A Guide to the Implementation and Design of Ex Vivo Perfusion Machines for Vascularized Composite Allotransplantation

Dear Editor-in-Chief, We read the article titled “A Guide to the Implementation and Design of Ex Vivo Perfusion Machines for Vascularized Composite Allotransplantation” by Muss et al1 with particular interest. We greatly appreciate their contribution to this topic only explored by a few expert teams worldwide. We strongly share the thoughts of the authors regarding the potential of machine perfusion (MP) techniques in enhancing vascularized composite allotransplantation (VCA) outcomes. As also judiciously suggested, we believe MP techniques can also be implemented for flap-based autologous reconstruction. We recently demonstrated the benefits of intermittent perfusion in porcine fasciocutaneous flaps,2 providing better outcomes than continuous perfusion by protecting against endothelial injuries, interstitial edema, vascular resistance increase, and weight gain, which are critical parameters for successful perfusion.3 These preliminary outcomes aim at improving the reliability of MP-based last resort flap reconstructions as described by Wolff et al,4 marked by frequent ischemic complications. Regarding the perfusion temperature, we wish to pursue the authors’ discussion: Hypothermic perfusion is probably of little relevance in the case of muscle-free VCA and flaps because the resulting metabolic demand is low, greatly decreasing the interest of this technique. Therefore, we wish to further highlight the interest in subnormothermic MP (SNMP), which presents multiple advantages in a clinical setting. SNMP allows the use of bloodless and hemoglobin-free perfusates, greatly facilitating their implementation in the clinic and decreasing the infectious and immune risk for the patient. Moreover, because no dedicated MP systems are readily available for VCA, room-temperature SNMP allows the glimpsing of light equipment without the need for heat exchange systems. In our experience, SNMP combined with hollow-fiber oxygenators delivered optimized perfusion of fasciocutaneous flaps. The hollow-fiber oxygenator system also avoided using bubble traps by providing integrated filtration. Finally, another critical point emphasized by the authors is oxygen monitoring. Although tissue oximetry allows easy and real-time monitoring of the perfused organ oxygenation, it presents several drawbacks, including low precision and dependence on oxygen carrier–based solutions (mostly limited to normothermic MP). To circumvent the limitations of regular circulating pO2 sensors, we designed a 3-device system5 based on O2-sensing metalloporphyrin technology, achieving simultaneous and real-time monitoring of the inflow, outflow, and tissue oxygenation (Fig. 1). This system is adapted to any MP setting because it allows direct pO2 measurements. Besides the importance of O2 monitoring, we demonstrated the correlation between multichannel measurements and critical parameters such as vascular resistance.Fig. 1.: Three-channel system for continuous oxygen monitoring (pO2) during fasciocutaneous flap/VCA SNMP. Two 3-dimensional-printed flow cells enable monitoring of the inflow and outflow circulating perfusate, and a transcutaneous sensor based on the same oxygen-sensitive metalloporphyrin provides tissue oxygenation values. All real-time values are displayed on a laptop, and feedback loops are possible through the roller pump to continuously adapt the flow.In conclusion, we congratulate the authors on this precious contribution to the field of VCA and organ preservation and hope this supplementary discussion will help the development of Food and Drug Administration–approved MP systems designed for VCA and microsurgical flaps, eventually providing a new step to the reconstructive ladder. DISCLOSURES Berkane and Lellouch have a patent related to the technology described in Figure 1. The other authors have no financial interest to declare in relation to the content of this article.