Engineering Commons^™

Bioactive And Electrically Conductive Nanocomposite Bone Biomaterials, Rebeca A. Arambula-Maldonado

Electronic Thesis and Dissertation Repository

Electrically conductive carbon-based materials are emerging as potential biomaterials for bone tissue engineering. Their incorporation into organic-inorganic nanocomposites mimics the structural composition and electrically conductive nature of bone.

The aim of this research was to design bone biomaterials from gelatin-based polymers, tertiary bioactive glasses (BG) via a sol-gel method, and multiwall carbon nanotubes (MWCNT). The incorporation of calcium into organic-inorganic nanocomposites plays an essential role in the development of bioactive bone biomaterials. Calcium chloride and calcium ethoxide were investigated as calcium sources in gelatin-BG-MWCNT nanocomposites. The resulting surface elemental distribution was homogeneous, but the swelling, degradation and porosity properties of …

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 …

Conducting Polypyrrole Hydrogel Biomaterials For Drug Delivery And Cartilage Tissue Regeneration, Iryna Liubchak

Electronic Thesis and Dissertation Repository

Articular cartilage tissue has limited capacity for self-regeneration leading to challenges in the treatment of joint injuries and diseases such as osteoarthritis. The tissue engineering approach combines biomaterials, cells and bioactive molecules to provide a long-term and stable cartilage repair. In the following work, electroactive polymer polypyrrole~(PPy) was incorporated into the synthetic hydrogel to enhance the mechanical properties of the material for cartilage applications. PPy was loaded with drug compound and the \emph{on demand} drug release was demonstrated. The composite PPy hydrogel was 3D printed using stereolithography to create a porous tissue engineering scaffold. Biocompatibility and cell adhesion to the …

Motion And Crosslinked Polyethylene Wear In Reverse Total Shoulder Arthroplasty, Christopher Millward

Electronic Thesis and Dissertation Repository

The reverse total shoulder arthroplasty (RTSA) has quickly grown to become the most commonly used shoulder arthroplasty design; however, reports have shown evidence of RTSA failures related to polyethylene wear and damage. Therefore, the present work investigated the wear of crosslinked polyethylene (XLPE) in environments similar to that of an in vivo RTSA. Additionally, a computational model was developed based on a previous study of the shoulder motions obtained from a selection of typical patients with RTSA. This model quantified the amount of glenohumeral motion that an RTSA may be subjected to in vivo and provided an approximate value for …

Development Of Brain-Derived Bioscaffolds For Neural Progenitor Cell Culture And Delivery, Julia Terek

Electronic Thesis and Dissertation Repository

The use of brain extracellular matrix (ECM) as a biomaterial has the potential to promote neural tissue regeneration by providing cell-instructive cues that direct survival, proliferation, and differentiation. This study developed a novel detergent-free decellularization protocol that effectively reduced cellular content while preserving key ECM components in porcine and rat brains. The resulting decellularized brain tissue (DBT) was incorporated into microcarriers to assess its effects on the growth, phenotype and neurotrophic factor gene expression of rat brain-derived progenitor cells cultured within spinner flask bioreactors, using purified collagen microcarriers as a control. Both types of microcarriers supported cell expansion and survival, …

Sol-Gel Derived Bioceramic Poly(Diethyl Fumarate – Co – Triethoxyvinylsilane) Composite, Aref Sleiman

Electronic Thesis and Dissertation Repository

Synthetic bone graft materials have become an increasingly popular choice for bone augmentation. Ceramic-based and polymer-based bone graft materials constitute the two main classes of synthetic bone graft materials. This study investigated the synthesis of novel bioactive composites for their potential use as bone graft biomaterials. Poly(diethyl fumarate-co-triethoxyvinylsilane)/bioceramic class II organic/inorganic hybrid biomaterials were synthesized via a sol gel process. These biomaterials were then reacted with an ammonium phosphate solution to prepare their respective composites. For the first time, we successfully synthesized sol-gel derived bioceramic poly(diethyl fumarate-co-triethoxyvinylsilane) composites. In vitro bioactivity evaluation of poly(diethyl fumarate-co-triethoxyvinylsilane)/bioceramic composites in simulated body fluid …

Organic-Inorganic Hybrid Biomaterials For Bone Tissue Engineering And Drug Delivery, Neda Aslankoohi

Electronic Thesis and Dissertation Repository

Bone biomaterials prepared from a combination of biodegradable polymers and bioactive glasses offer several advantages, including favorable cell interactions, selective gene expression, and delivery of biomolecules. Furthermore, the interaction of the organic and inorganic phases at the molecular level results in a single-phase hybrid material possessing synergistic properties.

This research aimed to design bone biomaterials from α-amino acid-based poly(ester amide) (PEA) and tertiary bioactive glasses using a sol-gel process. Since incorporating calcium into the bioactive glass network is challenging at sol-gel reaction temperatures, calcium ethoxide and calcium chloride were studied as precursors, and the optimum reaction conditions were identified. Mesoporous …

Biomaterial For Cervical Intervertebral Disc Prosthesis, Helium Mak

Electronic Thesis and Dissertation Repository

Recent long-term follow-up studies have shown that the cervical disc arthroplasty treatment have potentials in developing surrounding heterotopic ossification (HO). While its cause requires further investigation, this thesis has hypothesized that it may be the result of the continual remodeling of the injured vertebrae caused by the prostheses with smaller footprints introducing abnormal stresses. The research objective of this thesis is to develop a new prosthesis material that can be molded into any form conforming to the size and shape of the end-plates of the affected patient vertebrae. For prototype development, a composite material consisting of 10wt% polyvinyl alcohol cryogel …

Development Of Multifunctional Drug Delivery Systems For Locoregional Therapy, Xinyi Li

Electronic Thesis and Dissertation Repository

Locoregional treatment is the specific delivery of therapeutics to their desired sites of action with minimized systemic adverse effects. In this approach, drug is administered through topical instillation, inhalation, intra-lesional or intra-arterial injection. Decades of experience in locoregional treatment have delivered meaningful benefits to patients with localized diseases (e.g., osteoarthritis, ocular disorders and liver cancers). However, improvements are required for this type of treatment to be more effective. For transarterial chemoembolization (TACE) therapy of hepatocellular carcinoma (HCC), the most current approaches do not allow repeat treatment as the drug delivery vehicle is not degradable. In addition, image contrast agents for …

3d Printed Polypyrrole Scaffolds For Ph Dependent Drug Delivery With Applications In Bone Regeneration, Matthew T. Lawrence

Electronic Thesis and Dissertation Repository

Areas of large bone loss are typically healed using autologous bone grafts, seen as the gold standard of care. These materials have a complication rate of 10–40% during harvesting and are limited by the quantity available; therefore the use of 3D printed polymer scaffolds as bone graft alternatives are proposed. Polypyrrole (PPy) is a biocompatible electroactive polymer that has metal-like electrical properties that can be harnessed to hold and release charged drug molecules, triggered by a change in pH. pH fluctuations are seen inside the human body in areas of bone regrowth, which would act as the triggering mechanism for …

Catechol-Containing Copolymers As An Active Ingredient For Denture Adhesives, Vincent Ying Wun Kong

Electronic Thesis and Dissertation Repository

Moisture inside the mouth adds challenge to making denture adhesives formulations. Some formulations have zinc to enhance adhesion on wet skin despite knowing the health hazards. Inspired by mussel foot proteins’ catechol unit’s strong underwater adhesion, nine catechol-containing copolymers (P1A-P3C) were synthesized by free radical polymerization of 3,4-dimethoxystyrene (3,4- DMS) with different styrene derivatives followed by deprotection. P1A-P3C were used to make Fn(P)-C-PBS denture adhesive formulations which had suitable shear stresses around ≥ 5 kPa satisfying ISO 10873. In-situ NMR studies of free radical polymerization of 3,4 - DMS and styrene derivatives allowed computation of their reactivity ratios showing all …

Extracellular Matrix-Derived Microcarriers As 3-D Cell Culture Platforms, Anna Kornmuller

Electronic Thesis and Dissertation Repository

Recognizing the cell-instructive capacity of tissue-specific extracellular matrix (ECM) to direct cell attachment, proliferation and differentiation, there is a need for the development of in vitro cell culture models that reflect the complexity of the ECM to improve stem/progenitor cell expansion and lineage-commitment. This thesis focused on the development and characterization of ECM-derived microcarriers for the in vitro dynamic culture and expansion of stromal cells for cell therapy and tissue engineering applications.

To develop novel platforms for use in dynamic culture systems, initial work focused on applying electrospraying techniques to fabricate microcarriers from decellularized dermal tissue (DDT) and decellularized myocardial …

Fibrin-Based Engineered Vascular Tissues As Platforms For Cellular Studies And Disease Modeling, Khalil Dayekh

Electronic Thesis and Dissertation Repository

Vascular tissue engineering (VTE) is an emerging alternative therapeutic intervention strategy to treat diseases such as atherosclerosis. While the ultimate goal of VTE is designing tissues to serve as graft substitutes, they can also serve as powerful tools to study tissue and disease development and drug discovery.

In this work, engineered vascular tissues from fibrin gel, mouse embryonic multipotent progenitor cell line (10T1/2 cells), and rat embryonic thoracic artery smooth muscle cells (A-10 cells) were used as models to study the Notch signaling pathway and vascular calcification. The 10T1/2 cells were successfully differentiated into vascular smooth muscle cells with TGFβ1 …

Development Of Hybrid Coating Materials To Improve The Success Of Titanium Implants, Zach Gouveia

Electronic Thesis and Dissertation Repository

While titanium (Ti) and its alloys have become ubiquitous within implantology as materials to restore or augment the function of human tissues, their success is plagued by complications associated with infection and aseptic implant loosening. These two risks account for the majority of implant failures in the clinic and limit the long-term success of titanium implants in vivo. Therefore, this thesis describes the development of robust multifunctional class II organic-inorganic hybrid coating materials for titanium implants that could be used to effectively target both complications, concurrently. During this master’s work, two different coating systems were examined. First, class II …

Metal Additive Manufacturing For Fixed Dental Prostheses, Mai El Najjar

Electronic Thesis and Dissertation Repository

The use of additive manufacturing (AM) in dentistry has gained momentum in recent years. However, high initial costs and uncertainty surrounding the quality of AM products are considered barriers to their use. This research compared dental substructures fabricated by AM versus conventional casting and milling.

Cobalt-chromium alloy rectangular bars and three-unit bridge substructures were fabricated by AM, casting or milling. Bars manufactured by AM exhibited superior flexural strength, shear bond strength of porcelain coating, and Vickers hardness. Bridge substructures fabricated by AM showed similar flexural stiffness to cast, similar flexural loads at failure to milled and cast, and overall accuracy …

3d Culture Strategies For The Dynamic Expansion And Preconditioning Of Adipose-Derived Stromal Cells On Decellularized Adipose Tissue Bioscaffolds, Tim Tian Han

Electronic Thesis and Dissertation Repository

Adipose tissue engineering holds promise for the development of therapeutic strategies for subcutaneous adipose tissue regeneration to treat defects resulting from congenital birth defects, invasive surgical procedures and traumatic injuries. Decellularized adipose tissue (DAT) scaffolds represent a potential off-the-shelf tissue substitute for volume augmentation. Seeding the DAT with adipose-derived stromal cells (ASCs) has been shown to enhance adipose tissue regeneration in immunocompetent animals in vivo. Although promising, this strategy is limited by low cell attachment on the DAT. As such, this thesis focused on the development of bioreactor strategies to enhance the capacity of human ASCs to stimulate angiogenesis …

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 …

Preparation Of Intra-Articular Drug Delivery Systems For The Treatment Of Osteoarthritis, Ian Villamagna

Electronic Thesis and Dissertation Repository

Osteoarthritis (OA) is a degenerative disease of the articular joints that affects over 240 million people globally. Despite its overwhelming prevalence, there is no disease modifying agent currently available to treat the disease, and many treatment options remain palliative in nature. Potentially effective treatments for OA are limited by probable systemic side effects. Intra-articular drug delivery systems present a new opportunity for the treatment of OA; encapsulated therapeutics can be injected directly into the joint, at the area of injury, thereby bypassing systemic administration and diminishing the chance for side effects. This thesis describes the research and development of novel …

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. …

Bioluminescence Resonance Energy Transfer (Bret) - Based Nanostructured Biosensor For Detection Of Glucose, Eugene Hwang

Electronic Thesis and Dissertation Repository

Bioluminescence resonance energy transfer (BRET) is a distance dependent, non-radiative energy transfer, which uses a bioluminescent protein to excite an acceptor through resonance energy transfer. In this thesis, BRET technology is incorporated into a sensor comprised of a recombinant protein and quantum dots. The recombinant protein, which includes the bioluminescent protein, Renilla luciferase (Rluc), is used as the donor molecule and cadmium tellurium quantum dots as the acceptor molecules. Separating the donor-acceptor pair is a recombinant protein, glucose binding protein, which changes conformation upon binding glucose and brings the pair closer together, thus allowing BRET to occur. Optimization of the …

High-Throughput Fabrication Of Drug-Loaded Core-Shell Tablets With Adjustable Release Profiles From Surface-Erodible And Photocrosslinkable Polyanhydrides, Armin Geraili Nejadfomeshi

Electronic Thesis and Dissertation Repository

Controlled-release tablets enhance the effectiveness of therapies for various clinical conditions. Photocrosslinkable polyanhydrides that undergo surface erosion were recently introduced as suitable materials for manufacturing tablets with tunable release profiles. However, their erosion behavior has not been comprehensively studied. In this thesis, the erosion kinetics of photocrosslinkable polyanhydrides was studied by exploring the impact of different parameters (the polymer composition and geometry, as well as the temperature, pH, and shaking rate of the solution during the in vitro experiments) on their mass loss profiles, followed by a release kinetic model fitting. The results indicate that the temperature was the only …

Design Of Cell-Instructive Biomaterial Scaffolds For Intervertebral Disc Regeneration, Nadia Sharma

Electronic Thesis and Dissertation Repository

Biomaterials-based therapies targeting the nucleus pulposus (NP) have the potential to promote regeneration and restore mechanical function to the intervertebral disc. This study developed composite hydrogels incorporating decellularized NP (DNP) and assessed its effects on viability, retention and differentiation of U-CH1 cells, an NP progenitor-like cell line. A minimal protocol was developed to decellularize bovine NP that reduced nuclear content while preserving key extracellular matrix components predicted to be favourable for bioactivity. The resulting DNP demonstrated cell-instructive effects, supporting U-CH1 viability and retention within the hydrogels, and promoted the differentiation of the progenitor-like cells towards an NP-like phenotype. These studies …

Formation Of A Vascular Regenerative Microenvironment Within Implantable Human Decellularized Adipose Tissue Bioscaffolds, Christopher Leclerc

Electronic Thesis and Dissertation Repository

Cellular therapies targeted at stimulating therapeutic angiogenesis in individuals with critical limb ischemia (CLI) have been under intense investigation. Hematopoietic progenitor cells (HPC) derived from umbilical cord blood have been previously shown to support limb revascularization in animal models of CLI, despite limited cell survival at the site of ischemia. This study attempted to improve HPC survival after transplantation and prolong pro-angiogenic function using human decellularized adipose tissue (hDAT) as a novel cell delivery platform. Compared to HPC conventionally grown on tissue-cultured plastic, hDAT scaffolds were shown to promote viability and proliferation of seeded HPC, and had cell- instructive effects …

Scaffold Design Considerations For Soft Tissue Regeneration, Madeleine M. Di Gregorio

Electronic Thesis and Dissertation Repository

Tissue engineering has emerged as a promising strategy for the replacement of degenerating or damaged tissues in vivo. Also known as regenerative medicine, integral to this therapeutic strategy is biomimetic scaffolds and the biomaterial structural components used to form them. In this study, three different biomaterial scaffolds for tissue engineering applications were fabricated: three-dimensional reverse embedded collagen scaffolds, polymer fusion printed polycaprolactone (PCL) scaffolds, and electrospun gelatin scaffolds. Three-dimensional collagen and PCL scaffolds promoted human adipose-derived stem/stromal cell (ASC) spreading, proliferation, and fibronectin deposition in vitro. Secondly, this study investigated the efficacy of exogenous galectin-3 delivery as a …

A Ph-Sensitive Delivery System For The Prevention Of Dental Caries Using Salivary Proteins, Yi Zhu

Electronic Thesis and Dissertation Repository

Dental caries remains one of the most common chronic diseases worldwide. Salivary proteins such as histatins have demonstrated biological functions directly related to tooth homeostasis and prevention of dental caries. However, histatins are susceptible to the high proteolytic activities in the oral environment. Therefore, pH-sensitive chitosan nanoparticles (CNs) have been proposed as potential carriers to target major oral diseases that occur under acidic conditions (e.g. dental caries and dental erosion). Four different types of chitosan polymers were investigated and the optimized CNs successfully loaded histatin 3 and released it selectively under acidic conditions. Through loading the survival time of histatin …

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 …

Tissue Equivalent Gellan Gum Gel Materials For Clinical Mri And Radiation Dosimetry, Pawel Brzozowski

Electronic Thesis and Dissertation Repository

Hydrogels contain high amount of water allowing their use as surrogates to human tissues with specific properties that can be tuned by additives. Gellan gum is a gel-forming material of interest and is a replacement for other common gelling agent with limited use as a tissue phantom. Therefore, this thesis examines the application of gellan gum gels as a novel magnetic resonance imaging (MRI) phantom with a design of experiments model to obtain tunable properties. The analysis was extended to include mechanical and electrical properties with a separate design of experiment. Gels doped with synthesized superparamagnetic iron oxide nanoparticles (SPIONs) …

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 …

Development Of In Situ Forming Hydrogels For Intra-Articular Drug Delivery, Andy Prince

Electronic Thesis and Dissertation Repository

Hydrogels are 3-dimensional crosslinked polymer networks that can absorb significant amounts of water. The physical properties associated with hydrogels affords them resemblance to biological tissues making them good candidates for biomedical applications. Many pharmaceuticals, specifically non-steroidal anti-inflammatory drugs (NSAIDs), have poor aqueous solubility, which limits their bioavailability and efficacy. People suffering from chronic osteoarthritis (OA) are required to frequently take large doses to mitigate pain, which can lead to serious side effects. Hydrogels are good strategies to deliver NSAIDs via articular injection because they can form solid gels in situ. This thesis describes the synthesis, formulation, mechanical testing, in …

Apply Dry Powder On Drug Loading And Enteric Coating Of Esomeprazole Magnesium Trihydrate Beads And Capsules, Xiaojing Ge

Electronic Thesis and Dissertation Repository

Esomeprazole magnesium tri-hydrate (EMT) is a proton pump inhibitor, used for the treatment of gastric and duodenum ulcers. It is currently the best choice for the treatment of acid-related diseases, but it is extremely unstable in gastric acid and sensitive to wet, heat, light. It also will react with the enteric coating material used in this study. So enteric coating and sub coating is needed.

This study offers a new approach, dry powder coating technology, to achieve drug loading and enteric coating of EMT beads and capsules. Dry powder coating, a new type of solvent-less coating technology, can address most …