Perfusion decellularization for vascularized composite allotransplantation

Danielle L Nicholls; Sara Rostami; Golnaz Karoubi; Siba Haykal

doi:10.1177/20503121221123893

Perfusion decellularization for vascularized composite allotransplantation

SAGE Open Med. 2022 Sep 13:10:20503121221123893. doi: 10.1177/20503121221123893. eCollection 2022.

Authors

Danielle L Nicholls¹, Sara Rostami², Golnaz Karoubi^{2

3}, Siba Haykal^{2

4}

Affiliations

¹ Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
² Latner Thoracic Surgery Laboratories, Toronto General Hospital Research Institute, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
³ Departments of Mechanical and Industrial Engineering and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁴ Division of Plastic & Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.

Abstract

Vascularized composite allotransplantation is becoming the emerging standard for reconstructive surgery treatment for patients with limb trauma and facial injuries involving soft tissue loss. Due to the complex immunogenicity of composite grafts, patients who undergo vascularized composite allotransplantation are reliant on lifelong immunosuppressive therapy. Decellularization of donor grafts to create an extracellular matrix bio-scaffold provides an immunomodulatory graft that preserves the structural and bioactive function of the extracellular matrix. Retention of extracellular matrix proteins, growth factors, and signaling cascades allow for cell adhesion, migration, proliferation, and tissue regeneration. Perfusion decellularization of detergents through the graft vasculature allows for increased regent access to all tissue layers, and removal of cellular debris through the venous system. Grafts can subsequently be repopulated with appropriate cells through the vasculature to facilitate tissue regeneration. The present work reviews methods of decellularization, process parameters, evaluation of adequate cellular and nuclear removal, successful applications of perfusion decellularization for use in vascularized composite allotransplantation, and current limitations.

Keywords: Perfusion; decellularization; recellularization; vascularized composite allotransplantation.

Publication types

Review