Project 456427

While often regarded negatively, the adipose tissue (fat) layer within the skin plays a critical role in defining the natural contours of the human body. Following damage or injury, these tissues have a limited capacity for repair, contributing to scar tissue formation that can cause deformity, limit mobility, and profoundly impact self-image and quality of life. This research addresses the unmet clinical need for new approaches that enable the stable and predictable regeneration of healthy subcutaneous soft tissues for applications including breast reconstruction following tumour removal, the correction of congenital birth defects, and soft tissue repair following trauma or burns. In previous studies, our team has designed novel protein-based scaffolds derived from human fat discarded as surgical waste that can be applied as off-the-shelf tissue substitutes that naturally promote the regeneration of healthy host-derived soft tissues. Further, we have shown that seeding these scaffolds with adult stem cells sourced from fat, termed adipose-derived stromal cells (ASCs), can augment the regenerative response in pre-clinical models. Building from this promising foundation, in the current study our interdisciplinary research team will develop novel approaches to augment the capacity of human ASCs delivered within the scaffolds to stimulate stable soft tissue regeneration. More specifically, we will develop customized bioreactor systems and new scaffold formats that enable the localized delivery of a high-density of pro-regenerative ASCs to guide soft tissue replacement. Using advanced cell culture systems and pre-clinical mouse models, we will explore the cellular response in depth to develop a critically-needed understanding of the biological mechanisms of ASC-mediated regeneration and advance towards the clinical translation of our innovative therapies for applications in reconstructive surgery.