Engineering Commons^™

Development Of A Cell-Based Regenerative Strategy To Modulate Angiogenesis And Inflammation In Ischemic Muscle, Fiona E. Serack

Electronic Thesis and Dissertation Repository

The delivery of human adipose-derived stromal cells (hASCs) to ischemic tissues represents a promising strategy to promote vascular regeneration for patients with critical limb ischemia (CLI). This thesis focused on the evaluation of hydrogels to enhance the retention and pro-angiogenic capacity of hASCs following delivery in vivo. Additionally, priming strategies to augment the paracrine function of hASCs were developed and assessed.

Recognizing the importance of endogenous macrophages in the pro-regenerative function of hASCs, delivery using a previously-developed hydrogel system, composed of peptide-functionalized methacrylated glycol chitosan (MGC-RGD) and a copolymer of poly(ethylene glycol) and poly(trimethylene carbonate) (PEG(PTMC-A)₂), was …

Investigation Of Dynamic Culture On Matrix-Derived Microcarriers As A Strategy To Modulate The Pro-Regenerative Phenotype Of Human Adipose-Derived Stromal Cells, Mckenna R. Tosh

Electronic Thesis and Dissertation Repository

Pre-conditioning of adipose-derived stromal cells (ASCs) by tuning the cellular microenvironment during expansion has the potential to modulate their pro-regenerative functionality. The current study investigated the effects of microcarrier composition (decellularized adipose tissue versus collagen), oxygen tension (2% versus ~20% O₂) and stirring rate (static, 20, 40 rpm) on human ASCs cultured within spinner flask bioreactors. Dynamic culturing under 20% O₂ resulted in more consistent cell growth on both microcarrier substrates, leading to increases in microcarrier contraction and stiffness. Culturing on the microcarriers modulated the hASC immunophenotype, with varying CD90 and CD26 expression levels observed under the …

Extracellular Matrix-Derived Modular Bioscaffolds For Soft Connective Tissue Regeneration, Pascal Morissette Martin

Electronic Thesis and Dissertation Repository

Human decellularized adipose tissue (DAT) represents a promising extracellular matrix (ECM) source for the development of biomaterials, with its properties conductive of angiogenesis, adipogenesis, and scaffold remodelling. This thesis sought to provide new fundamental insight into the design of ECM-derived bioscaffolds by developing novel modular biomaterials for soft connective tissue regeneration and by studying the effects of ECM composition on cell function and fate.

Initial studies explored the effects of ECM composition of pre-assembled bead foams derived from DAT or commercially-sourced bovine collagen (COL) on human wound edge dermal fibroblasts (weDFs) sourced from chronic wounds. In vitro testing under conditions …

The Co-Delivery Of Syngeneic Adipose-Derived Stromal Cells And Macrophages On Decellularized Adipose Tissue Bioscaffolds For In Vivo Soft Tissue Regeneration, Hisham A. Kamoun

Electronic Thesis and Dissertation Repository

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. …

Design Of Tissue-Specific Cellular Microenvironments For Adipose-Derived Stromal Cell Culture And Delivery, Arthi Shridhar

Electronic Thesis and Dissertation Repository

The development of in vitro cell culture models that investigate tissue-specific effects of the extracellular matrix (ECM) on stem/progenitor cell lineage-commitment can contribute towards the design of improved cell delivery strategies. This thesis developed processing methods that conserved ECM bioactivity to generate well-characterized 2- and 3-D culture platforms that facilitated the evaluation of ECM composition on the adipogenic and osteogenic differentiation of human adipose-derived stromal cells (ASCs). Initial work compared α-amylase and pepsin digestion as methods to fabricate ECM coatings. The effects of enzyme processing and ECM composition were explored using human decellularized adipose tissue (DAT) and bovine tendon collagen …