A Novel Orthotopic Vascularized Joint Allotransplant Model in the Rat: Applicability for Joint Transplantation with Short-Term Immunosuppression

Large joint defects present significant reconstructive challenges, and available reconstructive methods have important limitations. Transplantation of living allogenic joints would provide replacements closely matched to the dimensions and mechanical properties of resected tissues, combined with the desirable healing properties of vascularized autografts. Few such procedures have been performed clinically as they require long-term immunosuppression to maintain circulation and viability. Methods permitting vascularized joint allotransplantation without the health risks of immunosuppressive drugs or tolerance induction would be an important advance. The authors proposed a novel method by which this may be accomplished: microsurgical joint transfer with development of a new host-derived osseous blood supply by surgical neoangiogenesis. Immunosuppression needs only to allow sufficient time for neoangiogenesis to occur. They presented a new research model of vascularized joint allotransplantation.

Five vascularized rat knee joint allografts including the popliteal and bilateral femoral and iliac vessels, patella, extensor and flexor tendons, and an inferior epigastric-pedicled island skin flap were transplanted across a histocompatibility barrier. One animal served as a non-vascularized control by ligation of the pedicle and removal of the skin flap. Recipient-derived arteriovenous pedicles consisting of saphenous and inferior epigastric vessels with surrounding fascia were transversely passed through the tibial and femoral metaphyses of the allograft. Fixation was performed at the femur, tibia, and proximal fibula by intramedullary rods and intraosseous wires. All muscles were anatomically reattached. FK506 was given for 3 weeks postoperatively, after which a number of assessments were made. The pedicles' patency was tested and femoral and tibial cortical blood flow measured with the hydrogen washout method. Samples were perfused with Microfil and optically cleared for microangiography. Histologic evaluation of bone, cartilage, and synovium was performed.

In all animals, full passive range of motion was found and three animals regained full and outwardly normal use of their hind limb (60%). One skin flap was necrotic after one day and the corresponding pedicle was thrombosed at sacrifice (25%). One arteriovenous pedicle was thrombosed (10%). Measurable flow was obtained in those bones where the pedicle had remained patent through the survival period. Implanted arteriovenous pedicles produced new vascular networks on angiography. No rejection was seen, and necrosis was found only in the control and early pedicle thrombosis cases.

Full functional recovery, surgical neoangiogenesis, and pedicle monitoring make this an ideal model to study the application of living joint allotransplantation with the aim of short-term immunosuppression.