Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Engineering Science

Program

Biomedical Engineering

Collaborative Specialization

Musculoskeletal Health Research

Supervisor

Flynn, Lauren E.

Abstract

Decellularized adipose tissue (DAT) bioscaffolds are a promising platform for the delivery of pro-regenerative cell populations with the goal of promoting adipose tissue regeneration. The current study investigated the effects of seeding DAT bioscaffolds with syngeneic bone marrow-derived macrophages and/or adipose-derived stromal cells (ASCs) on in vivo soft tissue regeneration. Methods were established to derive the macrophages from MacGreen mice, which were dynamically seeded onto the DAT scaffolds alone or in combination with ASCs. Seeded and unseeded scaffolds were implanted subcutaneously into C57Bl/6 mice. At 2 and 4 weeks, cell infiltration, angiogenesis, and adipogenesis were analyzed through histology and immunohistochemistry. Substantial variability was observed, but higher blood vessel densities and greater CD31+ cell recruitment was observed in the implants that were greatly infiltrated with cells. A diverse, infiltrating macrophage population was identified in all implants, with quantitatively higher iNOS expression in the scaffolds that showed greater levels of cell infiltration.

Summary for Lay Audience

Adipose or fat tissue has a limited ability to repair and regenerate itself following trauma, burns, surgical removal of tumors, or birth defects. The process of fat regeneration is dependent on 1) coordinating multiple types of cells in the body to migrate, 2) forming new blood vessels, 3) and cells achieving a more pro-regenerative state to support new fat cell formation. There is an increasing interest in delivering therapeutic cells, such as adipose-derived stromal cells (ASCs) and immune cells called macrophages, which have been shown to stimulate the biological process of fat tissue regeneration. Also, 3-D porous decellularized adipose tissue (DAT) implants have been previously developed as a promising platform to deliver therapeutic cells into areas of the body with large defects. The present thesis focused on using DAT implants to deliver both ASCs and macrophages into mice. Initially, the DAT implants were found to support macrophage and ASC attachment. After DAT implants were delivered into mice either alone or with macrophages, ASCs, or macrophages + ASCs, different levels of cell migration, as well as blood vessel and fat formation were observed within the implants in all groups after 2 and 4 weeks. In general, the implants that had greater levels of cells migrating into them also had more blood vessels being formed. Also, different types of macrophages were observed within the DAT implants in all groups at both time points, all of which may be playing an active role in regeneration. Overall, this study showcases the intricate and complex relationships between regeneration, cell recruitment, blood vessel formation, and inflammation.

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