Date on Master's Thesis/Doctoral Dissertation

5-2022

Document Type

Master's Thesis

Degree Name

M. Eng.

Department

Bioengineering

Committee Chair

Steinbach-Rankins, Jill

Committee Co-Chair (if applicable)

Frieboes, Hermann

Committee Member

Frieboes, Hermann

Committee Member

Altiparmak, Nihat

Author's Keywords

Metronidazole; 3D printed scaffolds; silicone scaffolds; drug release kinetics; bacterial vaginosis

Abstract

Sustained local administration of active agents has been proposed to cure bacterial vaginosis in the female reproductive tract and restore the resident bacterial fauna. Bioprinting has shown promise for the development of systems for local agent delivery. In contrast to oral ingestion, agent release kinetics can be fine-tuned by bioprinting specialized scaffold designs tailored for particular treatments while enhancing dosage effectiveness via localized sustained release. It has been challenging to establish scaffold properties for sustained release as a function of fabrication parameters. Towards this goal, we evaluate 3D printed scaffold formulation and feasibility to sustain release of metronidazole, a representative antibiotic. Silicone scaffolds were printed in a cylindrical design and cured using three different conditions relevant to potential future incorporation of temperature-sensitive labile biologics. Scaffold A was cured 4 hr at 50C followed by 72 hr at 4C, while Scaffold B was cured 4 hr at 50C followed by 24 hr desiccation at room temperature and Scaffold C was cured 24 hr at 50C. Drug release and compressive strength were monitored for 14 d in simulated vaginal fluid to assess long-term effects of fabrication conditions on release kinetics and mechanical integrity. Release profiles were vi fitted to previous kinetic models to differentiate potential release mechanisms. Scaffold A released 54.1% of drug over 14 d compared to 40.8% for Scaffold B and 33.7% for Scaffold C. Of six models evaluated, the Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin models best described the release, indicating similarity to release from insoluble or polymeric matrices. All scaffolds were axially and radially compressed to determine compressive strength and compressive Young’s modulus. For all metronidazole-containing scaffolds, similar axial and radial compression was observed between post-cure and 24 hr and 14 d groups. We conclude that 3D printed silicone scaffolds can provide sustained metronidazole release over 14 d, with release kinetics and compressive strength tuned by the fabrication parameters.

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