# Brain death associated vascularized composite allograft injury and its impact on alloimmunity and functional recovery

> **NIH NIH R56** · UNIVERSITY OF FLORIDA · 2021 · $337,831

## Abstract

Project Summary: Face and limb vascularized composite allograft (VCA) transplantation (Tx) is not only
feasible, but can be a superior method of restoring the aesthetics and function of complex structures. Despite
the recent strides made in the technical aspects of VCA Tx, there is still an urgent need to develop novel
approaches to improve graft function and survival. However, VCAs generate a strong immunological response,
and recipients require life-long aggressive immunosuppression to prevent rejection. This places the recipient at
substantial risk and shortened life expectancy due to the high toxicity of immunosuppressive drugs. Significantly,
immunosuppressives are neurotoxic and can impair neuroregeneration, leading to poorer graft
functional recovery. Given this, and because VCA Tx is usually life-changing, but not lifesaving, a principle
research goal, and one that is addressed herein, is the development of novel strategies that not only facilitate
the use of immunosuppressive sparing regimes but also enable neurogenesis and graft functional recovery.
While T cell-mediated rejection is central to graft rejection, studies in solid organ transplant (SOT) have identified
the early post-transplant graft injuries of brain death (BD) induced injury and ischemia reperfusion injury (IRI),
as key primers of the alloimmune response. Whether BD and IRI play similar roles in VCA has not been
investigated. Both BD and IRI are unavoidable early events in the VCA Tx process. We propose to investigate
the role of these acute pre and post-transplant injuries on the shaping of an alloimmune response and the
consequences thereof on graft rejection, functional recovery, and dose of immunosuppressive required to
prevent T-cell mediated rejection. Our working hypothesis is that reducing BD induced injury and IRI will reduce
graft alloresponsiveness and improve nerve regeneration and repair, thus enabling the more widespread
application of this life-changing procedure. Specifically, we will: 1. Characterize a novel targeting approach for
delivery of a complement inhibitor to VCAs, and 2. Determine the role of BD, C and early allograft injury on an
acute alloimmune response, the parameters of required immunosuppressive therapy, and functional hindlimb
recovery. The potential impact of this proposal is far-reaching as success in reducing early graft injury and
rejection, while promoting functional recovery, has the potential to expand the utilization of this life changing
procedure. Furthermore, the therapeutic approaches investigated and mechanistic insights gained will likely have
implications for multiple transplantation procedures.

## Key facts

- **NIH application ID:** 10399007
- **Project number:** 7R56AI156383-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Carl Atkinson
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $337,831
- **Award type:** 7
- **Project period:** 2020-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399007

## Citation

> US National Institutes of Health, RePORTER application 10399007, Brain death associated vascularized composite allograft injury and its impact on alloimmunity and functional recovery (7R56AI156383-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399007. Licensed CC0.

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