Development of a Supercooled Limb Preservation Protocol
Abstract
The recent wars in Iraq and Afghanistan have resulted in >1500 amputations in wounded Warriors and approximately 500 have suffered multiple extremity amputations. Of 4000 or so facial injuries, around 50 were catastrophic. These statistics demonstrate the growing challenge of modern warfare in which improvements in body armor have reduced the number of fatalities in the field but conversely, reflect the limitations of conventional reconstructive surgery in restoring our Service members to health and wholeness. More importantly, the number of civilians with similar injuries resulting in limb loss or devastating craniofacial injuries is much greater -- of 2 million people living with limb loss, more than 185,000 amputations are performed annually; of 3 million facial injuries presenting to the emergency room each year, estimates suggest that 0.5% (15,000) are considered catastrophic and if just 1% (of the 15,000) are candidates for face transplantation, that translates to 150 new cases every year. The immense benefit of hand/face transplantation (i.e., vascularized composite allografts, VCAs) in restoring both the military and civilian populations has since been demonstrated successfully in more than 100 hand and 30 face VCA cases worldwide. A major limitation to wide application of VCA however is the extreme difficulty in finding matching donors. This is in stark contrast to solid organ transplants (e.g., kidneys, lungs, heart) in which the matching of donors and recipients is paramount to the longevity and function of both the transplant and patient. In fact, the matching of size, skin color, and gender currently take precedence in VCA. Additionally, VCAs are ethically, legally, and medically required to be taken from deceased donors (unlike in kidney and liver transplants). In turn, these requirements translate to a severe limitation in the potential number of VCA donors within geographic vicinity of a patient awaiting a limb/face transplant. One potential solution is to enable preservation of VCAs, so that patients on the waiting list have sufficient time for notification and travel. Preliminary animal and cadaveric studies on various tissue preservation technologies have demonstrated the potential for the viability of VCAs to be prolonged beyond the current limit of ~ 6 hours before irreversible tissue damage develops. Our institution has previously demonstrated that rat livers can be harvested from deceased donors, resuscitated with machine oxygen perfusion, and cold preserved for up to 72 hours before transplantation into recipients with 100% survival. Additionally, the prolongation of tissue viability may conceivably be applied to related fields such as trauma, such that amputated body parts may be recovered and preserved so that the patient can be stabilized before definitive surgery, and in bone marrow transplantation so that VCA patients have sufficient time to undergo recipient conditioning for immunologic tolerance (absence of destructive immune responses against transplanted tissues in the absence of immunosuppression) to develop. Thus, the objective of the current application is to adopt our previously successful liver preservation protocol in VCA studies using an established rat hindlimb model to mimic both hand and face transplantation (which consists of skin, muscle, nerve, and bone). The ability to do so would enable the well-described benefits of VCA to be extended to many more of our injured Service members and is the underlying rationale of this proposal. Restoring our war Veterans would also, in turn, be of immense psychosocial benefit not only to themselves but to their family members and caregivers. The proposed study will address the Fiscal Year 2016 Restorative Transplantation Research Technology Development Award Focus Area Improve ex vivo VCA tissue preservation techniques or technologies to extend the time between procurement and transplantation, with a goal of 24 hours. Su
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710680
Entities
People
- Curtis L. Cetrulo, Jr
Organizations
- Massachusetts General Hospital
- United States Army