Using Bioinspired Next-Generation Cryoprotectants to Advance Ex Vivo Preservation of Vascularized Composite Allografts at High Subzero Temperature
Abstract
The Problem: Losing an arm or a leg is a traumatic injury with lifelong after-effects that greatly damage a person’s quality of life, both physically and mentally. Most often, loss of a limb is the result of a horrific accident, unavoidable medical concern, or a traumatic event while in Service to the United States, compounding the problem further. Improved personal protective equipment and injury response protocols have greatly increased the survival rates of Warfighters who subsequent suffer from the most complex injuries. Yet, since 2001, about 1,650 U.S. troops have lost hands, arms, legs, or feet during the wars in Iraq and Afghanistan. Unfortunately, roughly 30,000 traumatic amputations occur in the U.S. every year, and it has been estimated that there will be >900,000 survivors of traumatic amputations living in the U.S. by 2020. Typical treatment is to use prosthetic devices (mechanical, artificial limbs) as a replacement. Leg prostheses offer excellent functional return and mobility and have even allowed Wounded Warriors to return to active duty. In contrast, even the most advanced upper-limb prostheses have failed to optimally restore the multiple and complex functions of a human hand in daily activities, social expression, and professional and social interaction. Medical advances such as Vascularized Composite Allotransplantation (VCA) exist to transplant donated limbs onto the body of the injured person, just like a kidney or heart transplant. This type of surgery is the only treatment option to fully restore missing limbs with functioning tissue that represents your own original arm or leg. In particular, for such devastating combat and civilian injuries where conventional reconstruction is not achievable, VCA, most commonly in the form of hand, arm, or face transplantation, has become a viable alternative and an exciting new treatment option. Major advances are being made to ensure the new limb can remain healthy and functional for the patient’s entire life with reduced immunosuppressive drugs. However, more be done. One major issue to be addressed is the lack of donor limbs available today to support and heal injured patients. In fact, there is a critical need to improve the technology used to preserve donated limbs so that they can be moved from donor to patient without having the donated limb expire during transport. Currently, human extremities generally only survive 4-6 hours before they are no longer healthy enough for transplant. Objective: To extend limb survival time and transport, we can store the limb below freezing temperature, but we need to prevent damage from freezer burn, similar to when meat or ice cream is stored too long in the freezer. This work proposes to use new safe, non-toxic chemical technologies to safely store whole forelimb grafts below freezing temperature, without freezer burn damaging the limb. This new technology has been strikingly successful in preliminary small- and medium-sized organ preservation and transplantation studies. Surgeons and scientists will transplant preserved animal limbs and compare function. This will be the first proof of concept to improve forelimb and hind-limb transplants using tissue that has been stored for extended time periods of up to 3 days. This project directly addresses the RTRP FY20 Focus Area to advance existing or develop innovative ex vivo tissue preservation strategies to extend the timeline between procurement and transplantation. What It All Means for You: Success in this work could lead to major medical advancements within the next 5 years to preserve transplantable limbs, hands, and other tissues and organs for extended lengths of time, up to multiple days before transplantation, with the potential to significantly reduce geographic restrictions between donor and patient and increase the likelihood of finding a suitable donor, as well as eventually facilitate desensitization and tolerance strategies to r
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110734
Entities
People
- Gerald Brandacher
Organizations
- Johns Hopkins University
- United States Army