Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Surgery

Supervisor

DeLyzer, Tanya

2nd Supervisor

Turley, Eva

3rd Supervisor

Wong, Eugene

Abstract

Capsular contracture is a common complication of breast implant reconstructive surgery, which can be particularly devastating in the setting of post-mastectomy radiation. The objective of this thesis was to evaluate the effect of RHAMM function-blocking peptide mimetic NP-110 on a novel rodent model for radiation-induced capsular contracture. The model consisted of female rats who underwent surgery to place a 2cc silicone implant under the right fourth mammary fat pad. Animals received local injection of 100ug of NP-110 or scrambled control peptide followed by 26Gy of targeted ionizing radiation. Clinically, NP-110 treated animals showed decreased post-radiation fibrotic change. Masson’s trichrome and Picrosirius red stain showed significantly decreased collagen deposition and bundling in the NP-110 group (p

Summary for Lay Audience

Breast reconstruction is an important part of the patients’ breast cancer journey, that has been shown to improve their quality of life. Most commonly, a new breast can be created with the use of silicone implants. Whenever an implant is placed scar tissue forms around the implant. However, in some cases the scar becomes too tight or thick causing disfigurement and making the breast feel hard and sometimes painful. This is especially common when patients have to undergo radiation therapy as part of their breast cancer treatment, and it can be a difficult problem to treat, commonly requiring multiple surgeries and overall less optimal results.

For this study, we used rats as a test subject to better understand the process that leads to excessive scar around an implant after radiation. A total of 14 rats had surgery to place a mini custom implant that mimics the ones used in humans under the rats’ breast tissue. Four weeks after surgery half the rats were given an injection of an experimental agent, which is known to block a pathway that leads to scaring. The other half were given an injection of an inactive version of the agent. All the animals then received radiation targeted to the breast tissue and implant.

After radiation, we monitored the rats and inspected the implants for four weeks. After four weeks we collected the implant and surrounding scar tissue to do special tests to measure the amount of scar around the implants. The rats that were treated with the active agent had less collagen in their scars under the microscope using special stains compared to the rats treated with the inactive agent.

Overall, this thesis uses a rat model to learn more about how excessive scarring around an implant happens after radiation. We used an active agent that targets a special pathway, and when this pathway is interrupted, we saw decreased scar around the implant. Therefore, this path may be important in causing the excess scar. There is still more to learn, but this research is a step forward in finding new treatments for this difficult problem.

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