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The Journal of Bone and Joint Surgery (American) 86:281-289 (2004)
© 2004 The Journal of Bone and Joint Surgery, Inc.

Survival of Microvascular Physeal Allograft Transplants Following Withdrawal of Short-Term Postoperative Immunosuppression

Peter W. Bray, MD, MSc, FRCS(C)1, Peter C. Neligan, MB, FRCS(I), FRCS(C)1, C. Vaughan A. Bowen, MD, MB, CHB, FRCS(C)1 and Martin I. Boyer, MD, MSc, FRCS(C)2

1 Division of Surgical Research, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada
2 Department of Orthopaedic Surgery, Barnes-Jewish Hospital at Washington University, One Barnes-Jewish Hospital Plaza, Suite 11300, West Pavilion, Saint Louis, MO 63110. E-mail address for M.I. Boyer: boyerm{at}msnotes.wustl.edu

Investigation performed at the Division of Surgical Research, The Hospital for Sick Children, Toronto, Ontario, Canada

In support of their research or preparation of this manuscript, one or more of the authors (C.V.A.B.) received grants or outside funding from Medical Research Council of Canada (Operating Grant MA-10882). None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: Physeal necrosis following vascularized allograft transplantation occurs because of vascular rejection. The effect of immunosuppression withdrawal on physeal viability after bone-healing to the recipient site was investigated with use of a validated model for heterotopic microvascular transplantation of rabbit tibial physeal allografts. Our hypothesis was that an allograft survives after withdrawal of immunosuppression only if bone-healing, and therefore epiphyseal and metaphyseal vascular continuity, occurs between the transplanted physis and the recipient bone.

Methods: Physeal grafts with adjacent exposed epiphyseal and metaphyseal bone were transplanted to allogeneic recipients. Graft circulation was restored microsurgically. The immunosuppression regimen consisted of cyclosporine, administered for six weeks, followed by withdrawal of immunosuppression for four weeks. The animals were killed at ten weeks postoperatively. Group I consisted of twelve allografts that were transferred with bone contact between the transplanted graft and the iliac crest recipient site, whereas group II consisted of twelve allografts transplanted without bone contact. Control groups had identical surgical procedures without immunosuppression. Longitudinal growth was assessed by fine-detail radiography, and osseous union was evaluated histologically. Transplanted physes were evaluated histologically, and cellular viability was quantified by bromodeoxyuridine uptake. Two-way analysis of variance was used to compare physeal viability between groups.

Results: Following immunosuppression withdrawal, the physeal grafts with bone contact had significantly greater viability indices (16.0 ± 2.9 compared with 0.0 ± 0.0, p < 0.005) and decreased longitudinal growth (5.1 ± 1.9 mm compared with 10.3 ± 3.5 mm, p < 0.05), and they demonstrated histological features that were consistent with continued viability associated with mild rejection compared with grafts transplanted without bone contact. Abnormalities of physeal architecture, however, were seen routinely. All control physes transferred without immunosuppression were nonviable and did not grow.

Conclusions: The viability of physeal allograft transplants is preserved following the withdrawal of immunosuppression, provided that the graft design and recipient site preparation allow for epiphyseal and metaphyseal neovascularization mediated by bone-healing between graft and recipient.

Clinical Relevance: Short-term use of systemic immunosuppression might prove to be acceptable ethically and useful clinically following vascularized physeal allotransplantation if continued viability and longitudinal growth of the physis could be ensured.


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