Keywords

Cathepsin K; Alendronate; Hematoxylin and Eosin Stain; low-intensity pulsed ultrasound; Masson’s Trichrome Stain; nanobubbles

Abstract

In recent years, the field of nanomedicine has provided promising alternatives to traditional ways of gene and drug delivery, such as nanobubbles instead of viral vectors. Manufacturing these nanomaterials is cost-effective and tends to be safer than previous forms of treatment for clinical use. In the realm of osteoporosis, a disease based around a higher rate of bone resorption to bone formation, leads to weak and brittle bones, leaving sufferers at risk for fractures, which are sudden and unexpected. These fractures are estimated to cost USD 22 Billion annually in the US alone. Reports show a significant effect on the quality of life after these fractures. Osteoclast-inhibiting oral medicines have been used to slow down bone resorption, but they have had severe side effects. This project aimed to study the impact of nanobubbles synthesized to target bone and filled with CTSK-siRNA to silence the Cathepsin K gene in an ovariectomized mice model. Cathepsin K is pivotal in osteoporosis as it is responsible for collagen degradation in bone resorption. Low-intensity pulsed ultrasound (LIPUS) for nanobubble destruction to facilitate targeted CTSK-siRNA release. LIPUS can also promote bone formation. We studied the effects of the treatment through histological analysis. Microarchitecture in the mice femur was highlighted through different types of staining such as Masson’s Trichrome, Hematoxylin & Eosin, and tartrate-resistant acid phosphatase staining. ImageJ was used for all measurements taken to interpret bone resorption in experimental groups. The major organs were studied to ensure the biocompatibility of nanobubble treatment. Our results show an increase in the average cortical thickness and trabecular spacing, but there was no significant increase in trabecular thickness in the group treated with CTSK-siRNA nanobubbles.

Thesis Completion Year

2024

Thesis Completion Semester

Spring

Thesis Chair

Razavi, Mehdi; Chiarelli, Tina

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Thesis Discipline

Biomedical Sciences

Language

English

Access Status

Open Access

Length of Campus Access

None

Campus Location

Orlando (Main) Campus

Available for download on Thursday, May 01, 2025

Included in

Nanomedicine Commons

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Rights Statement

In Copyright