Thomas Turner

PhD Proposal Presentation

Date: May 5th

Time: 2-4 pm

Bluejeans Link: https://bluejeans.com/530197328

Thesis Advisor:

Edward A. Botchwey, PhD
 

Thesis Committee:

Andrés García, PhD

Valeria Milam, PhD

Andrew Neish, MD

Matthew Spite, PhD

Nick Willett, PhD

Title: Shifting the Balance of Inflammatory and Pro-Resolving Lipid Mediators in Volumetric Muscle Loss Injuries

Abstract:

Extremity trauma involving large tissue loss presents a significant clinical challenge for both general and military populations. In challenging cases resulting in volumetric muscle loss (VML), the current gold standard treatment is surgical reconstruction with muscle flap autografts or free tissue transfer. However, excessive fibrosis and fatty infiltration frequently impair regeneration and lead to significant long-term disabilities and chronic pain. The overarching hypothesis of the proposed research is that critical VML injuries have a dysregulated inflammatory lipid-mediator response, characterized by an abundance of pro-inflammatory mediators compared to pro-resolving mediators (SPMs), that impairs the regenerative capacity of muscle. Furthermore, the local delivery of SPMs in combination with the sequestration of pro-inflammatory lipid mediators will promote the timely resolution of inflammation and activate endogenous pathways of muscle regeneration. We have established a modular polyethylene glycol-maleimide (PEG-4MAL) biomaterial platform that can: 1) enable controlled release of aspirin-triggered resolvin D1 (AT-RvD1) or docosahexaenoic acid (DHA), an SPM precursor, to induce pro-resolving immune subsets, and 2) serve as a scaffold to sequester pro-inflammatory mediators using oligonucleotide aptamers. We will test whether sequestration of pro-inflammatory mediator LTB4 in aptamer functionalized PEG-4MAL hydrogels promotes inflammation resolution and enhances muscle regeneration following VML used alone or in combination with AT-RvD1 or DHA delivery.