DOI

https://doi.org/10.25772/B7K9-JZ16

Author ORCID Identifier

https://orcid.org/0009-0002-3337-3092

Defense Date

2025

Document Type

Thesis

Degree Name

Master of Science

Department

Biomedical Engineering

First Advisor

Rebecca Heise

Second Advisor

René Olivares-Navarrete

Third Advisor

Michael Hindle

Abstract

Acute respiratory distress syndrome (ARDS) is a prevalent, life-threatening lung condition, affecting nearly 200,000 Americans annually, with a 40% international mortality rate. There is no cure for ARDS, and current pharmacological treatments have limited effectiveness. Symptoms can be mitigated with mechanical ventilation, though this often leads to ventilator-induced lung injuries (VILI) and puts critically ill patients at risk of infections, including ventilator-associated pneumonia (VAP). A promising therapeutic is the extracellular matrix (ECM), a complex network of structural proteins and bioactive molecules that has been shown to have anti-inflammatory properties and prevent fibrosis. We aim to utilize the regenerative and immunomodulatory effects of decellularized extracellular matrix (dECM) obtained from both pig lung (PL) and mouse mesenchymal stromal cell (mMSC) matrices. Through various fabrication methods, we have found that dECM particles have a wide range of immunomodulatory and antimicrobial properties. The mMSC and PL dECM nanoparticles were fabricated via electrospray deposition with tunable sizes ranging from 145-275 nm and negative zeta potentials (~ -11 mV), giving them the ability to reach distal respiratory regions and penetrate the surfactant and mucus membranes in the lungs. We also fabricated an aerosolized powder of PL dECM via spray drying, which has shown similar pro-regenerative effects on damaged tissue. We found that the mMSC ECM nanoparticles have a dose-dependent bacteriostatic effect on gram-negative bacteria strains, inhibiting the growth of common pneumonia-causing pathogens Pseudomonas aeruginosa and Escherichia coli. Both the mMSC dECM nanoparticles and PL dECM spray-dried particles have demonstrated accelerated wound healing on injured cultures of both mMSCs and human lung epithelial cells. Our mMSC ECM treatments demonstrated immunomodulatory properties that show promise in suppressing inflammation and promoting resolution in a pro-inflammatory induced environment. Due to the versatile formulation options and matrix sources, our ECM particles can be tailored for different lung applications and demonstrate improved healing of injured lungs while inhibiting bacterial growth, making them a promising therapeutic biomaterial for aiding VAP recovery and treating ARDS patients.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-12-2025

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