Topical delivery of immunosuppression to prolong xenogeneic and allogeneic split-thickness skin graft survival

Mastroianni, M. et al. (2018) Topical delivery of immunosuppression to prolong xenogeneic and allogeneic split-thickness skin graft survival. Journal of Burn Care and Research, 39(3), pp. 363-373. (doi: 10.1097/BCR.0000000000000597) (PMID:28639977) (PMCID:PMC5720930)

Abstract

Cadaveric skin allograft is the current standard of treatment for temporary coverage of large burn wounds. Porcine xenografts are viable alternatives but undergo α-1,3-galactose (Gal)–mediated hyperacute rejection and are lost by post-operative day (POD) 3 because of naturally occurring antibodies to Gal in primate recipients. Using baboons, we previously demonstrated that xenografts from GalT-KO swine (lacking Gal) provided wound coverage comparable with allografts with systemic immunosuppression. In this study, we investigate topical immunosuppression as an alternative to prolong xenograft survival. Full-thickness wounds in baboons were created and covered with xenogeneic and allogeneic split-thickness skin grafts (STSGs). Animals were treated with slow-release (TyroSphere-encapsulated) topical formulations (cyclosporine-A [CSA] or Tacrolimus) applied 1) directly to the STSGs only, or 2) additionally to the wound bed before STSG and 1). Topical CSA did not improve either xenograft or allograft survival (median: treated grafts = 12.5 days, control = 14 days; P = 0.27) with similar results when topical Tacrolimus was used. Pretreatment of wound beds resulted in a significant reduction of xenograft survival compared with controls (10 vs 14 days; P = 0.0002), with comparable results observed in allografts. This observation was associated with marked reduction of inflammation on histology with Tacrolimus and not CSA. Prolongation of allograft and xenograft survival after application to full-thickness wound beds was not achieved with the current formulation of topical immunosuppressants. Modulation of inflammation within the wound bed was effective with Tacrolimus pretreatment before STSG application and may serve as a treatment strategy in related fields.

• Item Type: Articles
• Additional Information: This work was supported by the Armed Forces Institute of Regenerative Medicine, Department of Defense, under Award No. W81XWH-08-2-0034. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702–5014 is the awarding and administering acquisition office. The authors also acknowledge funding from the National Institute of Health Grant No.1C 06 RR 20135-01 for production of the Miniature Swine breading facility.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Leonard, Dr David
• Authors: Mastroianni, M., Ng, Z. Y., Goyal, R., Mallard, C., Farkash, E. A., Leonard, D. A., Albritton, A., Shanmugarajah, K., Kurtz, J. M., Sachs, D. H., Macri, L. K., Kohn, J., and Cetrulo Jr., C. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Journal of Burn Care and Research
• Publisher: Oxford University Press
• ISSN: 1559-047X
• ISSN (Online): 1559-0488
• Published Online: 09 January 2018
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Journal of Burn Care and Research 39(3): 363-373
• Publisher Policy: Reproduced under a Creative Commons License