Advancement of a Tissue Oxygenation Measurement Device and Evaluation of Galectin-3 as Novel Noninvasive Prognostic Biomarkers for Monitoring VCA Rejection
Abstract
Objectives: After severe trauma to the extremity or the face the current technology available to reconstruct the wounded Warrior consists of taking tissue from non-injured portions of the body to reconstruct what has been lost. These surgical techniques are often inadequate to completely restore the patient to their pre-injury status. In addition, wounded warriors often require multiple revision procedures, prolonged rehabilitation, and complications and functional restrictions that occur because of harvesting the graft from the patient’s own body. In those cases where no like tissue exists, such as in the case of a lost hand or leg, a prosthesis would be the main option. One potential solution to the overwhelming need for tissue for reconstruction is the use of tissue (such as a hand) taken from deceased donor and transplanted to the living recipient. These types of transplants are called vascularized composite tissue allografts (VCAs), as they include multiple tissue types such as bone, tendon, muscle, and skin together with the vasculature that supplies blood to these tissues. To prevent rejection and loss of these transplants, immunosuppressive drugs are given to the VCA recipients for the remainder of their lives (as is used in kidney and other organ transplants). Increased doses of immunosuppression can resolve acute rejection episodes; however, once chronic rejection becomes clinically obvious it is often too late to control it by adjusting immunosuppression. In addition, serious life-threatening complications can occur due to the immunosuppressive drugs themselves. Since VCA transplantation is not generally a life-saving procedure, prolonged high-dose immunosuppression is not acceptable. Despite the use of maintenance immunosuppression, all VCA patients have experienced multiple episodes of rejection. The objective of this proposal is to validate novel approaches for frequent non-invasive monitoring of VCA recipients to detect early signs of rejection without needing to perform skin or muscle biopsies. Frequent non- invasive assessment would allow clinical adjustments to immunosuppressive drug therapy early enough to avoid clinically significant rejection episodes and prevent the progression to chronic rejection. Rationale: Damage to the blood vessels within the graft is an early sign of VCA rejection. Blood vessel damage will result in less blood flow decreasing the amount of oxygen that can reach the graft tissue. We propose to further develop a novel tissue oxygen sensing device suitable for at home monitoring that can accurately detect subtle decreases in VCA tissue oxygenation compared to healthy skin. A decrease in oxygen is known to cause an increase in expression of a particular protein found in the blood, galectin-3, in various inflammatory disease states. Accurate measurement of a decrease in tissue oxygenation specific to the graft tissue in combination with an increase in circulating galectin-3 levels could provide an early indication of graft blood vessel damage before any visible skin changes occur. Early detection would allow guided tailoring of immunosuppression to avoid progression to acute or chronic rejection. FY21 RTRP Advanced Technology Development Award Focus Areas: This proposal directly addresses the FY21 RTRP Advanced Technology Development Award Focus Areas: Advance reliable non-invasive prognostic/diagnostic biomarkers, methods, or tools for monitoring VCA graft rejection, including applications that would be suitable for point-of-care testing or home monitoring; Develop reliable non- invasive biomarkers for monitoring chronic VCA graft rejection in a large animal model; and Validate new peripheral biomarkers for acute and chronic rejection. Applicability and Impact of the Product: If results of this study validate the use of the oxygen sensors and/or peripheral galectin-3 levels as predictive biomarkers for VCA rejection, both approaches can be immediat
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210928
Entities
People
- Conor L Evans
Organizations
- Massachusetts General Hospital
- United States Army