Date of Award

12-2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Advisor

Burg, Karen J.L.

Committee Member

Booth, Brian

Committee Member

Webb, Ken

Committee Member

Lee, Jeong Soo

Abstract

Breast cancer is the second most common cancer amongst women, second only to lung cancer. In 2014, it was estimated that there were approximately 295,000 new cases of breast cancer diagnosed in women, with approximately 40,000 deaths caused by breast cancer in the United States. It has been reported that a woman has a 12% chance of developing breast cancer in her lifetime and a 3% chance of dying from breast cancer. There are several treatment options available for breast cancer, including chemotherapy, radiation therapy, as well as two different forms of surgery, mastectomy and lumpectomy. However, none of these treatment options is perfect and there is even a chance of cancer recurrence after a patient undergoes one or more of these treatments. The long-term goal, beyond the scope of this project, is to significantly reduce the chances of cancer recurrence after a patient has undergone a lumpectomy. Currently, the chance of recurrence for a patient who undergoes a lumpectomy is around 10%. Furthermore, there is not currently an option for breast reconstruction for a lumpectomy patient. The proposed research will explore a possible approach to reducing the cancer recurrence rate as well as filling the void within the breast that was created by the lumpectomy with the patient's own tissues. The approach will include the use of tannic acid (TA) as a novel cross-linking agent for collagen scaffolds that will be used to encourage the attachment and growth of the patient's own cells, resulting in the regeneration of tissue to fill the void. As the cells remodel the scaffold, the tannic acid will be released into the surrounding tissue. In addition to tannic acid's cross-linking abilities, tannic acid has also been shown to have anti-cancer properties which will be used to neutralize any cancer cells that may still be present within the breast. This will effectively reduce the chances of recurrence for the patient. The focus for this research was on the evaluation of an in vitro model of a lumpectomy site which will used to test the efficacy of collagen beads that have been cross-linked with tannic acid. Beads cross-linked with TA concentrations of 0.1%, 1.0% and 10.0% were evaluated during the course of these studies. These beads were first evaluated using a 2D lumpectomy model and the results showed that the 1.0% and 10.0% TA beads were able to cause a higher incidence of apoptosis in cancer cells compared to preadipocytes. The 0.1% TA beads were able to support preadipocyte cell attachment and growth throughout the duration of the studies. The 1.0% TA beads were initially able to support cell growth but after 72 hrs, the level of viable cells greatly decreased. The studies then progressed to 3D cell culture techniques using collagen/ agarose gels with cancerous cells embedded within. The gels were then exposed to the different bead types. The 1.0% and 10.0% beads were able to induce a higher rate of apoptosis in the embedded cancerous cells when compared to the control groups. The 0.1% TA beads were able to function as a viable scaffold for the duration of the 7 day study while the 1.0% TA beads were initially able to allow preadipocyte cell attachment and growth but after 4 days, the number of viable preadipocyte cells attached to the beads greatly decreased. This study was then repeated using primary cells and the same results were seen. The results of these studies showed that the ideal TA cross-linking concentration was not found. The 0.1% TA beads do not have a high enough concentration to induce apoptosis of cancerous cells while the 1.0% TA beads was too high of a concentration to allow for proper preadipocyte attachment and proliferation. Further studies of concentrations between these two end points is needed.

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Engineering Commons

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