Biomedical Engineering and Bioengineering Commons^™

Bioadhesive Hydrogel Composite Cell Carrier For The Repair Of The Degenerated Intervertebral Disc, Thomas Richard Christiani

Theses and Dissertations

Lower back pain (LBP) affects the worldwide population and can be attributed to the degeneration of the intervertebral disc (IVD). The IVD is composed of a central nucleus pulposus (NP), a peripheral annulus fibrosus (AF), and adjacent cartilage endplates (CEPs). IVD degeneration is characterized by proteoglycan loss, tissue dehydration, and decreased hydrostatic pressure. In this work, the use of an injectable bioadhesive hydrogel composite for replacement of the degenerated NP was investigated.

Results indicate that the composite exhibits similar mechanical properties to the NP, adheres to AF tissue, and supports encapsulated mesenchymal stem cell (MSC) differentiation toward an NP-like phenotype …

Dendrimer-Based Therapeutic Delivery Vehicle For The Treatment Of Ocular Diseases, Remy C. Cooper

Theses and Dissertations

The treatment of ocular diseases poses a significant challenge to drug delivery design, due to the eye’s complex anatomy, with a semi-permeable blood-ocular barrier and associated immune privilege. To address some of the delivery challenges, polycationic dendrimers are explored as vehicle for the treatment of posterior chamber disease. Dendrimers are a class of polymeric nanoparticles that are highly branched, multivalent and monodisperse, whose three-dimensional globular architecture has given them the nickname of “synthetic proteins”. Dendrimers are synthesized by reacting monomers in a step-wise fashion to produce generationally and radially increasing structures, with core, interior and surface chains that are highly …

Analysis Of Cellular Interactions Within A Collagen Hydrogel, Austin N. Worden

Theses and Dissertations

Evidence has arisen over the past several years that use of a three- dimensional (3D) culture system provides a distinct advantage over two- dimensional (2D) systems when cellular interactions are examined in a more natural environment. Changes in morphology, speed, and directionality of cells tested in both planar and 3D matrices have all demonstrated that using 3D system is advantageous. The changes to the cellular migration patterns were shown to be dependent on several variables within the surrounding substrate including cellular content, physical environment, and the matrix chemical milieu. We have taken advantage of using collagen hydrogels as a 3D …

Acoustofluidics And Soft Materials Interfaces For Biomedical Applications, Frank A. Fencl

Biomedical Engineering ETDs

This dissertation describes fabrication of devices and other tools for biomedical applications through the integration of acoustofluidic systems with bio separation assays, instrumentation components, and soft materials interfaces. For example, we engineer a new class of transparent acoustic flow chambers ideal for optical interrogation. We demonstrate efficacy of these devices by enhancing the signal for high throughput acoustic flow cytometry, capable of robust particle focusing across multiple parallel flowing streams. We also investigate an automated sampling system to determine the parameters of transient particle stream focusing in between sample boluses and air bubbles to model a high throughput, multi-sampling acoustic …

Synthesis And Characterization Of Blue Light Poly(Β-Amino Ester)S, Nicholas John Kohrs

Theses and Dissertations--Biomedical Engineering

Volumetric muscle loss (VML) is a debilitating injury which results in full or partial loss of function. Current clinical options utilize tissue grafts and bracing to restore function. Tissue graft implantation oftentimes leads to serious complications, some of which end in graft rejection and thereby necessitate further surgeries and procedures. Polymeric scaffolds show promise as scaffolding systems due to their mechanical properties and overall degradation profiles. Scaffolds need appropriate mechanical properties, 10-60 kPa modulus, and overall degradation times, five days to two weeks, to initiate tissue regeneration. Poly(β-amino ester)s (PBAE), a class of synthetic polymers, act as a safe biocompatible …

An Injectable Thermosensitive Biodegradable Hydrogel Embedded With Snap Containing Plla Microparticles For Sustained Nitric Oxide (No) Delivery For Wound Healing, Nikhil Mittal

Dissertations, Master's Theses and Master's Reports

After injury, wound healing is a complex sequential cascade of events essential for the proper recovery of the wound without the scar formation. Nitric oxide (NO) is a small, endogenous free-radical gas with antimicrobial, vasodilating and growth factor stimulating properties. NO has wide biomedical application especially in wound healing however, its usability is hindered due its administration problem as it is highly unstable.

In this work, poly (l-lactic acid) microparticles encapsulated with NO donor S-nitroso-N-acetyl-D-penicillamine (SNAP) were prepared using water-in-oil-water double emulsion solvent evaporation method for controlled delivery for NO at the specific site. The NO release from SNAP-PLLA microparticles …

Ultrasonically Responsive Tissue Engineering Scaffolds For The Temporal Control Over Osteo-Inductive Growth Factor Delivery, Catherine Linh

Senior Honors Projects

In 2012, approximately 6.8 million people in the United States were diagnosed with orthopedic injuries or diseases. Over 500,000 people in the United States underwent bone grafting procedures, which cost 2.5 billion dollars per year and can result in complications. Polymer-based grafting scaffolds can facilitate 3D bone tissue growth in a localized, sustained manner. However, bone regeneration requires the orchestration of a sequence of events. Current scaffolds based on degradation and diffusion cannot provide sequential deliveries. We aimed to design a polymer scaffold that can release one payload diffusively at early time points, followed by ultrasonically triggered release of a …

Patient-Derived Hydrogel As A Sacrificial Matrix For Efficient Cell Loading, Shalmli U. Joshi

Honors Scholar Theses

The field of tissue engineering focuses on delivering patient-derived stem cells to the body through the use of degradable biomaterials, such as hydrogels, which are infused into engineered scaffolds. Hydrogels act as templates to support and guide cells towards the regeneration of new tissue. In this study, we introduce a completely intraoperative procedure for obtaining a fibrin hydrogel for tissue engineering applications. In the past, fibrin hydrogel has been commonly formed by combining fibrinogen protein with animal-derived thrombin. Instead, we have developed an automated, and therefore reproducible, protocol to isolate and form fibrin hydrogel without the use of animal-derived thrombin. …

Polysaccharide Fabrication Platforms And Biocompatibility Assessment As Candidate Wound Dressing Materials, Donald C. Aduba Jr., Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Wound dressings are critical for wound care because they provide a physical barrier between the injury site and outside environment, preventing further damage or infection. Wound dressings also manage and even encourage the wound healing process for proper recovery. Polysaccharide biopolymers are slowly becoming popular as modern wound dressings materials because they are naturally derived, highly abundant, inexpensive, absorbent, non-toxic and non-immunogenic. Polysaccharide biopolymers have also been processed into biomimetic platforms that offer a bioactive component in wound dressings that aid the healing process. This review primarily focuses on the fabrication and biocompatibility assessment of polysaccharide materials. Specifically, fabrication platforms …

Modified Pamam Dendrimers In Tunable Drug-Delivery Systems: A Sustained-Release Dendrimer Hydrogel For Anti-Glaucoma Drugs And Surface-Engineered Macrophages As Nanoparticle Carriers For Targeted Anti-Cancer Therapy, Christopher A. Holden

Theses and Dissertations

Two specific drug-delivery applications were sought in this work using polyamidoamine (PAMAM) dendrimers. One drug-delivery system used a novel dendrimer hydrogel (DH) for sustained delivery of anti-glaucoma drugs. In this work, PAMAM G3.0 dendrimers were covalently bonded with poly(ethylene glycol) (PEG­₁₂₀₀₀) molecules which were subsequently acrylated, resulting in photocurable DH conjugates. For pharmacological studies, DH were loaded with a solution of intraocular pressure lowering drugs, brimonidine and timolol maleate, and were characterized for in vitro release and ex vivo transport and uptake. DH formulations were shown to increase the loading of drug molecules, increase transcorneal drug delivery, and …

3d Bioprinting Hydrogel For Tissue Engineering An Ascending Aortic Scaffold, Benjamin Stewart

Electronic Theses and Dissertations

The gold standard in 2016 for thoracic aortic grafts is Dacron^®, polyethylene terephthalate, due to the durability over time, the low immune response elicited and the propensity for endothelialization of the graft lumen over time. These synthetic grafts provide reliable materials that show remarkable long term patency. Despite the acceptable performance of Dacron^® grafts, it is noted that autographs still outperform other types of vascular grafts when available due to recognition of the host's cells and adaptive mechanical properties of a living graft. 3-D bioprinting patient-specific scaffolds for tissue engineering (TE) brings the benefits of non-degrading synthetic …

Design Of Robust Hydrogel Based On Mussel-Inspired Chemistry, Yuan Liu

Dissertations, Master's Theses and Master's Reports

The structure of catechol is found in mussel adhesive proteins and contributed to both wet-resistant adhesion and cohesive curing of these proteins. A synthetic nano-silicate, Laponite was incorporated into catechol-containing hydrogels and the hydrogel network-bound catechol formed strong reversible interfacial interaction with Laponite. The contribution of incorporated catechol-Laponite reversible interfacial interactions to the mechanics of hydrogels constructed by different strategies was studied. In the first strategy, Laponite and catechol were introduced into the double network hydrogel (DN) via the free radical co-polymerization of a catechol-containing monomer, backbone monomer, and crosslinker. The introduction of catechol-Laponite interactions significantly improved the compressive strength …

Development Of Orthogonally Crosslinked Thiol-Ene Hydrogels For Encapsulation Of Pancreatic Beta-Cells, Han Shih

Open Access Dissertations

Type I diabetes mellitus (T1DM) is an autoimmune disease caused by auto-reactive T-cell-mediated destruction of insulin-producing β-cells. Effective encapsulation strategies can protect the transplanted islets from direct attack by host immune cells while maintaining insulin secretion. To achieve this goal, I have developed a hydrogel conformal coating using a visible light-mediated interfacial thiol-ene photopolymerization. Unlike conventional chain-growth visible light polymerizations, no additional cytotoxic co-initiator or co-monomer was required in thiol-ene gelation scheme for rapid gelation. More importantly, islets coated with thiol-ene gel maintained their viability and function in vitro. In addition to microencapsulate β-cells, the second objective of my …

Fabrication And Characterization Of An Extracellular Matrix Hydrogel For Aortic Valve Applications, Brady Culbreth

All Theses

With an estimated 5 million people suffering from valve disease in the United, valve disease is currently the leading cause of cardiovascular disease. Each year, between 80,000 and 85,000 aortic valve replacements are performed in order to treat the stenotic heart valves. Despite this being a worldwide epidemic, the current valve replacement options that are on the market have distinct limitations. Furthermore, a viable alternative does not exist for the patients that are not candidates for the current treatment methods. Our proposed solution to this epidemic is to create a highly viable injectable scaffold that would allow for the minimally …

Design And Production Of A Hydrogel Forming Polypeptide: Engaging High School Students In Protein Design, James K. Deyling

ETD Archive

Bioinks are a class of hydrogel that have the potential to be the ink used in the creation of printed organs, connective tissue, and other important structures within the body. One class of material that may be a suitable bioink hydrogel is elastin-like polypeptides (ELPs), which are synthetic biopolymers inspired by the naturally existing connective tissue elastin. ELPs consist of a repeat pentapeptide sequence (GXGVP)n, where X is any of the 20 naturally existing amino acids other than proline. These biomolecules are capable of exhibiting environmental responsiveness when exposed to certain stimulus such as salt concentration, temperature, and pH, depending …

An Injectable Stem Cell Delivery System For Treatment Of Musculoskeletal Defects, Shirae Leslie

Theses and Dissertations

The goal of this research was to develop a system of injectable hydrogels to deliver stem cells to musculoskeletal defects, thereby allowing cells to remain at the treatment site and secrete soluble factors that will facilitate tissue regeneration. First, production parameters for encapsulating cells in microbeads were determined. This involved investigating the effects of osmolytes on alginate microbead properties, and the effects of alginate microbead cell density, alginate microbead density, and effects of osteogenic media on microencapsulated cells. Although cells remained viable in the microbeads, alginate does not readily degrade in vivo for six months. Therefore, a method to incorporate …

Design And Development Of Two Component Hydrogel Ejector For Three-Dimensional Cell Growth, Thomas Dunkle, Jessica Deschamps, Connie Dam

Honors Scholar Theses

Hydrogels are useful in wound healing, drug delivery, and tissue engineering applications, but the available methods of injecting them quickly and noninvasively are limited. The medical industry does not yet have access to an all-purpose device that can quickly synthesize hydrogels of different shapes and sizes. Many synthesis procedures that have been developed result in the formation of amorphous hydrogels. While generally useful, amorphous hydrogels exhibit limited capability in tissue engineering applications, especially due to their viscous properties. This endeavor aims to modulate the appropriate gelation parameters, optimize the injection process, and create a prototype that allows for the extrusion …

Brown Adipogenesis Of Mouse Embryonic Stem Cells In Alginate Microstrands, Andrea Mannarino Unser

Legacy Theses & Dissertations (2009 - 2024)

The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders. Employing pluripotent stem cells, with an emphasis on directed differentiation, may overcome many issues currently associated with primary fat cell cultures. However, brown adipocytes are difficult to transplant in vivo due to the instability of fat, in terms of necrosis and neovascularization, once injected. Thus, 3D cell culture systems that have the potential to mimic adipogenic microenvironments are needed, not only to advance brown fat implantation, but also to better understand the role of brown adipocytes …

Automating The Process Of Fabricating Uniform-Sized Cell Spheroids For Three-Dimensional Bioprinting, Ganesh Sosale

Theses and Dissertations

Although researchers have been able to print small, simple, and avascular tissues, they have been unsuccessful in creating large, complex and vascularized organs. Printing large and complex three-dimensional tissues or organs involves utilizing a large quantity of cellular spheroids and layer-by-layer addition of spheroids. In this study, an in-house cell spheroid fabrication system was developed to produce cell spheroids with human liver cells (hepG2), human endothelial cells (hEC), human neural stem cells (hNSC), and induced pluripotent stem cells (iPSC). It offers the ability of fabricating uniform-sized spheroids repeatedly, which is essential when large and complex structures need to be produced. …

Cell Infiltration Into A 3d Electrospun Fiber And Hydrogel Hybrid Scaffold Implanted In The Brain, Christopher J. Rivet, Kun Zhou, Ryan J. Gilbert, David I. Finkelstein, John S. Forsythe

Chemical and Biochemical Engineering Faculty Research & Creative Works

Tissue engineering scaffolds are often designed without appropriate consideration for the translational potential of the material. Solid scaffolds implanted into central nervous system (CNS) tissue to promote regeneration may require tissue resection to accommodate implantation. Or alternatively, the solid scaffold may be cut or shaped to better fit an irregular injury geometry, but some features of the augmented scaffold may fail to integrate with surrounding tissue reducing regeneration potential. To create a biomaterial able to completely fill the irregular geometry of CNS injury and yet still provide sufficient cell migratory cues, an injectable, hybrid scaffold was created to present the …

Synthesis And Characterization Of Clickable Dendrimer Hydrogels For Ocular Drug Delivery, Jingfei Tian

Theses and Dissertations

Topical medication is a standard treatment for glaucoma. However, frequent dosing makes the therapy inconvenient and patient unfriendly. There is a great need to develop new topical formulations that provide long lasting noninvasive drug release. In this thesis, novel clickable dendrimer hydrogels for anti-glaucoma drug delivery were synthesized and characterized. Polyamidoamine (PAMAM) dendrimers have been widely applied for drug delivery. The physical characteristics they possess include monodispersity, water solubility, encapsulation ability, and a large number of surface groups. Polycationic PAMAM dendrimer G3 was surface modified with alkyne-PEG5-acid and then reacted with polyethylene glycol bisazide (PEG-BA, 1100 gmol-1) through click chemistry …

Application Of Limited Mixing In The Hele–Shaw Geometry In Fabrication Of Janus Hydrogels, Md Mahmudur Rahman

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

It is widely accepted that cells behave differently responding to the stiffness of their extracellular matrix (ECM). Such observations were made by culturing cells on hydrogel substrates of tunable stiffness. However, it was recently proposed that cells may sense how strongly they are tethered to ECM, not the local stiffness of ECM. To investigate both hypotheses, we developed a method to fabricate Janus polyacrylamide (PAAM) gels. We squeeze two drops of different concentrations in the Hele-Shaw geometry to generate radial Stokes flow. When the drops coalesce, limited mixing occurs at the interface due to the narrow confinement, and diffusion normal …

An Injectable, Calcium Responsive Composite Hydrogel For The Treatment Of Acute Spinal Cord Injury, Christopher A. Mckay, Rebecca D. Pomrenke, Joshua S. Mclane, Nicholas J. Schaub, Elise K. Desimone, Lee A. Ligon, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Immediately following spinal cord injury, further injury can occur through several secondary injury cascades. As a consequence of cell lysis, an increase in extracellular Ca²⁺ results in additional neuronal loss by inducing apoptosis. Thus, hydrogels that reduce extracellular Ca²⁺ concentration may reduce secondary injury severity. The goal of this study was to develop composite hydrogels consisting of alginate, chitosan, and genipin that interact with extracellular Ca²⁺ to enable in situ gelation while maintaining an elastic modulus similar to native spinal cord (∼1000 Pa). It was hypothesized that incorporation of genipin and chitosan would regulate hydrogel electrostatic characteristics …

A Protocol For Rheological Characterization Of Hydrogels For Tissue Engineering Strategies, Jonathan M. Zuidema, Christopher J. Rivet, Ryan J. Gilbert, Faith A. Morrison

Chemical and Biochemical Engineering Faculty Research & Creative Works

Hydrogels are studied extensively for many tissue engineering applications, and their mechanical properties influence both cellular and tissue compatibility. However, it is difficult to compare the mechanical properties of hydrogels between studies due to a lack of continuity between rheological protocols. This study outlines a straightforward protocol to accurately determine hydrogel equilibrium modulus and gelation time using a series of rheological tests. These protocols are applied to several hydrogel systems used within tissue engineering applications: agarose, collagen, fibrin, Matrigel™, and methylcellulose. The protocol is outlined in four steps: (1) Time sweeps to determine the gelation time of the hydrogel. (2) …

Engineering Beta-Cell Spheroids For Type 1 Diabetes Treatment, Xiaoyan Liu

All Dissertations

Diabetes mellitus, the third most common disease in the world, is a chronic metabolic disorder caused by a failure of insulin production and/or an inability to respond to insulin. Specifically, type 1 diabetes is a disorder characterized by targeted autoimmune-directed destruction of a patient's beta-cell population within the pancreatic islets of Langerhans. The current primary treatment for type 1 diabetes is daily multiple insulin injections. However, this treatment cannot provide sustained physiological release, and the insulin amount is not finely tuned to glycemia. Pancreatic transplants or islet transplants would be the preferred treatment method but the lack of donor tissue …

Implantable Biosensors For Physiologic Status Monitoring During Hemorrhage, Christian Kotanen

All Dissertations

Trauma diagnostics and management are major aims of research for implantable amperometric enzyme biosensor technology. Biosensors are capable of monitoring metabolic variables in a minimally invasive manner and have great potential to augment current wireless vital sign monitoring technologies in order to make a more robust physiologic status monitoring platform. The dual responsive Electrochemical Cell-on-a-Chip Microdisc Electrode Array (ECC MDEA 5037) is a recently developed electrochemical transducer for use in a wireless, implantable biosensor system for the continuous measurement of interstitial glucose and lactate. Hyperglycemia arising from insulin resistance and hyperlactatemia arising from anaerobic metabolism both occur following trauma and …

Surface- And Hydrogel-Mediated Delivery Of Nucleic Acid Nanoparticles, Angela K. Pannier, Tatiana Segura

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Gene expression within a cell population can be directly altered through gene delivery approaches. Traditionally for nonviral delivery, plasmids or siRNA molecules, encoding or targeting the gene of interest, are packaged within nanoparticles. These nanoparticles are then delivered to the media surrounding cells seeded onto tissue culture plastic; this technique is termed bolus delivery. Although bolus delivery is widely utilized to screen for efficient delivery vehicles and to study gene function in vitro, this delivery strategy may not result in efficient gene transfer for all cell types or may not identify those delivery vehicles that will be efficient in vivo. …

Characterization Of Printed Skin Equivalents, Mayela R, Aldaz Cervantes, Maria Yanez, Thomas Boland

COURI Symposium Abstracts, Summer 2012

Severe burns, ulcerations, and cuts are some of the reasons people need bioengineered skin as a treatment for full-thickness wounds. When patients run out of donor sites in their own body, using the patient’s skin as a graft is no longer an option, and tissue-engineered constructs are the only possible replacement for damaged skin. The goal of this research is to develop a hydrogel-based skin graft that will be able to function as a skin replacement in full-thickness wounds while minimizing the possibility of rejection, being cost-effective, and possessing a longer shelf-life than the grafts currently in the market. Endothelial …

Nanivid : A New Research Tool For Tissue Microenvironment Studies, Waseem Khan Raja

Legacy Theses & Dissertations (2009 - 2024)

Metastatic tumors are heterogeneous in nature and composed of subpopulations of cells having various metastatic potentials. The time progression of a tumor creates a unique microenvironment to improve the invasion capabilities and survivability of cancer cells in different microenvironments. In the early stages of intravasation, cancer cells establish communication with other cell types through a paracrine loop and covers long distances by sensing growth factor gradients through extracellular matrices. Cellular migration both in vitro and in vivo is a complex process and to understand their motility in depth, sophisticated techniques are required to document and record events in real time. …

Synthesis And Characterization Of Magnetic Hydrogel Nanocomposites For Cancer Therapy Applications, Samantha Ann Meenach

University of Kentucky Doctoral Dissertations

Currently, cancer is the second leading cause of death in the United States. Conventional cancer treatment includes chemotherapy, radiation, and surgical resection, but unfortunately, all of these methods have significant drawbacks. Hyperthermia, the heating of cancerous tissues to between 41 and 45°C, has been shown to improve the efficacy of cancer therapy when used in conjunction with irradiation and/or chemotherapy. In this work, a novel method for remotely administering heat is presented. This method involves heating of tumor tissue using hydrogel nanocomposites containing magnetic nanoparticles which can be remotely heated upon exposure to an external alternating magnetic field (AMF). The …