Biomedical Engineering and Bioengineering 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 …

Characterization Of Tissue-Specific Matrix-Derived Bioscaffolds For Nucleus Pulposus Cell Culture, Marco A. Herrera Quijano

Electronic Thesis and Dissertation Repository

Bioscaffolds derived from the extracellular matrix (ECM) have shown the capacity to promote regeneration by providing tissue-specific biological instructive cues that can enhance cell survival and direct lineage-specific differentiation. This study focused on the development and characterization of two-dimensional (2-D) and three-dimensional (3-D) cell culture platforms incorporating decellularized nucleus pulposus (DNP). First, a novel detergent-free protocol was developed for decellularizing bovine NP tissues that was effective at removing cellular content while preserving key ECM constituents including collagens and glycosaminoglycans. Culture studies showed that 2-D coatings derived from the DNP could support cell attachment but did not maintain or rescue the …

Development Of Water-Soluble Polyesters For Tissue Engineering Applications, Trent Gordon

Electronic Thesis and Dissertation Repository

The development of tunable polymers has become increasingly important for both tissue engineering and drug delivery. This thesis investigates the development of water-soluble polyesters that contain both natural and synthetic components. These polymers offer tunable chemical structures, as well as functional groups for the conjugation of crosslinking moieties or cell signaling molecules. The first series of polymers was synthesized from poly(ethylene glycol) (PEG) and aspartic acid (Asp) via a titanium catalyzed transesterification method to provide polymers with molar masses of 12 kg/mol. After deprotection, the pendent functional groups of Asp were reacted with methacrylic, maleic, and itaconic anhydride to introduce …

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. …

Fabrication And Characterization Of Collagen-Polypyrrole Constructs Using Direct-Ink Write Additive Manufacturing, Rooshan Arshad

Electronic Thesis and Dissertation Repository

Current efforts in the tissue engineering field are being directed towards the creation of platforms which will facilitate in instructing cells towards biologically relevant outcomes such as stem cell differentiation and disease pathophysiology. Traditional fabrication methods serve as a limiting factor for the production of such platforms as they lack feature and geometric complexity. Additive Manufacturing (AM) offers advantage over said methods by affording designers creative freedom and great control over printed constructs. Such constructs can then be used to create appropriate models for study- ing a plethora of tissues and structures. An AM methodology for Direct-Ink Write (DIW) printing …

Preparation And Characterization Of Electrospun Rgo-Poly(Ester Amide) Tissue Engineering Scaffolds, Hilary Stone

Electronic Thesis and Dissertation Repository

Tissue engineering scaffolds should support tissue maturation through exposure to biologically relevant stimuli and through successful cell infiltration. External electrical stimulation is particularly relevant for cardiac and neural applications, and requires conductive scaffolds to propagate electrical signals; cell infiltration is only possible with scaffolds that have sufficient porosity. The aim of this study was to impart conductivity and increased porosity of electrospun poly(ester amide) (PEA) scaffolds. Reduced graphene oxide (rGO) was incorporated into blend PEA and coaxial PEA-chitosan fibrous scaffolds, which increased scaffold conductivity and supported cardiac differentiation. The novel combination of ultrasonication and leaching of a sacrificial polymer was …

Syngenic Adipose-Derived Stem/Stromal Cells Delivered In Decellularized Adipose Tissue Scaffolds Enhance In Vivo Tissue Regeneration Through Host Cell Recruitment, Kevin P. Robb

Electronic Thesis and Dissertation Repository

Decellularized adipose tissue (DAT) represents a promising adipogenic bioscaffold for applications in soft tissue augmentation or reconstruction. With the goal of investigating the role of syngeneic donor adipose-derived stem/stromal cells (ASCs) and host myeloid cells during in vivo adipose tissue regeneration, transgenic reporter mouse strains were used to track these cell populations within ASC-seeded and unseeded DAT scaffolds. Donor ASCs were obtained from dsRed transgenic mice. These cells were shown to express characteristic cell surface markers, and multilineage differentiation capacity was confirmed. To facilitate cell tracking, DAT scaffolds were subcutaneously implanted into MacGreen mice in which myeloid cells express enhanced …

Functional Co-Substituted Poly[(Amino Acid Ester)Phosphazene] Biomaterials, Amanda L. Baillargeon

Electronic Thesis and Dissertation Repository

The development of new and improved biomaterials is essential for tissue engineering and regenerative medicine applications. Amino acid-based polyphosphazenes are being explored as scaffold materials for tissue engineering applications due to their non-toxic degradation products and tunable material properties. This work focuses on the synthesis of non-functional and novel functional poly[(amino acid ester)phosphazene]s using a facile method of thermal ring opening polymerization followed by one-pot room temperature substitution. The family of polyphosphazenes developed in this work is based on L-alanine (PNEAs), L-phenylalanine (PNEFs), and L-methionine (PNEMs) with L-glutamic acid imparting the functionality. Characterization of these materials demonstrated that the one-pot …

Electrospinning Of Core-Shell Collagen Nanofibers, Ying Li

Electronic Thesis and Dissertation Repository

In tissue engineering, the scaffold plays a critical role in guiding and supporting cells to function and grow optimally. The electrospun nanofibrous scaffold can serve as a near ideal substrate for tissue engineering because it has high surface area and the three-dimensional interconnected porous network can enhance cell attachment and proliferation. Core-shell nanofibrous scaffolds produced with coaxial electrospinning allow bioactive molecule encapsulation to improve cell adhesion, mediate and promote the proper signaling among the cells for their functioning and growth. In the current study, core-shell collagen nanofibers were fabricated via coaxial electrospinning with horizontal and vertical configurations. Core-shell nanofibers with …

Sol-Gel Derived Biodegradable And Bioactive Organic-Inorganic Hybrid Biomaterials For Bone Tissue Engineering, Bedilu A. Allo

Electronic Thesis and Dissertation Repository

Treatments of bone injuries and defects have been largely centered on replacing the lost bone with tissues of allogeneic or xenogeneic sources as well as synthetic bone substitutes, which in all lead to limited degree of structural and functional recovery. As a result, tissue engineering has emerged as a viable technology to regenerate the structures and therefore recover the functions of bone tissue rather than replacement alone. Hence, the current strategies of bone tissue engineering and regeneration rely on bioactive scaffolds to mimic the natural extracellular matrix (ECM) as templates onto which cells attach, multiply, migrate and function.

In this …

Co-Culture Of Smooth Muscle Cells And Endothelial Cells On Porous 3d Polyurethane Scaffolds For Vascular Tissue Engineering, Aparna Bhattacharyya

Electronic Thesis and Dissertation Repository

One of the challenges in the designing of clinically-relevant vascular substitutes is our lack of understanding on how vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) interact in the graft. The aim of this study was to examine the factors that play a role in VSMC and VEC interaction in 3D co-culture. Highly porous 3D poly(carbonate urethane) scaffolds were fabricated using a solvent casting and particulate leaching method. VSMCs and VECs were co-cultured for 48 hours. Immunofluorescence staining showed that VSMCs readily attached to the scaffold and formed dense confluent layers which facilitated the organization of VECs of …