# Immunoengineering Strategies for Musculoskeletal Trauma

> **NIH NIH R01** · UNIVERSITY OF OREGON · 2020 · $516,331

## Abstract

PROJECT SUMMARY
Musculoskeletal trauma is highly prevalent in both combat-wounded and civilian patients, and despite advances
in trauma care, mortality and complication rates remain remarkably high. Patients who do not respond to
treatment or suffer from complications, experience poor healing, longer hospital stays, increased treatment costs,
and prolonged disability. Recently, systemic immune dysregulation and immunosuppression has been implicated
in the limited success of current intervention strategies and poor outcomes in trauma patients. Systemic immune
dysregulation and immunosuppression results in decreased levels of circulating pro-inflammatory cytokines and
a decrease in circulating immune effector cells, such as effector T cells. Another notable hallmark of systemic
immune dysregulation is elevated levels of immune suppressor cells, including myeloid-derived suppressor cells
(MDSCs). Our overall objectives are to investigate (i) how the development of systemic immune dysregulation
and immunosuppression relates to functional bone regeneration and (ii) how systemic immunomodulation
impacts the immune system and regenerative outcomes following severe musculoskeletal trauma. We will meet
these objectives through the following specific aims. SPECIFIC AIM 1: Characterize the development of
systemic immune dysregulation and immunosuppression in a pre-clinical composite trauma model and
identify immunological markers predictive of poor healing. Using a composite bone/muscle trauma pre-
clinical model, we will longitudinally characterize systemic immune dysregulation biomarkers via flow cytometry
and multi-analyte serum proteomic profiling and then utilize nonlinear evolutionary multivariate analytics to
develop predictive models of functional bone regeneration. SPECIFIC AIM 2: Fabricate and optimize an
immunomodulatory therapeutic to target and deplete MDSCs. We will develop synthetic gold nanoparticles
functionalized with both Fc-mimicking and MDSC-targeting ligands that can mimic mAb function (SNAbs) and
optimize their multivalency, Janus orientation, and size for MDSC depletion. SPECIFIC AIM 3: Evaluate the
effect of systemic immunomodulation on the immune system status and bone regeneration in vivo
following severe musculoskeletal trauma. We will test the hypothesis that targeted depletion of MDSCs will
restore immune homeostasis and promote functional bone regeneration.

## Key facts

- **NIH application ID:** 9974169
- **Project number:** 1R01AR074960-01A1
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** ROBERT E Guldberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $516,331
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974169

## Citation

> US National Institutes of Health, RePORTER application 9974169, Immunoengineering Strategies for Musculoskeletal Trauma (1R01AR074960-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9974169. Licensed CC0.

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