy is reliable and easily identified and harvest incurs minimal donor morbidity. We find this gracilis myocutaneous flap an excellent pre-clinical model for the study of vascularized composite allotransplantation.

Leto Barone AA ，Leonard DA ，Torabi R ，Mallard C ，Glor T ，Scalea JR ，Randolph MA ，Sachs DH ，Cetrulo CL Jr ... -  《-》

Facial subunit composite tissue allografts in nonhuman primates: I. Technical and immunosuppressive requirements for prolonged graft survival.

Barth RN ，Bluebond-Langner R ，Nam A ，Stanwix M ，Shipley S ，Bartlett ST ，Rodriguez ED ... -  《-》

Heterotopic Transplantation of Allogeneic Vertical Rectus Abdominis Myocutaneous Flaps in Miniature Swine.

Vascularized composite tissue allotransplantation (VCA) opens new possibilities for reconstruction of complex tissue defects, including upper extremity and facial transplantation. The main challenges in VCA transplantation are the side effects of long-term immunosuppression and chronic graft rejection. Translational preclinical animal models are crucial for VCA research to improve clinical outcomes and to study underlying immunologic mechanisms. Herein, we describe a novel, large animal, non-bone-bearing VCA model in inbred, swine leukocyte antigen-typed miniature swine. Transplantation of vertical rectus abdominis myocutaneous (VRAM) flaps was performed between fully swine leukocyte antigen-mismatched miniature swine. The flaps were transferred to the posterolateral aspect of the neck of recipients and anastomosed to the common carotid artery and internal jugular vein. Different immunosuppressive drug regimens were used. Clinical graft evaluation was performed daily, and punch biopsies were taken for histology. Ten VRAM transplants were performed. The mean ischemia time was 89.4 min (SD ± 47), mean pedicle length 7.5 cm (SD ± 2), mean venous diameter 2.5 mm (SD ± 0.4), and mean arterial diameter 2.2 mm (SD ± 0.3). Follow-up demonstrated good correlation between clinical appearance and progression of graft rejection confirmed by histologic assessment. Complications were intraoperative cardiac arrest in one recipient and one flap loss due to venous compromise. VRAM transplantation in miniature swine is an appropriate preclinical VCA model, with the advantage of good clinical and histologic correlation during the course of rejection, as well as easy access to the graft. The availability of inbred, haplotyped animals allows studies across different major histocompatibility complex barriers in a non-bone-bearing VCA.

Waldner M ，Elgendy TY ，Kim DY ，Öksüz S ，Schweizer R ，Zhang W ，Minervini MI ，Komatsu C ，Plock JA ，Gorantla VS ，Washington KM ，Thomson AW ，Solari MG ... -  《-》

Microvascular porcine model for the optimization of vascularized composite tissue transplantation.

Devastating extremity injuries are prevalent but most often survivable on the modern battlefield. The complexity of these injuries requires advanced methods of reconstruction. This study is designed to validate the feasibility of gracilis myocutaneous flap transplantation via microvascular free tissue transfer in a porcine model. This model will facilitate study of autotransplant physiology as well as vascularized composite allotransplantation as an evolving method for reconstructing previously nonreconstructable injuries. A donor gracilis myocutaneous flap is procured from Yorkshire swine. The right external carotid artery and internal jugular vein are prepared as the recipient axis for microvascular anastomoses. Group 1 undergoes immediate microvascular anastomosis with resultant 1-h ischemic period. Group 2 undergoes delayed anastomosis with 3-h ischemic period. Markers of ischemia-reperfusion injury are evaluated after anastomosis and on postoperative days 1, 2, 7, and 14. A novel porcine model for microvascular composite tissue transplantation is demonstrated. Ischemia period-dependent elevations in circulating biomarkers (lactate dehydrogenase [LDH], creatine kinase [CK], and aspartate transaminase [AST]) demonstrate the effects of prolonged ischemia. Both groups showed marked LDH elevation without significant statistical intergroup difference (P=0.250). The difference in CK and AST levels at 24h showed strong significance (P<0.0001). A novel method of vascularized gracilis myocutaneous flap transplantation was validated in the Yorkshire swine. Assays for skeletal muscle tissue injury (LDH, CK, and AST) showed ischemia period-dependent response providing assessment of ischemia-reperfusion injury at the cellular level. Subsequent studies will evaluate agents that mitigate ischemia-reperfusion injury and transition these findings to potentiate vascularized composite allotransplantation.

Villamaria CY ，Rasmussen TE ，Spencer JR ，Patel S ，Davis MR ... -  《-》

Porcine heterotopic composite tissue allograft transplantation using a large animal model for preclinical studies.

Kuo YR ，Sacks JM ，Lee WP ，Wu WS ，Kueh NS ，Yao SF ，Chiang YC ... -  《-》