Biomedical Engineering and Bioengineering Commons^™

Application Of Halloysite Nanotubes In Bone Disease Remediation And Bone Regeneration, Yangyang Luo

Doctoral Dissertations

Customized patient therapy has been a major research focus in recent years. There are two research fields that have made a significant contribution to realizing individualized-based treatment: targeted drug delivery and three-dimensional (3D) printing technology. With benefit from the advances in nanotechnology and biomaterial science, various drug delivery systems have been established to provide precise control of therapeutic agents release in time and space. The emergence of three-dimensional (3D) printing technology enables the fabrication of complicated structures that effectively mimic native tissues and makes it possible to print patient-specific implants. My dissertation research used a clay nanoparticle, halloysite, to develop …

Investigation Of The Effect Of Age On Regenerative Outcomes Following Treatment Of Volumetric Muscle Loss Injuries, John Taehwan Kim

Graduate Theses and Dissertations

Volumetric muscle loss (VML) is a traumatic injury in skeletal muscle resulting in the bulk loss of more than 20% of the muscle’s volume. Included in the bulk loss of muscle is the skeletal muscle niche comprised of nerve bundles, vasculature, local progenitor cells, basal lamina, and muscle fibers, overwhelming innate repair mechanisms. The hallmark of VML injury is the excessive accumulation of non-contractile, fibrotic tissue and permanent functional deficits. Though predominant in the younger demographic, the elderly population is also captured within VML injuries. There are many factors that change with aging in skeletal muscle that may further hinder …

Bioengineering Extracellular Matrix Scaffolds For Volumetric Muscle Loss, Kevin Roberts

Graduate Theses and Dissertations

Volumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in fibrosis and severe functional deficits which have defied clinical repair strategies. My work spans the design and preclinical evaluation of implants intended to drive the cell community of injured muscle toward a regenerative state, as well as the development of an understanding of the molecular responses of this cell community to biomaterial interventions. I demonstrate a new class of biomaterial by leveraging the productive capacity of sacrificial hollow fiber membrane cell culture; I show specifically that unique threads of whole extracellular matrix can be isolated by solvent degradation …

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 …

Disciplinary Learning From An Authentic Engineering Context, Catherine Langman, Judith Zawojewski, Patricia Mcnicholas, Ali Cinar, Eric Brey, Mustafa Bilgic, Hamidreza Mehdizadeh

Journal of Pre-College Engineering Education Research (J-PEER)

This small-scale design study describes disciplinary learning in mathematical modeling and science from an authentic engineeringthemed module. Current research in tissue engineering served as source material for the module, including science content for readings and a mathematical modeling activity in which students work in small teams to design a model in response to a problem from a client. The design of the module was guided by well-established principles of model-eliciting activities (a special class of problem-solving activities deeply studied in mathematics education) and recently published implementation design principles, which emphasize the portability of model-eliciting activities to many classroom settings.

Two …

Design And Mechanical Characterization Of 3d Printed Gradient Porosity Poly(Propylene Fumarate) Scaffolds, Andrea Felicelli

Williams Honors College, Honors Research Projects

Worldwide incidence of bone disorders and conditions, an already prevalent problem, is expected to double by 2020 from the rate in 2013 due to factors such as higher life expectancies and lower levels of physical activity. Every year in the United States, over half a million patients receive bone defect repairs, with costs greater than $2.5 billion. Current repairs are typically done with bone grafts, which are often costly and can result in added complications in the donor surgical site. Tissue engineering, a growing field that seeks to assist and enhance tissue defect repairs through the use of synthetic materials, …

Consistent And Reproducible Cultures Of Large-Scale 3d Mammary Epithelial Structures Using An Accessible Bioprinting Platform, John A. Reid, Peter M. Mollica, Robert D. Bruno, Patrick C. Sachs

Medical Diagnostics & Translational Sciences Faculty Publications

Background: Standard three-dimensional (3D) in vitro culture techniques, such as those used for mammary epithelial cells, rely on random distribution of cells within hydrogels. Although these systems offer advantages over traditional 2D models, limitations persist owing to the lack of control over cellular placement within the hydrogel. This results in experimental inconsistencies and random organoid morphology. Robust, high-throughput experimentation requires greater standardization of 3D epithelial culture techniques.

Methods: Here, we detail the use of a 3D bioprinting platform as an investigative tool to control the 3D formation of organoids through the "self-assembly" of human mammary epithelial cells. Experimental bioprinting procedures …

Developmental Steps For A Functional Three-Dimensional Cell Culture System For The Study Of Asymmetrical Division Of Neural Stem Cells, Martina Zamponi

Biomedical Engineering Theses & Dissertations

Stem cells are a cell type present during and following development, which possess self- renewal properties, as well as the ability to differentiate into specific cells. Asymmetrical division is the cellular process that allows stem cells to produce one differentiated and one un-differentiated daughter cell during the same mitotic event. Insights in the molecular mechanisms of such process are minimal, due to the absence of effective methods for its targeted study. Currently, traditional methods of investigation include monolayer cell culture and animal models. The first poses structural limitations to the accurate representation of human tissue and cell structures, while animal …

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 …

Application Of Composite Hydrogels To Control Physical Properties In Tissue Engineering And Regenerative Medicine, Cassidy Sheffield, Kaylee Meyers, Emil Johnson, Rupak Rajachar

Michigan Tech Publications

The development of biomaterials for the restoration of the normal tissue structure–function relationship in pathological conditions as well as acute and chronic injury is an area of intense investigation. More recently, the use of tailored or composite hydrogels for tissue engineering and regenerative medicine has sought to bridge the gap between natural tissues and applied biomaterials more clearly. By applying traditional concepts in engineering composites, these hydrogels represent hierarchical structured materials that translate more closely the key guiding principles required for improved recovery of tissue architecture and functional behavior, including physical, mass transport, and biological properties. For tissue-engineering scaffolds in …

Recent Developments In Tough Hydrogels For Biomedical Applications, Yuan Liu, Weilue He, Zhongtian Zhang, Bruce P. Lee

Department of Biomedical Engineering Publications

A hydrogel is a three-dimensional polymer network with high water content and has been attractive for many biomedical applications due to its excellent biocompatibility. However, classic hydrogels are mechanically weak and unsuitable for most physiological load-bearing situations. Thus, the development of tough hydrogels used in the biomedical field becomes critical. This work reviews various strategies to fabricate tough hydrogels with the introduction of non-covalent bonds and the construction of stretchable polymer networks and interpenetrated networks, such as the so-called double-network hydrogel. Additionally, the design of tough hydrogels for tissue adhesive, tissue engineering, and soft actuators is reviewed.

3d Printed Pla Scaffolds To Promote Healing Of Large Bone Defects, Jacob W. Cole, Tiera Martinelli, Mitchell T. Ryan, Sarah G. Seman, Daniel Sidle, Stephen R. Smith, Rocco J. Rotello, Timothy L. Norman

The Research and Scholarship Symposium (2013-2019)

One challenge modern medicine faces is the ability to repair large bone defects and stimulate healing. Small defects typically heal naturally, but large bone defects do not and current solutions are to replace the missing tissue with biologically inert materials such as titanium. This limits the amount of bone healing as the defect is not repaired but rather replaced. The focus of our research is to develop a method of using 3D printing to create biodegradable scaffolds which promote bone in-growth and replacement. To accomplish this we used poly lactic acid (PLA) filament and a desktop 3D printer. To promote …

3d Bioprinting Systems For The Study Of Mammary Development And Tumorigenesis, John Reid

Electrical & Computer Engineering Theses & Dissertations

Understanding the microenvironmental factors that control cell function, differentiation, and stem cell renewal represent the forefront of developmental and cancer biology. To accurately recreate and model these dynamic interactions in vitro requires both precision-controlled deposition of multiple cell types and well-defined three-dimensional (3D) extracellular matrix (ECM). To achieve this goal, we hypothesized that accessible bioprinting technology would eliminate the experimental inconsistency and random cell-organoid formation associated with manual cell-matrix embedding techniques commonly used for 3D, in vitro cell cultures. The first objective of this study was to adapt a commercially-available, 3D printer into a 3D bioprinter. Goal-based computer simulations were …

Osteon Mimetic Scaffolding, Janay Clytus

Senior Theses

The purpose of this research is to provide an alternative to naturally derived bone grafts. There is a gap in the supply of donors and the demand of bone tissue. Artificial scaffold creation can work as an implant and decrease the shortage of bone grafts and increase the range of injuries that can be repaired. Current research focuses on optimizing mechanical properties such as porosity, improving vascularization using cells, and generating osteoconductivity. For osteodifferentiation, mesenchymal stem cells (MSCs) can differentiate into mesodermal lineages such as chondrocytes, osteoblasts, adipocytes, and tenocytes by supplementing cultures with lineage-specific soluble factors (Marchetti). Co-culturing ECFCs …

3d Tissue Engineering, An Emerging Technique For Pharmaceutical Research, Gregory Jensen, Christian Morrill, Yu Huang

Biological Engineering Faculty Publications

Tissue engineering and the tissue engineering model have shown promise in improving methods of drug delivery, drug action, and drug discovery in pharmaceutical research for the attenuation of the central nervous system inflammatory response. Such inflammation contributes to the lack of regenerative ability of neural cells, as well as the temporary and permanent loss of function associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and traumatic brain injury. This review is focused specifically on the recent advances in the tissue engineering model made by altering scaffold biophysical and biochemical properties for use in the treatment of neurodegenerative diseases. …

Engineering Hyaluronic Acid Carbon Nanotube Nanofibers: A Peripheral Nerve Interface To Electrically Stimulate Regeneration, Elisabeth M. Steel

Wayne State University Dissertations

Peripheral nerve injuries annually affect hundreds of thousands of people globally. Current treatments like the gold standard autograft and commercially available nerve guide conduits (NGC) are insufficient to repair long gap peripheral nerve injuries. NGCs can aid recovery but lack key microenvironment cues that promote nerve regeneration. We hypothesized that providing topographical, mechanical, and electrical guidance cues through a nanofibrous composite biopolymer would result in improved neuron growth metrics using an in vitro model. We embedded hydrophilic carbon nanotubes (CNT) within hyaluronic acid (HA) nanofibers by electrospinning. The aims of this study were (1) to define the topographical, nanomechanical, and …

Molded Features In Pdms For Fabricating Bacterial Cellulose For Various Geometries, Mitchell Habegger

Williams Honors College, Honors Research Projects

The purpose of producing features on bacterial cellulose (BC) is to facilitate the elongation and alignment for cells, in this case Normal Human Dermal Fibroblast (NHDF) cells. The elongated cells have applications in wound healing, tissue engineering, disease diagnostics, and many other fields. Experiments were run to test the effectiveness of transferring features to BC sheets from features induced by fracturing on polydimethylsiloxane (PDMS) and those duplicated from molds with existing features. The features were duplicated to BC sheets by either air drying or Guided Assembly-Based Biolithography (GAB). The research results showed that fracture inducing on PDMS produced very small …

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 …

Effects Of Uniaxial Cyclic Strain On Endothelial Progenitor Cells, Maria Alejandra Zeballos Castro

Biomedical Engineering Undergraduate Honors Theses

Despite the high prevalence of calcific aortic valve disease (CAVD), the underlying mechanisms of pathogenesis have not been found yet. Therefore, it is extremely important to study CAVD and understand how it develops. For this matter, we decided to study the potential of endothelial progenitor cells (EPCs) for use in tissue-engineered models of heart valves. EPCs were chosen as the cell source of interest for this study due to their high neovascularization potential and use in regenerative medicine and cardiovascular tissue engineering.

In this project, we aimed to engineer the microenvironment of cells that are involved in the formation of …

Three-Dimensional Microfluidic Tumor Vascular Model For Investigating Breast Cancer Metastasis, Anastasiia Vasiukhina, Brian H. Jun, Luis Solorio, Pavlos P. Vlachos

The Summer Undergraduate Research Fellowship (SURF) Symposium

Metastasis is one of the primary reasons for the high mortality rates in female patients diagnosed with breast cancer. It involves the migration of cancer cells into the circulatory system allowing for the dissemination of cancer cells in distal tissues. Understanding the major processes that occur in cells and tissues during metastasis can help improve currently existing therapeutic methods. In order to understand such mechanisms, developing physiologically relevant tissue models is crucial. Advancements in microfluidics have led to the fabrication of 3D culture models with shear stress gradients and flow control that can recapitulate aspects of the tumor microenvironment in …

Development And Characterization Of Tissue Engineered Blood Vessel Mimics Under "Diabetic" Conditions, Shelby Gabrielle Kunz

Master's Theses

The development of tissue engineered blood vessel mimics for the testing of intravascular devices in vitro has been established in the Cal Poly tissue engineering lab. Due to the prevalence of cardiovascular disease in diabetic patients and minimal accessible studies regarding the interactions between diabetes and intravascular devices used to treat vascular disease, there is a need for the development of diabetic models that more accurately represents diabetic processes occurring in the blood vessels, primarily endothelial dysfunction. This thesis aimed to create a diabetic blood vessel mimic by implementing a high glucose environment for culturing human endothelial cells from healthy …

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. …

3d Printing Of Biodegradable Scaffolds For Tissue Engineering Applications, Joe Morin, Michael Pickett, Amy Abraham, Tiera Martinelli

The Research and Scholarship Symposium (2013-2019)

With the recent improvements in three dimensional (3D) printing technologies, the potential for tissue engineering and regenerative medicine have significantly improved. One key idea in tissue engineering is to specifically design scaffolds to aid in the healing process by being incorporated into the body’s own tissue. The overall goal of this project is to investigate 3D printable scaffold design to access suitability for tissue replacement. This was accomplished by analyzing the effect of the material used to create the scaffolds, pore size, and pore shape on mechanical stiffness and cell culturability. Based on published literature, it was determined that, depending …

Development Of A Programmed Electrospun Three Dimensional (3d) Nanofiber Collecter And It’S Application To Orthopedic Implant Coatings, Liang Chen

Wayne State University Dissertations

Orthopedic implants might not directly unite with bones especially in compromised patients even if they have been appropriately fixed. The lack of early osseointegration would lead to the failure of the orthopedic implant. A “bone-like” implant surface is urgently needed to accelerate osseointegration. Electrospun nanofiber (NF) is a promising implant coating due to its highly porous nanoscale structure. It mimics the collagen I nanofibrous network of bone tissue; meanwhile it has been widely used as a drug delivery device. However, its compact and dense structure is not ideal for cell growth. Our strategy was to develop a functional three-dimensional (3D) …

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 …

Developing Afm Techniques For Testing Peg Hydrogels, Hannah L. Cebull, Jessica Stukel, Rebecca Willits

Williams Honors College, Honors Research Projects

Many instruments are used to find elastic properties of biological samples using methods such as tensile and bending tests, but using the atomic force microscope (AFM) is considered a non-destructive method because it can provide repeated local stiffness information without damaging the sample. It additionally allows the sample to be tested in an aqueous environment, which is optimal for soft materials such as hydrogels. The nanoindentation is performed via cantilever, measuring the deflection of the cantilever during the contact of the sample using a laser. Compared to hard samples, testing soft materials can present more challenges when working with the …

Biophysical Characterization And Theoretical Analysis Of Molecular Mechanisms Underlying Cell Interactions With Poly(N-Isopropylacrylamide) Hydrogels, Michael C. Cross

USF Tampa Graduate Theses and Dissertations

So-called, “Dynamic biomaterials” comprised of stimuli-responsive hydrogels are useful in a wide variety of biomedical applications including tissue engineering, drug delivery, and biomedical implants. More than 150,000 peer-reviewed articles (as of 2016) have been published on these materials, and more specifically, over 100,000 of these are on the most widely studied, poly(N-isopropylacrylamide). This thermoresponsive polymer in a crosslinked hydrogel network undergoes a large volume phase transition (𝑉/𝑉₀ ~ 10 − 100) within a small temperature range (𝑇 ~ 1 − 3𝐾) making it particularly useful for tissue engineering applications because of the ability to control the topographical configuration of …

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 …

Densified Collagen-Fibril Biomaterials For Bone Tissue Engineering, Lauren E. Watkins

Open Access Theses

Millions of craniofacial bone defects occur annually as a result of trauma, congenital defects, disease, or tooth extraction. When present in the oral cavity, these defects are associated with adverse impacts on speech, mastication, and aesthetics. Thus, there is a clinical need for interventional strategies to restore and preserve alveolar bone mass to improve the success of future treatment options intended to reestablish functionality and aesthetics. Guided bone regeneration using bone grafts and a membrane represent the current standard of care for repairing alveolar bone defects, but face a number of limitations related to resorption time and structural integrity. Improvements …

Accessible Bioprinting: Adaptation Of A Low-Cost 3d-Printer For Precise Cell Placement And Stem Cell Differentiation, John A. Reid, Peter A. Mollica, Garett D. Johnson, Roy C. Ogle, Robert D. Bruno, Patrick C. Sachs

Medical Diagnostics & Translational Sciences Faculty Publications

The precision and repeatability offered by computer-aided design and computer-numerically controlled techniques in biofabrication processes is quickly becoming an industry standard. However, many hurdles still exist before these techniques can be used in research laboratories for cellular and molecular biology applications. Extrusion-based bioprinting systems have been characterized by high development costs, injector clogging, difficulty achieving small cell number deposits, decreased cell viability, and altered cell function post-printing. To circumvent the high-price barrier to entry of conventional bioprinters, we designed and 3D printed components for the adaptation of an inexpensive 'off-the-shelf' commercially available 3D printer. We also demonstrate via goal based …