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

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.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Drs. Lellouch, Cetrulo, Uygun, Tessier, and Ms. Pendexter have provisional patent applications relevant to this study. Drs. Uygun and Tessier are on the scientific advisory board, are cofounders, and have financial interest in Sylvatica Biotech Inc. which aims to develop technology that stops or controls biological time. All competing interests are managed by Mass General Brigham in accordance with their conflict of interest policies. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(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.)