Optimization of Ex Vivo Machine Perfusion and Transplantation of Vascularized Composite Allografts

Laura C. Burlage, Alexandre G. Lellouch, Corentin B. Taveau, Philipp Tratnig-Frankl, Casie A. Pendexter, Mark A. Randolph, Robert J. Porte, Laurent A. Lantieri, Shannon N. Tessier, Curtis L. Cetrulo, Korkut Uygun

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background: Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a protocol for ex vivo subnormothermic oxygenated machine perfusion (SNMP) on rodent hindlimbs and to validate our protocol in a heterotopic hindlimb transplant model. Methods: In this optimization study we compared three different solutions during 6 h of SNMP (n = 4 per group). Ten control limbs were stored in a preservation solution on Static Cold Storage [SCS]). During SNMP we monitored arterial flowrate, lactate levels, and edema. After SNMP, muscle biopsies were taken for histology examination, and energy charge analysis. We validated the best perfusion protocol in a heterotopic limb transplantation model with 30-d follow up (n = 13). As controls, we transplanted untreated limbs (n = 5) and hindlimbs preserved with either 6 or 24 h of SCS (n = 4 and n = 5). Results: During SNMP, arterial outflow increased, and lactate clearance decreased in all groups. Total edema was significantly lower in the HBOC-201 group compared to the BSA group (P = 0.005), 4.9 (4.3-6.1) versus 48.8 (39.1-53.2) percentage, but not to the BSA + PEG group (P = 0.19). Energy charge levels of SCS controls decreased 4-fold compared to limbs perfused with acellular oxygen carrier HBOC-201, 0.10 (0.07-0.17) versus 0.46 (0.42-0.49) respectively (P = 0.002). Conclusions: Six hours ex vivo SNMP of rodent hindlimbs using an acellular oxygen carrier HBOC-201 results in superior tissue preservation compared to conventional SCS.

Original languageEnglish (US)
Pages (from-to)151-161
Number of pages11
JournalJournal of Surgical Research
Volume270
DOIs
StatePublished - Feb 2022

Bibliographical note

Funding Information:
Study design: K.U., C.L.C., S.N.T., M.A.P., A.G.L. and L.C.B. Performed study: L.C.B., C.A.P., C.B.T., P.T.F and A.G.L. Collected data: L.C.B., C.A.P., C.B.T, P.T.F and A.G.L. Analyzed data: L.C.B., A.G.L. and K.U. Scientific review and direction: R.J.P., L.A.L., K.U., C.L.C., S.N.T., A.G.L. and L.C.B. Manuscript preparation and corrections: all authors. Study category: Transplantation and/or Immunology. Study type: Experimental animal studies; species rodent. This material is partially based upon work supported by the National Science Foundation under Grant No. EEC 1941543.

Funding Information:
Funding from the U.S. National Institutes of Health (grants R44AI124835 and R44AI145782 in collaboration with Sylvatica Biotech Inc, and R01EB028782) and the Shriners Hospitals for Children (86200-BOS) is gratefully acknowledged. We thank the Shriners Boston Mass Spectrometry Core, and Morphology and Imaging Core for access to equipment and expertise.

Funding Information:
The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding, and administering acquisition office. This work was supported by the Office of Assistant Secretary of Defense for Health Affairs, through the Reconstructive Transplant Research Program, Technology Development Award under Award Nos. W81XWH1710680, and W81XWH1910440.

Funding Information:
The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding, and administering acquisition office. This work was supported by the Office of Assistant Secretary of Defense for Health Affairs, through the Reconstructive Transplant Research Program, Technology Development Award under Award Nos. W81XWH1710680 and W81XWH1910440.

Publisher Copyright:
© 2021

Keywords

  • energy charge
  • face transplantation
  • free flap
  • limb transplantation
  • oxygen carrier
  • oxygenated machine perfusion
  • plastic surgery
  • preservation
  • vascularized composite allotransplantation

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

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