Theses and Dissertations

ORCID

https://orcid.org/0000-0001-5143-1722

Issuing Body

Mississippi State University

Advisor

Fitzkee, Nicholas C.

Committee Member

Emerson, Joseph P.

Committee Member

Mlsna, Todd E.

Committee Member

Thompson, Mathew

Committee Member

Johnson, Christopher N.

Date of Degree

12-13-2024

Original embargo terms

Worldwide

Document Type

Dissertation - Open Access

Major

Chemistry

Degree Name

Doctor of Philosophy (Ph.D.)

College

College of Arts and Sciences

Department

Department of Chemistry

Abstract

Biofilms on both the surface and interior of medical devices pose major challenges, including hindering device performance and serving as infection sources. These biofilms form a protective layer around bacteria, shielding them from the body’s immune system and antibiotics. This makes infections difficult to treat, as the bacteria within the biofilm are resistant to both antibiotics and immune defenses. Additionally, biofilms can induce inflammation and irritation in nearby tissues, leading to further health complications. Antibiotic resistance raises concerns about the emergence of multi-drug resistant (MDR) pathogens. MDR infections are difficult to treat, leading to prolonged hospital stays and the need for multiple treatments with broad-spectrum antibiotics. Nanotechnology offers an excellent platform for enhancing and developing antimicrobial agents and drug delivery systems for treating infectious diseases. This dissertation investigates the development of temperature-responsive nanospheres (TRNs) with high antimicrobial efficacy against biofilm-forming pathogens. These TRNs self-associate and agglomerate above a tunable transition temperature, achieved by functionalizing gold nanoparticles with elastin-like polypeptides (ELPs). Through protein design principles, a broad range of transition temperatures and photothermal conversion efficiencies are attained. TRNs exhibit reversible agglomeration under near-infrared (NIR) light, showing enhanced photothermal conversion efficiency and significant effectiveness in photothermal ablation of biofilms. This engineering approach enables the creation of a novel antibiofilm nanomaterial with low cytotoxicity. Additionally, a protein-based functionalization strategy targets biofilm extracellular matrices, utilizing gold nanoparticles with ELPs for biofilm targeting and low protein binding. Near-infrared laser irradiation results in a substantial improvement in killing efficiency compared to untreated controls. Furthermore, the study develops an affordable Dynamic Flow Reactor (DFR) model using 3D-printed materials to assess antibacterial nanomaterials' effectiveness. The DFR, incorporating copper-loaded filaments, inhibits biofilm growth on reactor surfaces, demonstrating resistance to biofilm formation while highlighting the potential of 3D printing in designing antimicrobial surfaces.

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