Grants Funded

Abstract

Impact Statement: The incidence of traumatic limb amputation in the civilian and military setting has been steadily increasing. The quality of life of upper limb amputees is impaired by physical disability, pain, changes in occupational status, and short- or long-term complications. A major limitation to successful replantation and transplantation of extremities is the lack of an adequate technology capable of preserving tissue viability. This work will result in the development of the first portable EVNLP machine to preserve human limbs following amputation. EVNLP machine will allow longer preservation, assessment of limb viability and prevent damage caused by cooling. Decreased ischemia prior to transplantation is expected to reduce acute and chronic rejection and improve the overall functional outcomes.

Project Summary: Traumatic amputations of upper extremities affect thousands of lives in the USA each year. Both immediate replantation and delayed transplantation from a donor are reconstructive options that lead to better function and higher satisfaction rates than a prosthesis. Currently, the only available limb preservation strategy following amputation is cold storage, which can cause additional injury to limb tissues and does not allow assessment of the limb during the limited preservation period. Ex vivo normothermic limb perfusion (EVNLP) maintains the limbs in near physiologic conditions providing oxygen and nutrients. EVNLP can prevent the injury caused by the cold storage and warm ischemia and extend preservation times. The purpose of this study is to achieve portability and automation of the EVNLP system. Milestone 1-To develop an automated portable EVNLP machine for extended preservation of upper extremities. Task 1- To integrate the perfusion core and monitoring unit in a portable EVNLP system. The EVNLP system will be assembled in a custom built aluminum enclosure, using impact resistant connectors to minimize vibration during transportation. The monitoring unit will be integrated for real-time data acquisition. Five perfusate-only tests will be performed to evaluate the outcome measures over time. Task 2- Test the portable EVNLP machine performance using porcine limb perfusion studies. EVNLP system performance will be tested using three porcine limb perfusion studies for 12 hours in preparation for human studies. Milestone 2- To test EVNLP machine performance during human limb perfusion in transport scenario (1 task). The performance of the portable EVNLP machine during transport will be evaluated in collaboration with the Cleveland Clinic Critical Care Transport Department. The portable EVNLP machine will maintain perfusate flow, pressure, and oxygenation and provide automated detection of the key parameters during perfusion of three human upper limbs in transport settings. This task will allow us to identify component/machine failure and to optimize the performance of the EVNLP machine. The proposed study will deliver an EVNLP machine that is mobile, with automated monitoring, that will allow us to file an FDA application for a “first in human” pilot study on the safety and feasibility of ex vivo perfusion in traumatic and elective amputations of human upper extremities.

Biography
In the past ten years I have accumulated extensive experience in clinical and experimental reconstructive microsurgery as well as in hand and craniofacial surgery. This background allowed me to focus toward vascularized composite allotransplantation. The highlights of my career include: 1. Participation in 2 hand transplant procedures at Christine Marie Kleinert Institute (Louisville, KY). I was directly involved in the care of the hand transplant recipient. 2. Follow up of the first face transplant performed at Cleveland Clinic. In December 2008, Cleveland Clinic performed first, near-total face transplant in the United States. At the time, it was considered the largest and most complex face transplant in the world. The second face transplant was performed in September 2014. My role involved preparation of the donor and recipient and follow up of the recipient postoperatively. This great opportunity resulted in the authorship of several peer–reviewed publications and book chapters. 3. 2015 Kawamoto Award for the best paper presented at the 71 Annual Meeting of the American Cleft Palate-Craniofacial Association. I received this highly competitive award for a paper entitled: Retrieval of a full facial allograft based on the maxillary artery: indications and technique. 4. My overall research experience includes: 44 peer-reviewed publications, 8 book chapters, and over 80 conference presentations.