135 Vital, Porcine Skin Xenotransplants Provide Safe and Efficacious Temporary Wound Closure of Severe Burns in a First-in-Human Phase I Clinical Trial

Abstract

Abstract Introduction Temporary wound closure with human allograft skin is considered the gold standard after early excision of a large burn injury. Limitations of allograft include availability, cost, and safety; thus, an alternative that provides the same quality with enhanced safety would be a valuable surgical adjunct to the clinical options currently available to treat severe and extensive full thickness burn wounds. A live cell skin xenotransplant from a clinical grade porcine donor is one candidate. Advantages of this alternative include retention of 70% or more of the innate metabolic activity following cryopreservation, vascularly favorable dermal thickness, and genetic modifications that eliminate hyperacute graft rejection. Combined, these result in pliability, strength, survivability, and function that far exceed those of conventional xenografts and mirror those of human allograft. Methods Split-thickness skin xenotransplants containing vital dermal and epidermal cells were aseptically procured from alpha-galactosyltransferase knockout porcine donors from a closed, Designated Pathogen Free, colony. They were then processed to achieve both sterility and cellular viability and cryopreserved for long term storage. In 2018, the FDA authorized a first-in-human Phase I clinical trial to evaluate the safety and tolerability of a genetically modified skin xenotransplant to treat severe and extensive burn wounds. A two cohort, open-label, dose-escalation study evaluated 6 consenting patients with severe burns requiring allograft. Each received surgical grafting with a skin xenotransplant and human allograft skin in a side-by-side, in-situ comparison. Results The skin xenotransplant was well tolerated by all patients, resulting in zero adverse events or safety issues, and without zoonotic disease transmission. In all cases, the skin xenotransplant appeared indistinguishable from the human allograft comparator and at the time of autografting, both were vascularized and fully adherent. These findings build upon the series of preclinical studies reported by these authors and presented at the ABA in 2019. Conclusions These highly promising patient outcomes demonstrate a potential treatment for complicated burns, especially when human allograft skin is unavailable. Further study of the efficacy of the porcine skin xenotransplants is warranted. As such, a multi-center, Phase II efficacy trial is planned for 2021.