Biomedical Engineering and Bioengineering Commons^™

Synthesis Of Multilayered Microparticles For Targeted Drug Delivery, Elizabeth Mercer

Open Access Theses

Microparticles have been shown to be valuable in targeted drug delivery which can lead to an increased dose delivered to a targeted location, reduced patient side effects, and improved patient outcomes. The designed multilayered microparticles have the clinical application to deliver hydrophobic drugs to a targeted area. The composition of the microparticles consists of a poly-lactic acid (PLA) polymer core surrounded by a polymeric shell composed of Poly(lactic-co-glycolic acid)-Poly(ethylene glycol)-Maleimide(PLGA-PEG-Mal). The maleimide promotes conjugation of the collagen binding peptide, SILY. Targeting to type I collagen allows for this microparticle system to attach to exposed collagen in atherosclerotic vessels.

A novel …

Probabilistic Uncertainty Quantification And Experiment Design For Nonlinear Models: Applications In Systems Biology, Vu Cao Duy Thien Dinh

Open Access Dissertations

Despite the ever-increasing interest in understanding biology at the system level, there are several factors that hinder studies and analyses of biological systems. First, unlike systems from other applied fields whose parameters can be effectively identified, biological systems are usually unidentifiable, even in the ideal case when all possible system outputs are known with high accuracy. Second, the presence of multivariate bifurcations often leads the system to behaviors that are completely different in nature. In such cases, system outputs (as function of parameters/inputs) are usually discontinuous or have sharp transitions across domains with different behaviors. Finally, models from systems biology …

Hierarchical Cell Fluid Extracellular Matrix Interaction In Cell Microenvironment, Soham Ghosh

Open Access Dissertations

Hierarchical structural interactions between components of cell microenvironment, the extracellular matrix (ECM), cytoplasm, nucleus and fluid, are important phenomena that decide cell level physiological process and tissue engineering applications. One of those tissue engineering modalities is freezing of biomaterials, important in a wide variety of biomedical applications including cryopreservation and cryosurgeries. In order to design these applications, freezing-induced changes of the cells and tissues and corresponding biophysical mechanisms need to be well understood. Although the effects of freezing on cells in suspension have been extensively studied, the intracellular mechanics of cells embedded in the extracellular matrix (ECM) during freezing are …

Intranuclear Strain Measured By Iterative Warping In Cells Under Mechanical And Osmotic Stress, Jonathan T Henderson

Open Access Dissertations

The nucleus is a membrane bound organelle and regulation center for gene expression in the cell. Mechanical forces transfer to the nucleus directly and indirectly through specific cellular cytoskeletal structures and pathways. There is increasing evidence that the transferred forces to the nucleus orchestrate gene expression activity. Methods to characterize nuclear mechanics typically study isolated cells or cells embedded in 3D gel matrices. Often report only aspect ratio and volume changes, measures that oversimplify the inherent complexity of internal strain patterns. This presents technical challenges to simultaneously observe small scale nuclear mechanics and gene expression levels inside the nuclei of …

Development Of Planar Patch Clamp With Potentiometric Calcium Ion-Selective Electrode, Kul Inn

Open Access Dissertations

Ion channels are proteins in cell lipid bilayer membranes and act as pores which can adopt closed and open states, thus gating the flow of ions in and out of the cell. Patch clamp technology has been the proven standard for fundamental studies of ion channel activities. However, the technique has some basic limitations: low throughput, time consuming nature of its process, need of highly skilled personnel and inability to identify ionic composition of electrophysiological events. Many different materials and fabrication methods have been introduced to replace traditional patch clamp setup to overcome limitations.^ In this dissertation, a planar patch …

Theory For Diffusional Encounters In Heterogeneous Environments And Multivalent Electrolyte Screening Of Charged Interface, Ran Li

Open Access Dissertations

We develop a theory for encounter rates in a three-dimensional system of connected compartments. The model of connected compartments exhibits the length-scale dependent diffusion that is observed in many heterogeneous environments, such as porous catalysts and biological environments. We discovered a dimensionless number that is the dominant scaling variable and obtained, for the first time, an analytical expression for the encounter rate. The new theory generalizes the classic Smoluchowski diffusion limit to the case of heterogeneous environments. The new theory is tested using Brownian dynamics simulations.^ We also experimentally investigated the behavior of multivalent electrolyte near a charged solid-liquid interface. …

Acrolein As A Novel Therapeutic Target For Spinal Cord Injury Induced Neuropathic Pain, Jonghyuck Park

Open Access Dissertations

Despite years of research, post-spinal cord injury (SCI) chronic neuropathic pain remains refractory to treatment and drastically impairs quality of life for SCI victims beyond paralysis. Although inflammation and free radicals contribute to neuropathic pain in SCI, the mechanism is not completely clear. We have recently demonstrated that acrolein, a product and catalyst of lipid peroxidation, induces a vicious cycle of oxidative stress, amplifying its effects and perpetuating oxidative stress and inflammation. In the current study, we have confirmed that acrolein is elevated significantly at least two weeks post-SCI which coincides with the emergence of hyperalgesia (mechanical, cold and thermal). …

Structure-Functionality Relationship Of Collagen Scaffolds For Tissue Engineering, Seungman Park

Open Access Dissertations

Tissue engineering is a promising technology that enables scientists to create artificial organs or replace damaged tissues using animal cells and other components. For successful tissue regeneration, many factors should be taken into account, however, three components are most crucial: cell, scaffold, and soluble factor(s). In order to check the functionality after regeneration of desired tissues, various approaches have been attempted, depending on the physical, biological, and chemical properties of the tissues. Recently, the importance of the extracellular matrix (ECM) microstructure is being considered to be important in this regard. The ECM is closely associated with various functional properties of …

Development Of A Static Bioactive Stent Prototype And Dynamic Aneurysm-On-A-Chip(Tm) Model For The Treatment Of Aneurysms, Lisa M. Reece

Open Access Dissertations

Aneurysms are pockets of blood that collect outside blood vessel walls forming dilatations and leaving arterial walls very prone to rupture. Current treatments include: (1) clipping, and (2) coil embolization, including stent-assisted coiling. While these procedures can be effective, it would be advantageous to design a biologically active stent, modified with magnetic stent coatings, allowing cells to be manipulated to heal the arterial lining. Further, velocity, pressure, and wall shear stresses aid in the disease development of aneurysmal growth, but the shear force mechanisms effecting wound closure is elusive. Due to these factors, there is a definite need to cultivate …

Understanding Preferred Leg Stiffness And Layered Control Strategies For Locomotion, Zhuohua H. Shen

Open Access Dissertations

Despite advancement in the field of robotics, current legged robots still cannot achieve the kind of locomotion stability animals and humans have. In order to develop legged robots with greater stability, we need to better understand general locomotion dynamics and control principles. Here we demonstrate that a mathematical modeling approach could greatly enable the discovery and understanding of general locomotion principles. ^ It is found that animal leg stiffness when scaled by its weight and leg length falls in a narrow region between 7 and 27. Rarely in biology does such a universal preference exist. It is not known completely …

Pixel-Based Absorption Correction For Dual-Tracer Fluorescence Imaging Of Receptor Binding Potential, Stephen C. Kanick, Kenneth M. Tichauer, Jason Gunn, Kimberley S. Samkoe, Brian W. Pogue

Dartmouth Scholarship

Ratiometric approaches to quantifying molecular concentrations have been used for decades in microscopy, but have rarely been exploited in vivo until recently. One dual-tracer approach can utilize an untargeted reference tracer to account for non-specific uptake of a receptor-targeted tracer, and ultimately estimate receptor binding potential quantitatively. However, interpretation of the relative dynamic distribution kinetics is confounded by differences in local tissue absorption at the wavelengths used for each tracer. This study simulated the influence of absorption on fluorescence emission intensity and depth sensitivity at typical near-infrared fluorophore wavelength bands near 700 and 800 nm in mouse skin in order …

A Subject-Specific Multiscale Model Of Transcranial Magnetic Stimulation, Brian Daniel Goodwin

Dissertations (1934 -)

Transcranial magnetic stimulation (TMS) is a neuromodulation technique used to treat a variety of neurological disorders. While many types of neuromodulation therapy are invasive, TMS is an attractive alternative because it is noninvasive and has a very strong safety record. However, clinical use of TMS has preceded a thorough scientific understanding: its mechanisms of action remain elusive, and the spatial extent of modulation is not well understood. We created a subject-specific, multiscale computational model to gain insights into the physiological response during motor cortex TMS. Specifically, we developed an approach that integrates three main components: 1) a high-resolution anatomical MR …

Neuromodulation For Depression: Insights Gained From Neuroimaging And Computational Models, Yagna Pathak

Dissertations (1934 -)

Major depressive disorder (MDD) is a public health concern worldwide, affecting a sixth of the American population. Neuromodulation therapies have been employed to treat severe cases of treatment resistant depression. These procedures attempt to modulate activity in cortical regions that represent nodes in brain circuits believed to be involved in MDD. One challenge in neuromodulation trials has been the difficulty in quantifying outcome variability. We sought to understand the effects of neuromodulation therapies and their sources of variability while adding an objective perspective to assess clinical improvement in neuropsychiatric disorders such as depression. The goal of my dissertation was to …

Within-Socket Myoelectric Prediction Of Continuous Ankle Kinematics For Control Of A Powered Transtibial Prosthesis, Samuel Farmer, M. Barbara Silver-Thorn, Philip A. Voglewede, Scott A. Beardsley

Biomedical Engineering Faculty Research and Publications

Objective. Powered robotic prostheses create a need for natural-feeling user interfaces and robust control schemes. Here, we examined the ability of a nonlinear autoregressive model to continuously map the kinematics of a transtibial prosthesis and electromyographic (EMG) activity recorded within socket to the future estimates of the prosthetic ankle angle in three transtibial amputees. Approach. Model performance was examined across subjects during level treadmill ambulation as a function of the size of the EMG sampling window and the temporal 'prediction' interval between the EMG/kinematic input and the model's estimate of future ankle angle to characterize the trade-off between model error, …

Apparatus And Method For Remote Assessment And Therapy Management In Medical Devices Via Interface Systems, Jeffrey Hargrove, Robert M. Ford, Thomas B. Johnson

Mechanical Engineering Patents

A remote medical assessment and therapy management apparatus comprising a center user interface, a center computer coupleable with the center user interface. The center computer displays information via the center user interface for use in developing a therapeutic prescription and receives therapeutic control inputs from a user. A remote device includes a medical diagnostic instrument for acquiring biophysical data from a patient, a medical therapeutic instrument that provides a therapy to the patient, and a remote computer that receives diagnostic signals from the diagnostic instrument and transmits therapeutic control signals to the therapeutic instrument. A network interface is connected between …

Carboxymethylcellulose Hydrogels Support Central Nervous System-Derived Tumor-Cell Chemotactic Migration: Comparison With Conventional Extracellular Matrix Macromolecules, Tanya Singh, Chandrasekhar Kothapalli, Devika Varma, Steven B. Nicoll, Maribel Vazquez

Publications and Research

The local microenvironment plays an important role in maintaining the dynamics of the extracellular matrix and the cell-extracellular matrix relationship. The extracellular matrix is a complex network of macromolecules with distinct mechanical and biochemical characteristics. Disruptions in extracellular matrix homeostasis are associated with the onset of cancer. The extracellular matrix becomes highly disorganized, and the cell-matrix relationship changes, resulting in altered cell-signaling processes and metastasis. Medulloblastoma is one of the most common malignant pediatric brain tumors in the United States. In order to gain a better understanding of the interplay between cell-extracellular matrix interactions and cell-migratory responses in tumors, eight …

Breast Cancer Detection Using Interferometric Music: Experimental And Numerical Assessment, Giuseppe Ruvio, Raffaele Solimene, Antonio Cuccaro, Domenico Gaetano, Jacinta Browne, Max Ammann

Articles

Purpose: In microwave breast cancer detection, it is often beneficial to arrange sensors in close proximity to the breast. The resultant coupling generally changes the antenna response. As an a priori characterization of the radio frequency system becomes difficult, this can lead to severe degradation of the detection efficacy. The purpose of this paper is to demonstrate the advantages of adopting an interferometric multiple signal classification (I-MUSIC) approach due to its limited dependence from a priori information on the antenna. The performance of I-MUSIC detection was measured in terms of signal-to-clutter ratio (SCR), signal-to-mean ratio (SMR), and spatial displacement (SD) …

Cutaneous Electrode Positioning, Jeffrey Hargrove, Susan R. Briggs

Mechanical Engineering Patents

A device and method for positioning a cutaneous electrode for delivery of electrical stimulation to a subject's head. A harness is worn on a subject's head with a first band of the harness worn in a closed loop around the subject's head and around a desired contact location on the subject's head. A tensioning strap of the harness is worn across the desired contact location and connected at spaced-apart attachment locations of the strap to spaced-apart attachment locations of the harness such that an electrode disposed over the desired contact location on the subject's head is held in place by …

A Collagen‐Glycosaminoglycan‐Fibrin Scaffold For Heart Valve Tissue Engineering Applications, Claire Brougham, Stefan Jockenhoevel, Thomas Flanagan, Fergal O'Brien

Conference Papers

The field of heart valve biology and tissue engineering a heart valve continue to expand. The presentatio ns at this meeting reflect the advances made in both areas due to the multi-disciplinary approach taken by many laboratories.

Monitoring Micelle Formation In Mixtures Of Linear And Foldon-Capped Polypeptides With Light Scattering Spectroscopy, Janna Mino, John P. Gavin, Michael G. Price, Kiril Streletzky, Nolan Holland

Undergraduate Research Posters 2014

Elastin-like polypeptide (ELP) polymers are ideal for producing environmentally responsive micellar systems because they exhibit a transition from being water-soluble at low temperatures to phase-separated at high temperatures. For application development of drug delivery vehicles and biosensing nanoparticles, it is important to prepare spherical micelles of controlled diameter and shape. Since at a given salt concentration, the headgroup area for each foldon should be constant, the size of the micelles is expected to be proportional to the volume of the linear ELP available per foldon headgroup. Therefore, adding linear ELPs to a system of ELP-foldon should result in changes of …