Engineering Commons^™

Environment And Response Of 3d-Encapsulated Mesenchymal Stem Cells To Mechanical Loading, Augustus Greenwood

McKelvey School of Engineering Theses & Dissertations

This thesis explores the micromechanical environment induced when cyclically compressing hydrogels via finite element modeling and experimentally on the impact of loading on mesenchymal stem cells (MSCs) when encapsulated withing 3D hydrogel matrices. Degenerative joint diseases, characterized by cartilage degradation, present significant challenges due to cartilage's limited self-repair capacity. Innovative approaches, including stem cell-based therapies and engineered biomaterials, have emerged as promising strategies for cartilage repair and regeneration. This work specifically investigates the calibration of a bioreactor, the uniformity of load response across the hydrogel constructs via finite element modeling (FEM), and the stress response of MSCs subjected to various …

Development And Characterization Of Injectable, Cell-Encapsulated Chitosan-Genipin Hydrogels, Tyler R. Priddy-Arrington

Doctoral Dissertations

Over 150,000 patients undergo lower extremity amputation every year in the United States, most commonly caused by complications due to diabetes mellitus, peripheral vascular disease, and trauma. Diseased or damaged tissues that are unable to naturally repair themselves must either be fully removed or replaced, otherwise the injuries can lead to further complications such as infection or death. Tissue resection and amputation, as forms of removing damaged tissue, are not favorable to patients as they can cause pain, reduce mobility, and negatively impact quality of life. However, replacing lost or damaged tissues with donor tissues carries the risks of tissue …

Development And Characterization Of Shear Thinning Cnf-Tempo Hydrogels For Use In Aquaculture Vaccines, Jacob A. Holbrook

Electronic Theses and Dissertations

Aquaculture has shown significant growth within the past few decades and is expected to continue expanding rapidly as the global demand for fish consumption continues to increase. A significant loss within the aquaculture industry is due to pathogen transmission within the farm systems. These pathogens are mitigated through various methods that are not cost effective or have limited protection. The most common method of pathogen mitigation is through oil-based injection vaccines as they provide even protection across vaccinated fish and provides the longest protection compared to other vaccination methods. These oil-based injection vaccines are not without their flaws as they …

Elucidating The Mechanical And Transport Properties Of Lignin-Based Hydrogel Composites, Nicholas Gregorich

All Dissertations

The use of lignin in the fabrication of soft composites has become an emerging area of research in polymer science and polymer chemistry. These lignin-based materials present numerous benefits, notably, a reduction in the use of petroleum-based precursor, improved structural benefits to otherwise soft host polymers, as well as the inherent antimicrobial and antioxidant properties of lignin, making it suitable for biomaterials. Herein, we present two chemical reaction pathways of incorporating lignin that was fractionated and cleaned using the Aqueous Lignin Purification with Hot Agents (ALPHA) process into poly(vinyl alcohol) (PVA) hydrogel composites for aqueous-based separations. By leveraging the ALPHA …

Recent Advances In Antimicrobial Peptide Hydrogels, Aryanna Copling, Maxwell Akantibila, Raaha Kumaresan, Gilbert Fleischer, Dennise Cortes, Rahul S Tripathi, Valerie J. Carabetta, Sebastian Vega

Cooper Medical School of Rowan University Faculty Scholarship

Advances in the number and type of available biomaterials have improved medical devices such as catheters, stents, pacemakers, prosthetic joints, and orthopedic devices. The introduction of a foreign material into the body comes with a risk of microbial colonization and subsequent infection. Infections of surgically implanted devices often lead to device failure, which leads to increased patient morbidity and mortality. The overuse and improper use of antimicrobials has led to an alarming rise and spread of drug-resistant infections. To overcome the problem of drug-resistant infections, novel antimicrobial biomaterials are increasingly being researched and developed. Hydrogels are a class of 3D …

Development Of Fibroblast/Endothelial Cell-Seeded Collagen Scaffolds For In Vitro Prevascularization, Daniela S. Masson-Meyers, Fahimeh Tabatabaei, Lane Steinhaus, Jeffrey M. Toth, Lobat Tayebi

Biomedical Engineering Faculty Research and Publications

The development of vascularized scaffolds remains one of the major challenges in tissue engineering, and co-culturing with endothelial cells is known as one of the possible approaches for this purpose. In this approach, optimization of cell culture conditions, scaffolds, and fabrication techniques is needed to develop tissue equivalents that will enable in vitro formation of a capillary network. Prevascularized equivalents will be more physiologically comparable to the native tissues and potentially prevent insufficient vascularization after implantation. This study aimed to culture human umbilical vein endothelial cells (HUVECs), alone or in co-culture with fibroblasts, on collagen scaffolds prepared by simple fabrication …

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 …

Encapsulation And Culture Of Plant Protoplasts In Hydrogel Microspheres Using Droplet Microfluidics, Matthew Grasso

Graduate College Dissertations and Theses

Plant morphogenesis requires the coordinated growth between cells and their neighbors. This coordination is regulated by internal and external signals that are both physical and chemical. It is understood that both mechanical and molecular signals are involved in the regulation of plant morphogenesis however, how mechanical signals induce molecular signals and vice versa is not. This is due to a lack of research tools for manipulating and measuring the mechanical environment of growing plant cells. Such tools would ideally provide individual plant cells with mechanically tunable physical microenvironments. This may allow changes in the cells physical environment to be linked …

Growth Factor Binding Peptides In Poly (Ethylene Glycol) Diacrylate (Pegda)-Based Hydrogels For An Improved Healing Response Of Human Dermal Fibroblasts, Abigail J. Clevenger, Andrea C. Jimenez-Vergara, Erin H. Tsai, Gabriel De Barros Righes, Ana M. Díaz-Lasprilla, Gustavo E. Ramirez-Caballero, Dany J. Munoz-Pinto

Engineering Faculty Research

Growth factors (GF) are critical cytokines in wound healing. However, the direct delivery of these biochemical cues into a wound site significantly increases the cost of wound dressings and can lead to a strong immunological response due to the introduction of a foreign source of GFs. To overcome this challenge, we designed a poly(ethylene glycol) diacrylate (PEGDA) hydrogel with the potential capacity to sequester autologous GFs directly from the wound site. We demonstrated that synthetic peptide sequences covalently tethered to PEGDA hydrogels physically retained human transforming growth factor beta 1 (hTGFβ1) and human vascular endothelial growth factor (hVEGF) at 3.2 …

Advances In 3d Culture Systems For Therapeutic Discovery And Development In Brain Cancer, Janith Wanigasekara, Patrick J. Cullen, Paula Bourke, Brijesh Tiwari, James F. Curtin

Articles

This review focuses on recent advances in 3D culture systems that promise more accurate therapeutic models of the glioblastoma multiforme (GBM) tumor microenvironment (TME), such as the unique anatomical, cellular, and molecular features evident in human GBM. The key components of a GBM TME are outlined, including microbiomes, vasculature, extracellular matrix (ECM), infiltrating parenchymal and peripheral immune cells and molecules, and chemical gradients. 3D culture systems are evaluated against 2D culture systems and in vivo animal models. The main 3D culture techniques available are compared, with an emphasis on identifying key gaps in knowledge for the development of suitable platforms …

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 …

Engineering Hydrogels For Delivery Of Therapeutic Proteins, Francesca Briggs, Daryn Browne

Bioengineering Senior Theses

In this project, we investigate how innate hydrogel properties can be leveraged for controlled protein drug release platforms. Therapeutic proteins have many valuable applications within the medical field, however, professionals often face many obstacles with obtaining controlled drug release. This paper analyzes how the manipulation of hydrogel properties can improve protein drug release rates. We started these investigations by varying hydrogel concentrations since we saw that this affects the release of small molecules. Additionally, we wanted to see what the addition of a second hydrogel network would do to protein release rates. These experiments concluded that raising polymer concentrations and …

Human Induced Mesenchymal Stem Cells Display Increased Sensitivity To Matrix Stiffness., Kirstene A Gultian, Roshni Gandhi, Khushi Sarin, Martina Sladkova-Faure, Matthew Zimmer, Giuseppe Maria De Peppo, Sebastian Vega

Henry M. Rowan College of Engineering Faculty Scholarship

The clinical translation of mesenchymal stem cells (MSCs) is limited by population heterogeneity and inconsistent responses to engineered signals. Specifically, the extent in which MSCs respond to mechanical cues varies significantly across MSC lines. Although induced pluripotent stem cells (iPSCs) have recently emerged as a novel cell source for creating highly homogeneous MSC (iMSC) lines, cellular mechanosensing of iMSCs on engineered materials with defined mechanics is not well understood. Here, we tested the mechanosensing properties of three human iMSC lines derived from iPSCs generated using a fully automated platform. Stiffness-driven changes in morphology were comparable between MSCs and iMSCs cultured …

Bio-Ionic Liquid Functionalized Hydrogels Towards Smart Tissue Regeneration, Vaishali Krishnadoss

Theses and Dissertations

A blend of scaffolds, biologically active molecules, and cells are required to assemble functional constructs to repair and regenerate damaged tissue or organ via tissue engineering. The scaffold supports cell growth and proliferation and acts as a medium for diverse cellular activities. Even though hydrogel's high-water content and flexible nature make it a pronounced applicant as a scaffold, they exhibit significant technical limitations such as the absence of cell-binding motifs, lack of oxygen, conductivity, adhesive properties, growth of cells in a 3-dimensional (3D) microenvironment. In this thesis, a novel material platform is evaluated and studied to address the concerns mentioned …

Tunable Blood Shunt For Neonates With Complex Congenital Heart Defects, Ellen Garver, Christopher B. Rodell, Kristen Shema, Krianthan Govender, Samantha E. Cassel, Bryan Ferrick, Gabriella Kupsho, Ethan Kung, Kara L. Spiller, Randy Stevens, Amy L. Throckmorton

Publications

Despite advancements in procedures and patient care, mortality rates for neonatal recipients of the Norwood procedure, a palliation for single ventricle congenital malformations, remain high due to the use of a fixed-diameter blood shunt. In this study, a new geometrically tunable blood shunt was investigated to address limitations of the current treatment paradigm (e.g., Modified Blalock-Taussig Shunt) by allowing for controlled modulation of blood flow through the shunt to accommodate physiological changes due to the patient’s growth. First, mathematical and computational cardiovascular models were established to investigate the hemodynamic requirements of growing neonatal patients with shunts and to inform design …

Investigation Of Human Adipose-Derived Stem-Cell Behavior Using A Cell-Instructive Polydopamine-Coated Gelatin-Alginate Hydrogel., Settimio Pacelli, Aparna R Chakravarti, Saman Modaresi, Siddharth Subham, Kyley Burkey, Cecilia Kurlbaum, Madeline Fang, Christopher A Neal, Adam J Mellott, Aishik Chakraborty, Arghya Paul

Chemical and Biochemical Engineering Publications

Hydrogels can be fabricated and designed to exert direct control over stem cells' adhesion and differentiation. In this study, we have investigated the use of polydopamine (pDA)-treatment as a binding platform for bioactive compounds to create a versatile gelatin-alginate (Gel-Alg) hydrogel for tissue engineering applications. Precisely, pDA was used to modify the surface properties of the hydrogel and better control the adhesion and osteogenic differentiation of human adipose-derived stem cells (hASCs). pDA enabled the adsorption of different types of bioactive molecules, including a model osteoinductive drug (dexamethasone) as well as a model pro-angiogenic peptide (QK). The pDA treatment efficiently retained …

Controlled Release Of Multiple Therapeutics From Silicone Hydrogel Contact Lenses For Post-Cataract/Post-Refractive Surgery And Uveitis Treatment., Stephen A Dipasquale, Biaggio Uricoli, Matthew C Dicerbo, Thea L Brown, Mark Byrne

Henry M. Rowan College of Engineering Faculty Scholarship

PURPOSE: This work demonstrates seven-day controlled and extended in vitro physiological flow dual release of multiple post-ocular surgery therapeutics from extended-wear contact lenses as a dropless alternative for treatment of uveitis and corneal inflammation, pain, and infection. Lens replacement each week optimizes treatment matching patient recall time with the ability to increase or decrease dosage.

METHODS: Lenses were synthesized using molecular imprinting to create lenses with macromolecular memory for diclofenac sodium (DS) and dexamethasone sodium phosphate (DMSP), as well as bromfenac sodium (BS) and moxifloxacin (MOX). Drug uptake and release were analyzed, and physical properties were measured and compared to …

Bioprinting A 3d Tubular Structure With Vascular Smooth Muscle Cells To Observe The Process Compatibility, Taieba Tuba Rahman

Theses and Dissertations

Printability is the ability to print a reproducible structure using the bioprinting technique. Constructing the relationships between printability and printing parameters of the extrusion printing process is difficult because of the presence of too many independent and inter-correlated factors. For this reason, it is necessary to identify and limit the number of significantly influential factors. In addition, Scaffold based blood vessel fabrication is a key challenge in 3D Bioprinting. As vascular smooth muscle cell (VSMCs) is a major component of blood vessels, the investigation of the behavior and orientation of VSMCs after printing is required to better understand the 3D …

Effects Of Genipin Crosslinking On The Properties Of Tendon Derived Extracellular Matrix Hydrogels, Alicia Cheyenne Coombs

Theses and Dissertations

Extracellular matrix (ECM) hydrogels are a useful biomaterial in the tissue engineering field used for injectables in drug delivery systems, wound dressing, tissue regeneration and many other applications. ECM hydrogels are highly biocompatible, contain proper ratios of biomolecules required for complex bioactivity of tissues and they promote tissue repair. However, ECM hydrogels typically have poor mechanical strength, which leads to hydrogel instability, and a limitation in their ability to be modified for translational applications. In this research, genipin, a natural crosslinker derived from plants, was utilized in an attempt to improve upon the mechanical limitations of ECM hydrogels. Genipin has …

Development Of Biomaterials For Drug Delivery, Raquel De Castro

Graduate Theses and Dissertations

Drug delivery systems (DDS) have highly evolved in the last decades with the development of hydrogels and nanoparticles. However, high systemic uptake, side effects, low bioavailability, and encapsulation efficiency continue to be a major hurdle faced by such DDSs.

Nanoparticles and hydrogels can be specifically designed for targeted DDSs to mitigate some of the problems. This dissertation aimed to design two DDSs for ocular drug delivery and one for cancer treatment. The first project sought to develop chitosan nanoparticles (Cs-NP) using PEGDA as a copolymer to encapsulate gentamicin (GtS) for ocular drug delivery. Cs-NPs contain positive charges that can interact …

Discrete Element Modeling Of Hydrogel Extrusion, Rohit Boddu

Theses and Dissertations

Hydrogels are widely used in extrusion bioprinting as bioinks. Understanding how the hydrogel microstructure affects the bioprinting process aids researchers in predicting the behavior of biological components. Current experimental tools are unable to measure internal forces and microstructure variations during the bioprinting process. In this work, discrete element modeling was used to study the internal interactions and the elastic deformation of the molecular chains within hydrogel networks during the extrusion process. Two-dimensional models of hydrogel extrusions were created in Particle Flow Code (PFC; Itasca Co., Minneapolis, MN). For our model's calibration, hydrogel compression testing was used in which a cluster …

Development Of The Cell-Free Protein Biomanufacturing Platform For The Therapeutic Human Protein Production And The Topical Delivery Applications Using The Nanosized Hydrogel System, Jeehye Kim

LSU Doctoral Dissertations

Proteins are highly structural polymers, performing an enormous range of roles within organisms. Unlike synthetic polymers, proteins have a significant hierarchical ordering that can be disrupted by many environmental factors, which limits the scale-up manufacturing capability as well as the utilization of proteins as therapeutic agents. In this study, the Cell-Free Protein Synthesis (CFPS) system was developed to enhance the production capacity and applications of the therapeutic proteins. The CFPS is an advanced biosynthetic and genetic-engineered system. It enables the efficient production of proteins when the conventional cell-based protein synthesis systems cannot be applied, and when sophisticated control is required …

Complementary Techniques To Study The Behavior Of Water And The Effect On Diffusion And Degradation In Hydrogels, Paige Rockwell

Master’s Theses

Hydrogels exhibit biocompatibility in a range of biomedical applications, including drug delivery. This thesis aims to develop complementary techniques to measure the diffusion and degradation behaviors within an injectable, hydrolytically degradable hydrogel, formed via the covalent crosslinking of ethoxylated trimethylolpropane tri-3- mercaptopropionate (ETTMP) and poly(ethylene glycol) diacrylate (PEGDA), to determine its suitability as a drug delivery matrix. The characterization of water as either free, within the network openings of the hydrogel, or bound, tightly associated with the polymer chains, was determined using differential scanning calorimetry (DSC). The mobility of each type of water within the hydrogels was determined via nuclear …

Use Of Microscale Hydrophobic Surface Features For Integration Of 3d Cell Culture Into Multi-Functional Microfluidic Devices, Soroosh Torabi

Theses and Dissertations--Mechanical Engineering

3D cell culture and microfluidics both represent powerful tools for replicating critical components of the cell microenvironment; however, challenges involved in integration of the two and compatibility with standard tissue culture protocols still represent a steep barrier to widespread adoption. Here we demonstrate the use of engineered surface roughness in the form of microfluidic channels to integrate 3D cell-laden hydrogels and microfluidic fluid delivery. When a liquid hydrogel precursor solution is pipetted onto a surface containing open microfluidic channels, the solid/liquid/air interface becomes pinned at sharp edges such that the hydrogel forms the “fourth wall” of the channels upon solidification. …

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 …

Addressing Present Pitfalls In 3d Printing For Tissue Engineering To Enhance Future Potential, Jesse K. Placone, Bhushan Mahadik, John P. Fisher

Physics & Engineering Faculty Publications

Additive manufacturing in tissue engineering has significantly advanced in acceptance and use to address complex problems. However, there are still limitations to the technologies used and potential challenges that need to be addressed by the community. In this manuscript, we describe how the field can be advanced not only through the development of new materials and techniques but also through the standardization of characterization, which in turn may impact the translation potential of the field as it matures. Furthermore, we discuss how education and outreach could be modified to ensure end-users have a better grasp on the benefits and limitations …

Characterizing And Predicting The Antimicrobial Properties Of Lignin Derivatives, Ryan Kalinoski

Theses and Dissertations--Biosystems and Agricultural Engineering

Due to the overuse of antibiotics in our society, there has been a steady rise in highly antimicrobial-resistant bacteria in the last decade. This has created a renewed interest in natural phenolic compounds for antimicrobial discovery amongst the scientific community. To this end, lignin is the most abundant naturally occurring phenolic polymer on earth and has already been known to have antimicrobial properties due to its polyphenolic structure. In addition, lignin is considered a major waste product for lignocellulosic biorefineries, and its valorization into value-added products will generate extra profit for a biorefinery, making biofuels less expensive, increasing their marketability …

Effects Of Crosslinking Conditions On Biofouling Of Polymer Substrates With A Hydrogel Layer, Laura Davila

Williams Honors College, Honors Research Projects

The introduction of a hydrogel coating to a surface has been looked at for different benefits. Certain hydrogels offer antifouling properties that are beneficial to different applications like medical components. Previous attempts (2) (3)have been done to introduce a hydrogel surface to plastic substrates. One of them is to use grafting brushes which works properly but it is not sufficient since the layer is too thin and therefore can be damaged. The second method have a bulkier coating without crosslinking. Opposite to grafting brushes this method has too thick of a layer. Additionally, there is no crosslink therefore the coating …

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 …

Mechanosensitive Epithelial Cell Scattering And Migration On Layered Matrices, Christopher Michael Walter

McKelvey School of Engineering Theses & Dissertations

Epithelial cells form multi-layered tissue scaffolding that makes up every organ in the body. Along with epithelial cells, the basement membrane (BM) and connective tissue are composed of various proteins that sculpt the organs and protect them from foreign macromolecules. Epithelial cells respond to various cues, both chemical and mechanical, from their surrounding matrices to aid in maintenance and repair of these layers through degradation and deposition of extracellular matrix (ECM) proteins. In cancer progression, epithelial cells lose their normal function of supporting tissue structure and instead adopt more aggressive behaviors through an epithelial-to-mesenchymal transition (EMT) of their cellular traits. …