A Tissue Engineered Nipple and Areola Complex

There are more than 2.8 million breast cancer survivors in the United States, many of who have undergone reconstructive surgery. Approximately 36% of patients with early stage diagnoses and 60% of patients with late stage diagnoses undergo mastectomies. Moreover, immediate breast reconstruction following mastectomies has become more common, significantly increasing at an average rate of 5% per year, from 20.8% in 1998 to 37.8% in 2008. This increasing trend is not surprising as breast reconstruction likely provides psychological benefits for women who undergo mastectomies. There is evidence to suggest that nipple and areola complex (NAC) reconstruction affects psychological wellbeing by enhancing body image and selfesteem, or decreasing the feeling of distress felt by female patients with mastectomies. Due to this, there exists a need for a reproducible and more naturally aesthetic architecture for NAC reconstruction. Current strategies for NAC reconstruction are limited to surgical techniques that create a NAC-like structure from existing local tissue, secondary site grafting, 3D tattooing, or using commercially available acellular dermal matrix sheets, such as Alloderm. Generating a tissue engineered, biocompatible NAC implant, made of decellularized whole NAC, for use in place of surgically created NAC structures is a promising approach to NAC reconstruction following mastectomies. To date, no tissue engineering and cellular therapy strategies have been developed focused on NAC reconstruction. The application of decellularization to the whole, semi-glandular NAC can create a non-immunogenic NAC that retains the microarchitecture and gross structures of a native NAC. This tissue engineering approach to whole NAC structure regeneration allows for the effective removal of cellular material, the retention of the extracellular matrix components and structure, as well as cell adhesion molecules. Once decellularized, NAC scaffolds would be seeded with autologous cells to create a graft that is patient-specific. Preliminary studies have shown, using tissues from a Rhesus Macaque Non- Human Primate animal model, that biologically derived scaffolds were able to be reproducibly isolated with effective removal of nuclear material—less than ≈50ng of 200bp DNA per mg of sample remaining. Through histological analysis of the NAC scaffolds it was shown that the presence of extracellular matrix and adhesion proteins were maintained after the decellularization process. Additionally, bioactivity of the scaffolds were assessed using rhesus bone marrow-derived stem cells for one week, under dynamic cell culture conditions. Herein, a tissue engineered, regenerative medicine approach to reconstruct the nipple and areola complex using a biologically derived scaffold and autologous cell sources is described.