Pre-treatments of Ex vivo Vascularized Composite Allografts: A Scoping Review

Baker, C. E.; Stead, T. S.; Shah, A. R.; Pullmann, D.; Chinta, S.; Tran, D. L.; Brydges, H. T.; Laspro, M.; Gelb, B. E.; Rodriguez, E. D.; Rabbani, P. S.

doi:10.1101/2024.11.20.624373

bioRxiv · 10.1101/2024.11.20.624373

Pre-treatments of Ex vivo Vascularized Composite Allografts: A Scoping Review

Baker, C. E.·Stead, T. S.·Shah, A. R.·Pullmann, D.·Chinta, S.·Tran, D. L.·Brydges, H. T.·Laspro, M.·Gelb, B. E.·Rodriguez, E. D.·Rabbani, P. S.

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Abstract

PURPOSEThe various physiological profiles comprising vascularized composite allografts (VCAs) pose unique challenges to preservation. Minimizing ischemia, reperfusion injury, and rejection remains a primary focus of graft pre-treatments (PTs). Currently, the gold standard PT consists of flushing the graft and placing it in static cold storage in the University of Wisconsin solution. With this method, graft viability is limited to four to six hours. Prolonging this time limit will increase donor allocation radius, access to care, and positive patient outcomes. We aimed to evaluate novel PTs that could potentially enhance and lengthen VCA viability. METHODSFollowing PRISMA guidelines, we conducted a comprehensive literature search of Embase, Cochrane, and PubMed. Studies had to be published prior to June 15, 2022. PTs had to target cell physiology, rather than immunogenicity. We extracted data including study design, PT details, evaluation metrics, and outcomes. RESULTSWe identified thirteen studies, categorized into three groups: solution-based alterations to the gold standard, ex vivo perfusion, and other novel techniques. The incorporation of hydrogen sulfide and Perfadex as solutions in the gold standard protocol demonstrated a six-day delay in rejection and limited reperfusion injury markers, respectively. In one ex vivo perfusion study, after 24 hours of PT and 12 hours post-transplant, VCA muscle contractility remained close to normal. The gold standard PT did not demonstrate the same success. However, graft weight gain, up to 50% of baseline among the articles reviewed, is a prominent side effect of perfusion. Another technique, cryopreservation, displayed 90% graft failure by venous thrombosis, despite high free graft viability following two weeks of storage. CONCLUSIONSThis study of pre-treatment modalities found a variety of encouraging preservation techniques for grafts with high levels of tissue diversity. Ex vivo perfusion dominated PT innovation with promising results in preserving the viability and functionality of muscle, which is central to the restoration of movement. Future studies are necessary to evaluate long-term graft outcomes and to optimize PT protocols for extended preservation times to ensure clinical relevance.

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Baker, C. E., Stead, T. S., Shah, A. R., Pullmann, D., Chinta, S., Tran, D. L., Brydges, H. T., Laspro, M., Gelb, B. E., Rodriguez, E. D., Rabbani, P. S.. 2024-11-21. Pre-treatments of Ex vivo Vascularized Composite Allografts: A Scoping Review. https://doi.org/10.1101/2024.11.20.624373

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