Advanced 3D auxetic biodegradable implant for large volume breast reconstruction - Abstract Breast cancer remains the most prevalent cancer in women worldwide, requiring surgical interventions for tumor removal and subsequent breast reconstruction. The current predominant breast reconstruction using non-biodegradable silicone or saline implants have a high risk of complications, including fibrous capsule formation, pain, deformity, and even implant rupture. While a number of tissue engineering approaches using biodegradable scaffolds have recently emerged as an alternative to address the current challenges, current outcomes have demonstrated limited volume of the regenerated adipose tissue due to a lack of vasculature ingrowth. A novel auxetic architecture with high flexibility, non-linear stiffening behavior, and permeability, was recently developed for large volume soft tissue engineering. The primary hypothesis of this research is that scaling up the geometric design of the auxetic architecture design will further enhance its structural, mechanical, and biological performance, in terms of flexibility, durability, permeability, and tissue regeneration capability for large volume breast reconstruction. In Aim 1, the scaled-up auxetic designs will be characterized in comparison with the original design through in-depth investigations including Finite Element (FE) simulation, µCT analysis, and mechanical testing to demonstrate its biomechanical properties directly comparable to the native adipose tissue. In Aim 2, the biological performance of the scaled-up auxetic designs will be examined in comparison with the original design. This involves assessment of cell viability and functionality of adipose-derived stromal cells (ASCs) in vitro using large volume original and scaled-up auxetic cubes. Finally, dome-shaped auxetic implants, with dimensions of 100 mm bottom diameter and 50 mm height, infilled with hydrogel containing adipose tissue segments, will be implanted into the abdominal cavity of Yucatan swine for 1 month. Adipose tissue regeneration will be assessed through histological and immunochemical analysis.