Date of Award

May 2021

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Bioengineering

Committee Member

Brian Booth

Committee Member

Heather Dunn

Committee Member

Agneta Simionescu

Abstract

Among women, breast cancer is the most commonly diagnosed cancer in the United States, affecting about 1 in every 8 women. It accounts for approximately 30% of new cancer diagnoses and is one of the leading causes of cancer-related deaths among women in developed countries. Current treatment options for breast cancer are surgery, chemotherapy, and radiation. Unfortunately, there are negative side effects associated with each of these, and they may not work for every patient. In addition, local breast cancer recurrence presents a high risk, especially for patients undergoing lumpectomy procedures. The goal of this project is to alleviate these problems by developing an injectable bead scaffold to promote tissue regeneration in the void created by lumpectomy, as well as to prevent local recurrence and minimize surgical-related infections. Microbeads were synthesized from collagen type I and crosslinked with tannic acid to form the basis for this injectable therapeutic. Tannic acid acts as a therapeutic anticancer agent by inducing apoptosis in breast cancer cells via caspase pathways and has demonstrated antimicrobial properties. The collagen/tannic acid beads were seeded with adipocytes to attach and grow onto the matrix, then release the tannic acid into the surrounding environment as the attached cells remodel the collagen. To prove the viability of this therapy, an in vivo study was conducted using a pig model. Beads were injected orthotopically into the mammary glands, then excised at three time points for histological analysis. Tissue samples were fixed, embedded in paraffin, and sectioned and stained with various methods to determine cell types present. Additionally, samples of the kidneys and livers were collected for toxicity analysis. Our results indicate that the collagen beads were successful at promoting tissue regeneration, specifically by increasing expression of VEGF and presence of adipocytes, intermediate filaments, and smooth muscle actin.

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