Date of Award

August 2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Member

Brian W Booth

Committee Member

Heather Dunn

Committee Member

Angela Alexander-Bryant

Committee Member

Agneta Simionescu

Abstract

Breast cancer is one of the most common cancer diagnoses worldwide. In the United States, 1 in 8 women will be diagnosed with some form of breast cancer within their lifetime. Breast reconstructive surgeries are an important part of patient health and well being following tumor removal. Unfortunately, modern reconstructive techniques frequently result in surgical complications, such as infection and tissue necrosis. Breast cancer recurrence is also a serious concern for patients, occurring in 10-41% of patients after 5 years depending on the severity of the original diagnosis. Tannic acid (TA), a naturally occurring polyphenol and antioxidant, has been researched for use in a wide variety of biomedical applications due to its unique chemical structure. In certain concentrations, TA selectively induces apoptosis in ER+ and HER2+ breast cancer cells compared to non-tumorogenic mammary cells. TA has also demonstrated potent antimicrobial activity against common pathogenic bacterium like S. Aureus and E. Coli. TA has applications in biomaterials as a crosslinker due to its ability to form hydrogen bond between collagen fibers and other natural polymers and improve mechanical properties. Our lab has developed an injectable TA crosslinked collagen bead biomaterial with anticancer activity to create a multifunctional cell scaffold. The goal of the device is to be used for breast reconstruction, where patients’ isolated preadipocytes are grown on collagen beads in vitro before injection into surgical voids capable of fatty tissue regeneration as a replacement for lipofilling. As an injectable scaffold, it was key to first define the parameters for precise device manufacture, cell seeding, and injection in order to understand the relationship between TA concentration, bead size, and cell attachment. Following implantation, the safety and efficacy of the collagen/TA bead as a tissue regenerative implant and TA delivery system needed to be determined by assessing the biocompatiblity and cellular composition of the collagen/TA beads in vivo. Lastly, the degradation rate of the beads and changes in TA concentration overtime in vivo was analyzed to determine the longevity of the bead structure and TA release in vivo for potential antibacterial and anticancer activity.

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