Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Surgery

Supervisor

Eva Turley

2nd Supervisor

Arjang Yazdani

Joint Supervisor

Abstract

Radiofibrosis of the breast makes satisfactory breast tissue reconstruction challenging and is associated with complications. Autologous fat grafting can improve surgical outcomes but fat retention is variable. We developed RHAMM peptide mimetics (NPI-110) that decrease tissue fibrosis and increase mammary fat pad adipogenesis by promoting the differentiation of mesenchymal progenitor cells into adipocytes. We tested the efficacy of NPI-110 in a rat model of radiation-induced mammary fat pad fibrosis. Effects of radiation and NPI-110 were quantified by visible skin changes, fat pad volume estimates using high frequency ultrasound, mRNA expression of genes involved in fibrosis (Collagen-1:Collagen-1, TGFß1) and adipogenesis (PPARγ, adiponectin and perilipin) using qPCR, and collagen fibril deposition using picrosirius red staining. NPI-110 significantly reduced skin inflammation and radiofibrosis, the latter assessed by collagen fibril deposition, and increased mRNA expression of adipogenic markers. Results from this study will aid in creating a micro-environment that optimizes fat transplantation success.


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