Multiparametric Bioreactor for Functional Preservation of Vascularized Composite Allografts
Abstract
Rationale and Objective: An estimated 40% of all combat casualties in Iraq and Afghanistan resulted in injuries to the extremities, face, head and neck structures. Epidemiological data from 2001-2011 found that there were 1760 craniofacial injuries in the Iraq and Afghanistan conflicts. For Service members surviving these devastating extremity injuries, prosthetic devices are currently the only established means of rehabilitation. Yet, 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 interactions. Most importantly, none of the currently existing available prosthetic devises is able to restore the patient’s ability to feel again. Vascularized composite allotransplantation (VCA) for severe trauma provides the ability to restore an individual’s missing hand, arm, or face. It is an innovative reconstructive technique with immediate clinical applicability and the potential to become a leading intervention for complex and traumatic injuries involving significant functional and psychological deficits. However, the use of VCA is severely limited by short organ and tissue preservation times (within 4-6 hours). Beyond this, VCA grafts suffer damage from tissue necrosis during the preservation time and increased ischemia-reperfusion injury following transplantation. Consequently, organ preservation plays a major role in improving the clinical outcome of transplantation. Novel technologies capable of preserving the viability and functionality of the various tissue components in VCA -- specifically, the muscle, nerve, and vasculature -- would significantly increase the efficacy of this treatment modality and facilitate more widespread applications of life-changing VCA. Extracorporeal perfusion systems have demonstrated incremental improvements in preserving porcine VCA viability. However, these perfusion systems do not sufficiently mimic the physiological microenvironment of VCA tissues or maintain their function. The proposed research will develop technologies under an Investigator-Initiated Research Award to provide a multiparametric bioreactor for the functional preservation of vascularized composite allografts with novel non-invasive biosensors that provide real-time assessments of the health of the VCA tissue and predict likelihood of graft success. Ultimate Applicability and Impact of the Research: VCA enables the complete reconstruction of complex defects in fewer (often one) surgical procedures than traditional reconstructive methods. There is a burgeoning need for technologies capable of extending the preservation period for VCA. The successful development of the technology proposed in this project could revolutionize conventional approaches of organ preservation in VCA and thereby maximize the beneficial impact of VCA. Our proposed system will be customized to specifically enhance VCA survival. Furthermore, the development of a technology platform for real-time assessment of the health of the graft and prediction for its survival in the recipient will dramatically transform the field of VCA preservation. Thus, implementation of this technology will enable more patients to benefit from receiving a reconstructive transplant, allowing them the functionality and sensation only a transplant can offer as well as enabling patients the potential to regain their identity and integrity and reintegrate into their respective family and social routines. Successful completion of this translational preclinical project would result in significant progress toward better preservation of VCA. However, the overall economic benefit of improving tissue preservation techniques for VCA is insuperable. In addition to transplantation, these techniques are applicable to any form of amputation/replantation and could allow maintenance of tissue viability after combat injuries including
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710287
Entities
People
- Gerald Brandacher
Organizations
- Johns Hopkins University
- United States Army