Biomedical Engineering and Bioengineering Commons^™

Nanomechanics Of Electrospun Nanofibres For Tissue Engineering Of The Tympanic Membrane, Sara Makaremi

Electronic Thesis and Dissertation Repository

The Tympanic Membrane (TM), also known as the eardrum, includes layers of organized collagen nanofibres which play an essential role in sound transmission. Perforations that are caused by infection or accident must be repaired in order to restore hearing. Tympanoplasty is performed using grafts that are prepared from bladder, cartilage, temporal fascia and cadaveric skin. However, since mechanical properties of these grafts do not match those of the original TM, normal hearing is not fully restored. The goal of this study is to develop nanofibrous scaffolds for tissue engineering of the TM in order to circumvent the complications addressed with …

Melt Blown Poly(Lactic Acid) For Application As A Tissue Engineering Scaffold, William Horst Gazzola

Masters Theses

Poly(lactic acid) (PLA) was melt blown (MB) under varying processing conditions to create webs with micro and nano-architecture. Processing parameters varied were primary air flow rate and collector distance. In total, twenty-one webs were produced and the physical properties of the webs were investigated including, mean fiber diameter and fiber diameter distribution, mean pore diameter and pore size distribution, web thickness, degree of crystallinity, tensile modulus and degradation rate. Four webs, two with micro and two with nano-architecture, thought suitable for use as tissue engineering scaffolds were selected for seeding with A375 human malignant melanoma cells. Cell culture was conducted …

Nanoroughened Surfaces For Efficient Capture Of Circulating Tumor Cells Without Using Capture Antibodies, Weiqiang Chen, Shinuo Weng, Feng Zhang, Steven Allen, Xiang Li, Liwei Bao, Raymond H. W. Lam, Jill A. Macoska, Sofia D. Merajver, Jianping Fu

Weiqiang Chen

Circulating tumor cells (CTCs) detached from both primary and metastatic lesions represent a potential alternative to invasive biopsies as a source of tumor tissue for the detection, characterization and monitoring of cancers. Here we report a simple yet effective strategy for capturing CTCs without using capture antibodies. Our method uniquely utilized the differential adhesion preference of cancer cells to nanorough surfaces when compared to normal blood cells and thus did not depend on their physical size or surface protein expression, a significant advantage as compared to other existing CTC capture techniques.

Calcium Phosphate-Based Resorbable Biomaterials For Bone Regeneration, Daniel O. Costa

Electronic Thesis and Dissertation Repository

Bone defects are a prevalent problem in orthopedics and dentistry. Calcium phosphate-based coatings and nanocomposites offer unique solutions towards producing scaffolds with suitable physical, mechanical and biological properties for bone regeneration.

We developed a novel method to synthesize hydroxyapatite (HA) particles with high aspect ratio using sol-gel chemistry and hydrothermal treatment. We obtained tunable pure-phase carbonated-HA in the form of micro/nanorods and nanowires (diameters 25-800 nm). To mimic the structure of bone, HA nanowires were homogenously mixed within poly(ε-caprolactone) (PCL) to produce nanocomposites with improved mechanical properties as determined by uniaxial tensile testing.

Surface chemistry and topography of biomaterials play …

Quaternary Ammonium Silane-Functionalized, Methacrylate Resin Composition With Antimicrobial Activities And Self-Repair Potential, Shi-Qiang Gong, Li-Na Niu, Lisa K. Kemp, Cynthia K.Y. Yiu, Heonjune Ryou, Yi-Pin Qi, John D. Blizzard, Sergey Nikonov, Martha G. Brackett, Regina L.W. Messer, Christine D. Wu, Jing Mao, L. Bryan Brister, Frederick A. Rueggeberg, Dwayne D. Arola, David H. Pashley, Franklin R. Tay

Faculty Publications

The design of antimicrobial polymers to address healthcare issues and minimize environmental problems is an important endeavor with both fundamental and practical implications. Quaternary ammonium silane-functionalized methacrylate (QAMS) represents an example of antimicrobial macromonomers synthesized by a sol–gel chemical route; these compounds possess flexible Si–O–Si bonds. In present work, a partially hydrolyzed QAMS co-polymerized with 2,2-[4(2-hydroxy 3-methacryloxypropoxy)-phenyl]propane is introduced. This methacrylate resin was shown to possess desirable mechanical properties with both a high degree of conversion and minimal polymerization shrinkage. The kill-on-contact microbiocidal activities of this resin were demonstrated using single-species biofilms of Streptococcus mutans (ATCC 36558), Actinomyces naeslundii (ATCC …

Poly(Vinyl Alcohol) Nanocomposite Hydrogels For Intervertebral Disc Prostheses, Elaine Wong

Electronic Thesis and Dissertation Repository

Spinal fusion is currently the gold standard for surgical intervention of intervertebral disc (IVD) diseases leading to neck and back pain failing conservative treatments. However, fusion removes motion between the vertebrae and can result in adjacent level degeneration. Total disc replacement (TDR) is an emerging treatment alternative that preserves motion, but materials found in clinically available devices bear little resemblance to the properties of the native IVD. Poly(vinyl alcohol) (PVA) hydrogels are biocompatible, have mechanical behaviour similar to natural tissues, and properties that can be tuned by varying polymer concentration and physical crosslinking through freeze-thaw cycling. Furthermore, their properties can …

Modulation Of Bone And Nerve Cell Behavior Using Biodegradable Polymer Networks, Lei Cai

Doctoral Dissertations

This dissertation presents novel biodegradable and photo-crosslinkable building blocks to achieve polymer networks with controlled surface chemistry, stiffness, and topographical features for investigating cell-material interactions and targeting hard and soft tissue engineering applications. Chapter I reviews the recent progress in polymeric gel systems and how their physical properties can be tailored to regulate cell functions and satisfy the clinical needs. Chapter II presents a facile method to synthesize photo-crosslinkable poly(epsilon-caprolactone) acrylates (PCLAs) and reveal tunable cell responses to photo-crosslinked PCLAs. Chapter III investigates the mechanism of colorization in preparing crosslinkable polymers by reacting hydroxyl-containing polymers with unsaturated anhydrides or acyl …

Effect Of Applied Uniaxial Stress On Rate And Mechanical Effects Of Cross-Linking In Tissue-Derived Biomaterials, Debbie Chachra, Paul Gratzer, Christopher Pereira, J. Lee

Debbie Chachra

Conformational changes in collagen fibrils, and indeed the triple helix, can be produced by application of mechanical stress or strain. We have demonstrated that the rate of cross-linking in glutaraldehyde and epoxide homobifunctional reagents can be modulated by uniaxial stress (strain). Two poly(glycidyl ether) epoxides were used: Denacol^® EX-810 (a small bifunctional reagent), and Denacol EX-512 (a large polyfunctional reagent). To prevent any possible effect from being masked by saturation of cross-linking sites, bovine pericardium was cross-linked to such an extent that the increase in collagen denaturation temperature, T_d, was one-half of the maximal rise achievable with …

Propagation Of Ultrasound Through Freshly Excised Human Calvarium, Armando Garcia Noguera

Department of Engineering Mechanics: Dissertations, Theses, and Student Research

The propagation of ultrasound through complex biological media, such as the human calvarium, poses a great challenge for modern medicine. Several ultrasonic techniques commonly used for treatment and diagnosis in most of the human body are still difficult to apply to the human brain, in part, because of the properties of the skull. Moreover, an understanding of the biomechanics of transcranial ultrasound may provide needed insight into the problem of blast wave induced traumatic brain injury (TBI). In the present study, the spatial variability of ultrasonic properties was evaluated for relevant frequencies of 0.5, 1, and 2.25 MHz. A total …

Development Of In Vitro Tissue Engineered Blood Vessel Mimics In Complex Geometries For Coronary Stent Testing, Robert Dalton Chavez

Master's Theses

Coronary heart disease is the leading cause of death in the United States and occurs when plaque occludes coronary arteries. Coronary stents, which may be used to treat coronary occlusions, are small metal tubes that are implanted in coronary arteries to restore blood flow. After stent implantation, endothelial cells grow over the stent so that blood contacts the endothelial cells instead of the stent surface; this event is known as re-endothelialization. Re-endothelialization prevents blood from clotting on the stent surface and is a good predictor of stent success. Blood vessel mimics (BVMs) are in vitro tissue engineered models of human …

Corrosion Of Stainless Steel 316l And Astm F75 Cobalt Chromium Alloy During Immersion Testing In Silver Salt Solutions, Meagan Higgins

Materials Engineering

This study evaluates the potential effects of silver salts on biocompatible metals used for prostheses during the chemical reduction process to produce a silver antimicrobial layer on the metal’s surface. Samples of two biocompatible metals were obtained: Stainless Steel 316L and ASTM F75 Cobalt Chromium Alloy. Three different silver salts were also acquired: silver nitrate, silver sulfadiazine, and silver chloride. Specimens of each metal were cut to size using a 4-1/2 inch aluminum oxide, 40 grit, cut off wheel for metal, attached to a Dewalt Angle Grinder. The biocompatible metal samples were then subject to either Solution 1, water with …

Design Of Experimentation To Systematically Determine The Interaction Between Electrospinning Variables And To Optimize The Fiber Diameter Of Electrospun Poly (D, L-Lactide-Co-Glycolide) Scaffolds For Tissue Engineered Constructs, Yvette S. Castillo

Master's Theses

Cardiac disease causes approximately a third of the deaths in the United States. Furthermore, most of these deaths are due to a condition termed atherosclerosis, which is a buildup of plaque in the coronary arteries, leading to occlusion of normal blood flow to the cardiac muscle. Among the methods to treat the condition, stents are devices that are used to restore normal blood flow in the atherosclerotic arteries. Before advancement can be made to these devices and changes can be tested in live models, a reliable testing method that mimics the environment of the native blood vessel is needed. Dr. …

The Characterization Of Biofilm Attachment To Metal Interfaces: Effects Of Substratum Properties, Marcel D. Mendes

Master's Theses

Bacteria are among the most abundant microorganisms on earth, and can be found in essentially every environment. When a clean surface is exposed to media containing planktonic bacteria, the bacterial cells will attach to the surface and aggregate to form what is known as a biofilm. Biofilms have been shown to negatively affect many industries including medical, industrial, and food science applications. While biofilms have been well characterized from a microbiology perspective, there has been much less research from a materials science standpoint. It is hypothesized that the material properties of the substratum (such as the micro-structure) have a significant …

Growth And Expression Of Halorhodopsin For Application In A Protein-Based Artificial Retina, Megan Ryan Gillespie

Honors Scholar Theses

Halorhodopsin (HR), a light-activated chloride ion pump, demonstrates potential for use as the scaffolding in an artificial retina. Retinal implants are needed to restore vision to people afflicted with ophthalmic diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). A protein-based chloride ion-patch would be utilized by the eye to create an influx of chloride ions, similar to ion concentrations in healthy retinas during the conversion of light stimuli to electrochemical signals. This protein-based retinal prosthesis will directly stimulate the bipolar cells of the retina, replacing the function of damaged photoreceptor cells. Other alternative treatments for AMD and …

Stability Of A Microvessel Subject To Structural Adaptation Of Diameter And Wall Thickness, Alisha Sarang-Sieminski, John Geddes, Ilari Shafer, Rachel Nancollas, Morgan Boes

John B. Geddes

Vascular adaptation—or structural changes of microvessels in response to physical and metabolic stresses—can influence physiological processes like angiogenesis and hypertension. To better understand the influence of these stresses on adaptation, Pries et al. (1998, 2001a,b, 2005) have developed a computational model for microvascular adaptation. Here, we reformulate this model in a way that is conducive to a dynamical systems analysis. Using th ese analytic methods, we determine the equilibrium geometries of a single vessel under different conditions and classify its type of stability. We demonstrate that our closed-form solution for vessel geometry exhibits the same regions of stability as the …

Engineering Strategies To Recapitulate Epithelial Morphogenesis Within Synthetic Three-Dimensional Extracellular Matrix With Tunable Mechanical Properties, Alisha Sarang-Sieminski, Yekaterina Miroshnikova, D Jorgens, L Spirio, M Auer, V Weaver

Alisha L. Sarang-Sieminski

The mechanical properties (e.g. stiffness) of the extracellular matrix (ECM) influence cell fate and tissue morphogenesis and contribute to disease progression. Nevertheless, our understanding of the mechanisms by which ECM rigidity modulates cell behavior and fate remains rudimentary. To address this issue, a number of two and three-dimensional (3D) hydrogel systems have been used to explore the effects of the mechanical properties of the ECM on cell behavior. Unfortunately, many of these systems have limited application because fiber architecture, adhesiveness and/or pore size often change in parallel when gel elasticity is varied. Here we describe the use of ECM-adsorbed, synthetic, …

Self-Assembling Short Oligopeptides And The Promotion Of Angiogenesis, Alisha Sarang-Sieminski, Daria Narmoneva, Olumuyiwa Oni, Shugang Zhang, Jonathan Gertler, Roger Kamm, Richard Lee

Alisha L. Sarang-Sieminski

Because an adequate blood supply to and within tissues is an essential factor for successful tissue regeneration, promoting a functional microvasculature is a crucial factor for biomaterials. In this study, we demonstrate that short self-assembling peptides form scaffolds that provide an angiogenic environment promoting long-term cell survival and capillary-like network formation in three-dimensional cultures of human microvascular endothelial cells. Our data show that, in contrast to collagen type I, the peptide scaffold inhibits endothelial cell apoptosis in the absence of added angiogenic factors, accompanied by enhanced gene expression of the angiogenic factor VEGF. In addition, our results suggest that the …

Primary Sequence Of Ionic Self-Assembling Peptide Gels Affects Endothelial Cell Adhesion And Capillary Morphogenesis, Alisha Sarang-Sieminski, C. Semino, Haiyan Gong, Roger Kamm

Alisha L. Sarang-Sieminski

Appropriate choice of biomaterial supports is critical for the study of capillary morphogenesis in vitro as well as to support vascularization of engineered tissues in vivo. Self-assembling peptides are a class of synthetic, ionic, oligopeptides that spontaneously assemble into gels with an ECM-like microarchitecture when exposed to salt. In this paper, the ability of four different self-assembling peptide gels to promote endothelial cell adhesion and capillary morphogenesis is explored. Human umbilical vein endothelial cells (HUVECs) were cultured within ionic self-assembling peptide family members, RAD16-I ((RADA)₄), RAD16-II ((RARADADA)₂), KFE-8 ((FKFE)₂), or KLD-12 ((KLDL)₃). …

Biomaterial-Microvasculature Interactions, Alisha Sarang-Sieminski, Keith Gooch

Alisha L. Sarang-Sieminski

The utility of implanted sensors, drug-delivery systems, immunoisolation devices, engineered cells, and engineered tissues can be limited by inadequate transport to and from the circulation. As the primary function of the microvasculature is to facilitate transport between the circulation and the surrounding tissue, interactionsbetween biomaterials and the microvasculature have been explored to understand the mechanisms controlling transport to implanted objects and ultimately improve it. This review surveys work on biomaterial-microvasculature interactions with a focus on the use of biomaterials to regulate the structure and function of the microvasculature. Several applications in which biomaterial-microvasculature interactions play a crucial role are briefly …

The Relative Magnitudes Of Endothelial Force Generation And Matrix Stiffness Modulate Capillary Morphogenesis In Vitro, Alisha Sarang-Sieminski, Robert Hebbel, Keith Gooch

Alisha L. Sarang-Sieminski

When suspended in collagen gels, endothelial cells elongate and form capillary-like networks containing lumens. Human blood outgrowth endothelial cells (HBOEC) suspended in relatively rigid 3 mg/ml floating collagen gels, formed in vivo-like, thin, branched multi-cellular structures with small, thick-walled lumens, while human umbilical vein endothelial cells (HUVEC) formed fewer multi-cellular structures, had a spread appearance, and had larger lumens. HBOEC exert more traction on collagen gels than HUVEC as evidenced by greater contraction of floating gels. When the stiffness of floating gels was decreased by decreasing the collagen concentration from 3 to 1.5 mg/ml, HUVEC contracted gels more and formed …

Nanotopography Influences Adhesion, Spreading, And Self-Renewal Of Human Embryonic Stem Cells, Weiqiang Chen, Luis G. Villa-Diaz, Yubing Sun, Shinuo Weng, Jin Koo Kim, Raymond H. W. Lam, Lin Han, Rong Fan, Paul H. Krebsbach, Jianping Fu

Weiqiang Chen

Human embryonic stem cells (hESCs) have great potentials for future cell-based therapeutics. However, their mechanosensitivity to biophysical signals from the cellular microenvironment is not well characterized. Here we introduced an effective microfabrication strategy for accurate control and patterning of nanoroughness on glass surfaces. Our results demonstrated that nanotopography could provide a potent regulatory signal over different hESC behaviors, including cell morphology, adhesion, proliferation, clonal expansion, and self-renewal. Our results indicated that topological sensing of hESCs might include feedback regulation involving mechanosensory integrin-mediated cell matrix adhesion, myosin II, and E-cadherin. Our results also demonstrated that cellular responses to nanotopography were cell-type …

Evaluation Of Decellularization Procedures For Porcine Arteries, Charles Clapp

Biomedical Engineering

Coronary artery disease has become the leading cause of death in the United States, with over 425,000 deaths in 2006. Stenting has evolved into the preferred preventative technique for myocardial infarction by opening up an occluded artery, due to its low invasiveness compared to the alternative of coronary artery bypass grafting. Bare metal stents have been improved by coating with anti-proliferative drugs to advance their effects, but even drug eluting stents still have a risk of restenosis, thrombus formation, and necessary revascularization. Continual advancement in stent design necessitates faster, effective pre-clinical evaluation techniques. Kristen Cardinal, Ph.D., developed the blood vessel …

Encapsulation And Controlled Release Of Rhu-Erythropoietin From Chitosan Biopolymer Nanoparticles, Cody Bulmer

Electronic Thesis and Dissertation Repository

The objective of this research project was to develop a drug delivery system for recombinant human erythropoietin (rHu-EPO), a glycoprotein hormone used in the treatment of renal anaemia and chemotherapy induced anaemia, using the biopolymer chitosan as the base component. Two types of chitosan nanoparticles were produced through ionotropic gelation using flush mixing with either tripolyphosphate (TPP) or carrageenan polymer. Chitosan-TPP and chitosan-carrageenan nanoparticles were generated under a variety of conditions to evaluate the effects of chitosan concentration, chitosan to anion mass ratio and solution pH on the nanoparticle characteristics of particle diameter, surface charge and particle size distribution. A …

Bacterial Cellulose Templates For Nano-Hydroxyapatite Fibre Synthesis, Jordan A. Demello

Electronic Thesis and Dissertation Repository

Guided bone regeneration is a medical procedure which induces in vivo re-growth of bone using membranes and osteopromoting fillers. In this work, bacterial cellulose fibers were isolated and used as a basis for biomimetic hydroxyapatite growth, with the ultimate goal of producing GBR filler materials. Acetobacter xylinum generated BC using various carbon sources. Fibers were treated with phosphoric acid to phosphorylate functional groups and preconditioned with calcium to nucleate the HA. Simulated body fluid (SBF) furthered the growth. Over 14 days, the product was characterized via EDX, SEM, FTIR, and XRD. The effect of media composition, phosphorylation time, pretreatment, and …

A New Tool To Assess The Mechanical Properties Of Bone Due To Collagen Degradation, C. Wynnyckyj, S. Omelon, K. Savage, M. Damani, Debbie Chachra, Marc Grynpas

Debbie Chachra

Current clinical tools for evaluating fracture risk focus only on the mineral phase of bone. However, changes in the collagen matrix may affect bone mechanical properties, increasing fracture risk while remaining undetected by conventional screening methods such as dual energy x-ray absorptiometry (DXA) and quantitative ultrasound (QUS). The mechanical response tissue analyzer (MRTA) is a non-invasive, radiation-free potential clinical tool for evaluating fracture risk. The objectives of this study were two-fold: to investigate the ability of the MRTA to detect changes in mechanical properties of bone as a result of treatment with 1 M potassium hydroxide (KOH) and to evaluate …

Investigation Of A New Material For Heart Valve Tissue Engineering, Claire Brougham, Nian Shen, Allison Cudsworth, Thomas Flanagan, Stefan Jockenhoevel, Fergal O'Brien

Conference Papers

No abstract provided.

Mineralization Potential Of Electrospun Pdo-Hydroxyapatite-Fibrinogen Blended Scaffolds, Isaac Rodriguez, Parthasarathy A. Madurantakam, Jennifer M. Mccool, Scott A. Sell, Hu Yang, Peter C. Moon, Gary L. Bowlin

Biomedical Engineering Publications

The current bone autograft procedure for cleft palate repair presents several disadvantages such as limited availability, additional invasive surgery, and donor site morbidity. The present preliminary study evaluates the mineralization potential of electrospun polydioxanone:nano-hydroxyapatite : fibrinogen (PDO : nHA : Fg) blended scaffolds in different simulated body fluids (SBF). Scaffolds were fabricated by blending PDO : nHA : Fg in the following percent by weight ratios: 100 : 0 : 0, 50 : 25 : 25, 50 : 50 : 0, 50 : 0 : 50, 0 : 0 : 100, and 0 : 50 : 50. Samples were immersed …

The Use Of An In Vitro 3d Melanoma Model To Predict In Vivo Plasmid Transfection Using Electroporation, Benadette Marrero, Richard Heller

Bioelectrics Publications

A large-scale in vitro 3D tumor model was generated to evaluate gene delivery procedures in vivo. This 3D tumor model consists of a "tissue-like" spheroid that provides a micro-environment supportive of melanoma proliferation, allowing cells to behave similarly to cells in vivo. This functional spheroid measures approximately 1 cm in diameter and can be used to effectively evaluate plasmid transfection when testing various electroporation (EP) electrode applicators. In this study, we identified EP conditions that efficiently transfect green fluorescent protein (GFP) and interleukin 15 (IL-15) plasmids into tumor cells residing in the 3D construct. We found that plasmids …

A Preliminary Study On The Potential Of Manuka Honey And Platelet-Rich Plasma In Wound Healing, Scott A. Sell, Patricia S. Wolfe, Andrew J. Spence, Isaac A. Rodriguez, Jennifer M. Mccoll, Rebecca L. Petrella, Koyal Garg, Jeffery J. Ericksen, Gary L. Bowlin

Nursing Faculty Publications

Aim. The purpose of this study was to determine the in vitro response of cells critical to the wound healing process in culture media supplemented with a lyophilized preparation rich in growth factors (PRGF) and Manuka honey. Materials and Methods. This study utilized cell culture media supplemented with PRGF, as well as whole Manuka honey and the medical-grade Medihoney (MH), a Manuka honey product. The response of human fibroblasts (hDF), macrophages, and endothelial cells (hPMEC) was evaluated, with respect to cell proliferation, chemotaxis, collagen matrix production, and angiogenic potential, when subjected to culture with media containing PRGF, MH, Manuka honey, …