A Novel Universal and Portable Normothermic Machine Perfusion Device for Vascularized Composite Allografts
Abstract
In recent wars, incidence of trauma to the extremities and face is significant: up to 40% of those wounded in recent combat had injuries to the extremities. Many of our armed Servicemen and Servicewomen experience severe injury to the arms, face, and groin that can result in significant disability and disfigurement. Vascularized composite allotransplantation (VCA) is a field that offers reconstruction of devastating traumatic injuries, such as upper extremity loss or severe facial trauma, using transplantation to replace like with like tissue. In cases where injury is so severe that conventional reconstructive efforts are ineffective at restoring sufficient function and appearance to allow for significant improvement in quality of life, VCA is becoming increasingly more prevalent. With over 200 VCAs performed worldwide, this burgeoning field continues to improve in both functional outcomes and immunologic treatment. However, there are still multiple significant hurdles in expanding the field for a more widespread reach to be able to treat more recipients in need of VCA. Because of the nature of the transplant, donors need to be matched for things such as size and appearance along with traditional need for immunologic matching, considerably decreasing the availability of upper extremity or facial transplants. With current techniques, the sensitive tissue of VCAs are only viable for a short number of hours from the time of procurement from the donor to when blood flow is restored as it is surgically reconstructed on the recipient. While strategies exist to decrease risk of rejection, they become increasingly difficult when there is tissue injury to the graft. This time constraint also substantially limits the geographic region for possible donors. In solid organ transplant, such as kidney and liver, strategies exist to increase the time before needing to restore blood flow, or the ischemia time. These strategies include cryopreservation, hypothermic perfusion, and normothermic machine perfusion (NMP). The approaches requiring tissue cooling over a prolonged period of time – cryopreservation and hypothermic perfusion – can lead to more tissue damage, which with such sensitive tissue including muscle and skin involved in a VCA, can cause more immune response and risk of rejection. However, other organs have had success with NMP increasing ischemic time without significant tissue damage. In preliminary studies, we have found that NMP is feasible in maintaining swine facial grafts with good maintenance of tissue integrity. In this study, we propose to improve the clinical practicality of our NMP approach in two major ways: (1) to produce a portable NMP system that can be universally applied to both face and limb grafts and (2) to apply machine learning (ML), a form of artificial intelligence to continuously control perfusion and evaluate graft health from donor to recipient. This project is responsive to the RTRP Focus Area to advance preservation strategies for VCA increasing the feasible time between procurement and transplantation by using promising translatable approaches, including perfusion. We will accomplish this outcome by a developing and producing a portable NMP system incorporating ML controls that avoids the pitfalls of constant in-transit operator vigilance required by extant NMP systems. We will test on swine hemifacial and limb grafts that we will transplant. Based on those transplant studies, we will apply machine learning to automated NMP and transplantation of faces and limbs in the swine model. In following the transplanted tissues, we will show that the system allows for rejection-free survival of VCA. We will include tests on multiple cadaveric human facial grafts to validate the optimal perfusion system. Initial clinical application via the Humanitarian Device Exemption could be realized as early as 2026. The impact of this study will be far-reaching. It will eliminate much o
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210725
Entities
People
- John Brassil
Organizations
- United States Army