Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol

Casie A. Pendexter; Omar Haque; Mohammadreza Mojoudi; Sarah Maggipinto; Marion Goutard; Simona Baicu; Alexandre G. Lellouch; James F. Markmann; Gerald Brandacher; Heidi Yeh; Shannon N. Tessier; Curtis Cetrulo; Korkut Uygun

doi:10.1371/journal.pone.0266207

Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol

Casie A. Pendexter, Omar Haque, Mohammadreza Mojoudi, Sarah Maggipinto, Marion Goutard, Simona Baicu, Alexandre G. Lellouch, James F. Markmann, Gerald Brandacher, Heidi Yeh, Shannon N. Tessier, Curtis Cetrulo, Korkut Uygun

Advanced Technologies for Preservation of Biological Systems

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7 Scopus citations

Abstract

Vascularized composite allografts (VCAs) refer to en bloc heterogenous tissue that is transplanted to restore form and function after amputation or tissue loss. Rat limb VCA has emerged as a robust translational model to study the pathophysiology of these transplants. However, these models have predominately focused on hindlimb VCAs which does not translate anatomically to upper extremity transplantation, whereas the majority of clinical VCAs are upper extremity and hand transplants. This work details our optimization of rat forelimb VCA procurement and sub-normothermic machine perfusion (SNMP) protocols, with results in comparison to hindlimb perfusion with the same perfusion modality. Results indicate that compared to hindlimbs, rat forelimbs on machine perfusion mandate lower flow rates and higher acceptable maximum pressures. Additionally, low-flow forelimbs have less cellular damage than high-flow forelimbs based on oxygen uptake, edema, potassium levels, and histology through 2 hours of machine perfusion. These results are expected to inform future upper extremity VCA preservation studies.

Original language	English (US)
Article number	e0266207
Journal	PloS one
Volume	18
Issue number	1 January
DOIs	https://doi.org/10.1371/journal.pone.0266207
State	Published - Jan 2023

Bibliographical note

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 No. W81XWH-17-1-0680. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. This material is partially based upon work supported by the National Science Foundation under Grant No. EEC 1941543. Funding from the US National Institutes of Health (R44AI124835, R01EB028782) is gratefully acknowledged. We thank the Shriners Boston Morphology and Imaging Core, Genomics and Proteomics Core, Mass Spectrometry Core and the Translational Regenerative Medicine Special Shared Facility for access to equipment and expertise. We also thank Florence Lin Min for the ATP and EC analysis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2023 Pendexter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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

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title = "Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol",

abstract = "Vascularized composite allografts (VCAs) refer to en bloc heterogenous tissue that is transplanted to restore form and function after amputation or tissue loss. Rat limb VCA has emerged as a robust translational model to study the pathophysiology of these transplants. However, these models have predominately focused on hindlimb VCAs which does not translate anatomically to upper extremity transplantation, whereas the majority of clinical VCAs are upper extremity and hand transplants. This work details our optimization of rat forelimb VCA procurement and sub-normothermic machine perfusion (SNMP) protocols, with results in comparison to hindlimb perfusion with the same perfusion modality. Results indicate that compared to hindlimbs, rat forelimbs on machine perfusion mandate lower flow rates and higher acceptable maximum pressures. Additionally, low-flow forelimbs have less cellular damage than high-flow forelimbs based on oxygen uptake, edema, potassium levels, and histology through 2 hours of machine perfusion. These results are expected to inform future upper extremity VCA preservation studies.",

author = "Pendexter, {Casie A.} and Omar Haque and Mohammadreza Mojoudi and Sarah Maggipinto and Marion Goutard and Simona Baicu and Lellouch, {Alexandre G.} and Markmann, {James F.} and Gerald Brandacher and Heidi Yeh and Tessier, {Shannon N.} and Curtis Cetrulo and Korkut Uygun",

note = "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 No. W81XWH-17-1-0680. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. This material is partially based upon work supported by the National Science Foundation under Grant No. EEC 1941543. Funding from the US National Institutes of Health (R44AI124835, R01EB028782) is gratefully acknowledged. We thank the Shriners Boston Morphology and Imaging Core, Genomics and Proteomics Core, Mass Spectrometry Core and the Translational Regenerative Medicine Special Shared Facility for access to equipment and expertise. We also thank Florence Lin Min for the ATP and EC analysis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2023 Pendexter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

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AU - Pendexter, Casie A.

AU - Haque, Omar

AU - Mojoudi, Mohammadreza

AU - Maggipinto, Sarah

AU - Goutard, Marion

AU - Baicu, Simona

AU - Lellouch, Alexandre G.

AU - Markmann, James F.

AU - Brandacher, Gerald

AU - Yeh, Heidi

AU - Tessier, Shannon N.

AU - Cetrulo, Curtis

AU - Uygun, Korkut

N1 - 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 No. W81XWH-17-1-0680. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. This material is partially based upon work supported by the National Science Foundation under Grant No. EEC 1941543. Funding from the US National Institutes of Health (R44AI124835, R01EB028782) is gratefully acknowledged. We thank the Shriners Boston Morphology and Imaging Core, Genomics and Proteomics Core, Mass Spectrometry Core and the Translational Regenerative Medicine Special Shared Facility for access to equipment and expertise. We also thank Florence Lin Min for the ATP and EC analysis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2023 Pendexter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2023/1

Y1 - 2023/1

N2 - Vascularized composite allografts (VCAs) refer to en bloc heterogenous tissue that is transplanted to restore form and function after amputation or tissue loss. Rat limb VCA has emerged as a robust translational model to study the pathophysiology of these transplants. However, these models have predominately focused on hindlimb VCAs which does not translate anatomically to upper extremity transplantation, whereas the majority of clinical VCAs are upper extremity and hand transplants. This work details our optimization of rat forelimb VCA procurement and sub-normothermic machine perfusion (SNMP) protocols, with results in comparison to hindlimb perfusion with the same perfusion modality. Results indicate that compared to hindlimbs, rat forelimbs on machine perfusion mandate lower flow rates and higher acceptable maximum pressures. Additionally, low-flow forelimbs have less cellular damage than high-flow forelimbs based on oxygen uptake, edema, potassium levels, and histology through 2 hours of machine perfusion. These results are expected to inform future upper extremity VCA preservation studies.

AB - Vascularized composite allografts (VCAs) refer to en bloc heterogenous tissue that is transplanted to restore form and function after amputation or tissue loss. Rat limb VCA has emerged as a robust translational model to study the pathophysiology of these transplants. However, these models have predominately focused on hindlimb VCAs which does not translate anatomically to upper extremity transplantation, whereas the majority of clinical VCAs are upper extremity and hand transplants. This work details our optimization of rat forelimb VCA procurement and sub-normothermic machine perfusion (SNMP) protocols, with results in comparison to hindlimb perfusion with the same perfusion modality. Results indicate that compared to hindlimbs, rat forelimbs on machine perfusion mandate lower flow rates and higher acceptable maximum pressures. Additionally, low-flow forelimbs have less cellular damage than high-flow forelimbs based on oxygen uptake, edema, potassium levels, and histology through 2 hours of machine perfusion. These results are expected to inform future upper extremity VCA preservation studies.

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Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol

Abstract

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ATP-Bio: NSF Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio)

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Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol

Abstract

Bibliographical note

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ATP-Bio: NSF Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio)

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