Covalent Tethering of LL-37 onto Titanium Can Reduce Bacterial Colonization

Date of Award

8-2024

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Christopher S. Adams

Second Advisor

Brian J. Balin

Third Advisor

Michael P. McGuinness

Abstract

Introduction Periprosthetic infection is the leading complication of artificial joint replacement surgeries. Much previous work has demonstrated the efficacy of creating a metal surface that is resistant to bacterial colonization. LL-37 is a naturally occurring antimicrobial peptide found in humans. We suggest that tethering LL-37 to titanium might also create a surface resistant to bacterial colonization.

Methods To tether LL-37 to titanium surfaces, we modified a previously developed protocol with short pieces of titanium alloy wire as a model surface. In comparison to the LL-37 tethered surface, we also used a positive control by tethering Vancomycin, an antibiotic, to these model pins. Immunostaining methods were used to confirm the presence of LL-37 and Vancomycin on the titanium alloy pins. Successfully tethered pins were challenged against the two most common bacterium associated with periprosthetic infection: S. aureus and E. coli. Results were determined via colony counting and Live-Dead staining of the adherent bacteria as imaged by confocal microscopy.

Results and Discussion Our results have shown the presence of both LL-37 on the model surfaces. Our bacterial challenge experiments demonstrated effective prevention of bacterial colonization by both the Vancomycin and LL-37 tethered surfaces. Thus, LL-37 tethered to titanium alloy may provide an effective treatment for the prevention of periprosthetic infection. Further research should focus on optimization of the tethering reaction and evaluate the biocompatibility of the tethered surface.

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