A. James Clark School of Engineering
Permanent URI for this communityhttp://hdl.handle.net/1903/1654
The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
Browse
50 results
Search Results
Item Blueprinting Self-Assembled Soft Matter: An `Easy' Approach to Advanced Material Synthesis in Drug Delivery and Wound Healing(2010) Dowling, Matthew Burke; Raghavan, Srinivasa R; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)From Jello to mayonnaise to silly putty to biological cells, our world is replete with "soft matter" - materials that behave as soft, deformable solids or highly viscoelastic liquids. Living systems, in particular, can be thought of as extremely sophisticated `soft' machines, with each cellular unit representing a touchstone for the functional potential of soft materials built via self-assembly. Drawing inspiration from biology, we blueprint soft biomaterial designs which rely upon self-assembly to achieve enhanced functionality. As opposed to complex synthesis schemes often used to develop improved biomaterials, we take an `easy' approach by allowing relatively simple molecules orchestrate themselves into advanced machines. In this dissertation, we describe four separate "soft" systems, all constructed by self-assembly of amphiphilic molecules under designed and/or triggered conditions in aqueous media. These systems revolve around a common theme: the structural tandem of (1) vesicles and (2) biopolymers, and the resulting interactions between the two. Our blueprints show promise in several important biomedical applications including controlled drug release, tissue engineering, and wound care. In the first part of this study, we blueprint a biopolymer gel that entraps pH-sensitive vesicles. The vesicles are formed by the self-assembly of a single-tailed fatty acid surfactant. We show that the gel has pH-responsive properties imparted upon it via the embedded vesicle nanostructures. Specifically, when the gel is brought in contact with a high pH buffer, the diffusion of buffer into the gel disrupts the vesicles and transforms them into micelles. Accordingly, a vesicle-micelle front moves through the gel, and this can be visually seen by a difference in color. The disruption of vesicles means that their encapsulated solutes are released into the bulk gel, and in turn these solutes can rapidly diffuse out of the gel. Thus, we can use pH to tune the release rate of model drug molecules from these vesicle-loaded gels into the external solution. In the second part, we have blueprinted hybrid biopolymer capsules containing drug-loaded vesicles by means of a one-step self-assembly process. These capsules are called "motherships" as each unit features a larger container, the polymer capsule, carrying a payload of smaller vesicular containers, or "babyships," within its lumen. These motherships are self-assembled via electrostatic interactions between oppositely charged polymers/surfactants at the interface of the droplet. Capsule size is simply dictated by drop size, and capsules of sizes 200-5000 µm are produced here. Lipid vesicles, i.e. the babyships, are retained inside motherships due to the diffusional barrier created by the capsule shell. The added transport barrier provided by the vesicle bilayer in addition to the capsule shell provides sustained drug release from the motherships. Furthermore, this one-step drop method allows for the rapid synthesis of soft materials exhibiting structural features over a hierarchy of length scales, from nano-, to micro- to macro-. Thirdly, we have therapeutically functionalized biopolymer films by simply passing a solution of vesicles over the film surface. We deposit films of an associating biopolymer onto patterned solid substrates. Subsequently, these polymer films are able to spontaneously capture therapeutically-loaded vesicles from solution; this is demonstrated both for surfactant as well as lipid vesicles (liposomes). Importantly, it is verified that the vesicles are intact - this is shown both by direct visualization of captured vesicles (via optical and cryo-transmission electron microscopy) as well as through the capture and subsequent disruption of drug filled vesicles. Such therapeutically-functionalized films may be of use in the treatment of chronic wounds and burns. Lastly, we have demonstrated that the addition of a certain biopolymer transforms a suspension of whole blood into a gel. This blueprint is inspired from previous research in our group on the biopolymer-induced gelation of vesicles, which are structurally similar to cells. Upon mixture with heparinized human whole blood, this amphilic biopolymer rapidly forms into an "artificial clot." These mixtures have highly elastic character, with the mixtures able to hold their own weight upon vial inversion. Moreover, the biopolymer shows significant hemorrhage-controlling efficacy in animal injury models. Such biopolymer-cell gelation processes are shown to be reversed via introduction of an amphiphilic supramolecule, thus introducing the novel concept of the "revesible hemostat." Such a hemostatic functionality may be of large and unprecedented use in clinical the treatment of problematic hemorrhage both in trauma and routine surgeries.Item SCAFFOLD DESIGN PARAMETERS TO STIMULATE THE OSTEOGENIC SIGNAL EXPRESSION FOR BONE TISSUE ENGINEERING APPLICATIONS(2010) KIM, KYOBUM; Fisher, John P; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The fundamental components of bone tissue engineering are (a) progenitor cells which subsequently express tissue matrix, (b) scaffolds which can act as temporary frameworks to support bone growth, and (c) growth factors to induce osteoblast regeneration. A variety of growth factors are involved during the differentiation cascade and these chemical and biological signals dynamically interact with cell populations to facilitate the differentiation. Therefore, enhanced expression of endogenous growth factor genes might facilitate abundant existence of growth factors in the surrounding microenvironment, stimulate the osteogenic differentiation of progenitor cell population, and finally induce bone regeneration. This work is focused on the augmentation of osteogenic signal expressions to stimulate the downstream differentiation of transplanted bone marrow stromal cells (BMSCs) population through the optimization of a variety of properties of three dimensional (3D) biodegradable poly(propylene fumarate) (PPF) scaffold. Changes in the microenvironment of cell population would affect the responses of localized cell population and the manipulated scaffold properties might be associated with induction of endogenous osteogenic signal expressions. First, the effect of cell-to-cell paracrine signaling distance, which can by modulated by initial cell seeding density, on the osteogenic signal expressions and osteoblastic differentiation of BMSCs on 2D PPF disks was investigated. Next, in order to investigate the improvement of the 3D macroporous PPF scaffold by the incorporation with nanoparticle filler materials, PPF/hydroxyapatite (HA) nanocomposite scaffolds were fabricated. The effect of HA content and initial cell seeding density on the osteogenic signal expression in 3D porous system was then determined. Finally, the incorporation of diethyl dumarate (DEF) with PPF was tested based on the photocrosslinking characteristics of PPF/DEF composite material with increased mechanical properties. The effect of two scaffold design parameters including the stiffness by modulating the DEF content as well as the pore size of porous scaffold on the signal expression and downstream osteoblastic differentiation was investigated. In addition, the feasibility of PPPF/DEF materials for stereolithographical fabrication was also tested in this work. Controlling these construction parameters to optimize engineered bone substitutes could affect various cellular functions of attachment, proliferation, signal expression, and differentiation. This research provided the insight of stimulation of the expression of target endogenous genes to induce the osteogenic differentiation and bone regeneration as well as the fabrication of improved bone substitute implant materials which is clinically applicable.Item OPTIMAL CONTROL OF OBJECTS ON THE MICRO- AND NANO-SCALE BY ELECTROKINETIC AND ELECTROMAGNETIC MANIPULATION: FOR BIO-SAMPLE PREPARATION, QUANTUM INFORMATION DEVICES AND MAGNETIC DRUG DELIVERY(2010) Probst, Roland; Shapiro, Benjamin; Aerospace Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In this thesis I show achievements for precision feedback control of objects inside micro-fluidic systems and for magnetically guided ferrofluids. Essentially, this is about doing flow control, but flow control on the microscale, and further even to nanoscale accuracy, to precisely and robustly manipulate micro and nano-objects (i.e. cells and quantum dots). Target applications include methods to miniaturize the operations of a biological laboratory (lab-on-a-chip), i.e. presenting pathogens to on-chip sensing cells or extracting cells from messy bio-samples such as saliva, urine, or blood; as well as non-biological applications such as deterministically placing quantum dots on photonic crystals to make multi-dot quantum information systems. The particles are steered by creating an electrokinetic fluid flow that carries all the particles from where they are to where they should be at each time step. The control loop comprises sensing, computation, and actuation to steer particles along trajectories. Particle locations are identified in real-time by an optical system and transferred to a control algorithm that then determines the electrode voltages necessary to create a flow field to carry all the particles to their next desired locations. The process repeats at the next time instant. I address following aspects of this technology. First I explain control and vision algorithms for steering single and multiple particles, and show extensions of these algorithms for steering in three dimensional (3D) spaces. Then I show algorithms for calculating power minimum paths for steering multiple particles in actuation constrained environments. With this microfluidic system I steer biological cells and nano particles (quantum dots) to nano meter precision. In the last part of the thesis I develop and experimentally demonstrate two dimensional (2D) manipulation of a single droplet of ferrofluid by feedback control of 4 external electromagnets, with a view towards enabling feedback control of magnetic drug delivery to reach deeper tumors in the long term. To this end, I developed and experimentally demonstrated an optimal control algorithm to effectively manipulate a single ferrofluid droplet by magnetic feedback control. This algorithm was explicitly designed to address the nonlinear and cross-coupled nature of dynamic magnetic actuation and to best exploit available electromagnetic forces for the applications of magnetic drug delivery.Item Experimental Characterization of Vascular Tissue Viscoelasticity with Emphasis on Elastin's Role(2010) Shahmirzadi, Danial; Hsieh, Adam; Mechanical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Elucidating how cardiovascular biomechanics is regulated during health and disease is critical for developing diagnostic and therapeutic methods. The extracellular matrix of cardiovascular tissue is composed of multiple fibrillar networks embedded in an amorphous ground substance and has been found to reveal time-dependent mechanical behavior. Given the multiscale nature of tissue biomechanics, an accurate description of cardiovascular biomechanics can be obtained only when microstructural morphology is characterized and put together in correlation with tissue-scale mechanics. This study constitutes the initial steps toward a full description of cardiovascular tissue biomechanics by examining two fundamental questions: How does the elastin microstructure change with tissue-level deformations? And how does the extracellular matrix composition affect tissue biomechanics? The outcome of this dissertation is believed to contribute to the field of cardiovascular tissue biomechanics by addressing some of the fundamental existing questions therein. Assessing alterations in microstructural morphology requires quantified measures which can be challenging given the complex, local and interconnected conformations of tissue structural components embedded in the extracellular matrix. In this study, new image-based methods for quantification of tissue microstructure were developed and examined on aortic tissue under different deformation states. Although in their infancy stages of development, the methods yielded encouraging results consistent with existing perceptions of tissue deformation. Changes in microstructure were investigated by examining histological images of deformed and undeformed tissues. The observations shed light on roles of elastin network in regulating tissue deformation. The viscoelastic behavior of specimens was studied using native, collagen-denatured, and elastin-isolated aortic tissues. The stress-relaxation responses of specimens provide insight into the significance of extracellular matrix composition on tissue biomechanics and how the tissue hydration affects the relaxation behavior. The responses were approximated by traditional spring-dashpot models and the results were interpreted in regards to microstructural composition.Item A biophysical evaluation of cell-substrate interactions during spreading, migration and neuron differentiation(2010) Norman, Leann Lynn; Aranda-Espinoza, Helim; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The development of engineered scaffolds has become a popular current avenue to treat numerous traumas and disease. In order to optimize the efficiency of these treatments, it is necessary to have a more thorough understanding of how cells interact with their substrate and how these interactions directly affect cellular behavior. Cell spreading is a critical component of numerous biological phenomena, including embryonic development, cancer metastasis, immune response, and wound healing. Along with spreading, cell adhesion and migration are all strongly dependent on the interactions between the cell and its substrate. Cell-substrate interactions can affect critical cellular mechanisms including internal cellular signaling, protein synthesis, differentiation, and replication and also influence the magnitude of adherence and motility. In an effort to better understand cell-substrate interactions we characterize the initial stages of cell spreading and blebbing using cell-substrate specific microscopy techniques, and identify the effects of cytoskeletal disruption and membrane modification on surface interactions and spreading. We identify that blebs appear after a sharp change in cellular tension, such as following rapid cell-substrate detachment with trypsin. An increased lag phase of spreading appears with increased blebbing; however, blebbing can be tuned by supplying the cell with more time to perform plasma membrane recycling. We developed software algorithms to detect individual bleb dynamics from TIRF and IRM images, and characterize three types of bleb-adhesion behaviors. Overall, we show that blebs initially create the first adhesion sites for the cell during spreading; however, their continuous protrusion and retraction events contribute to the slow spreading period prior to fast growth. In addition, we identify the elastic modulus of the rat cortex and characterize a polyacrylamide gel system that evaluates the effects of substrate stiffness on cortical outgrowth. Remarkably, we illustrate that cortical neuron differentiation and outgrowth are insensitive to substrate stiffness, and observe only morphological differences between laminin versus PDL-coated substrates. Together, this research identifies cell-specific behaviors critical to spreading and migration. The thorough evaluations of spreading and migration behavior presented here contribute to the understanding of critical cellular phenomena and suggest potential therapeutic targets for treatment of cardiovascular disease and neurological disorders.Item An Optimal Control Model for Human Postural Regulation(2010) Li, Yao; Levine, William S; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Human upright stance is inherently unstable without a balance control scheme. Many biological behaviors are likely to be optimal with respect to some performance measure that involves energy. It is reasonable to believe that the human is (unconsciously) optimizing some performance measure as he regulates his balance posture. In experimental studies, a notable feature of postural control is a small constant sway. Specifically, there is greater sway than would occur with a linear feedback control without delay. A second notable feature of the human postural control is that the response to perturbations varies with their amplitude. Small disturbances produce motion only at the ankles with the hip and knee angles unchanging. Large perturbation evoke ankle and hip angular movement only. Still larger perturbation result in movement of all three joint angles. Inspired by these features, a biomechanical model resembling human balance control is proposed. The proposed model consists of three main components which are the body dynamics, a sensory estimator for delay and disturbance, and an optimal nonlinear control scheme providing minimum required corrective response. The human body is modeled as a multiple segment inverted pendulum in the sagittal plane and controlled by ankle and hip joint torques. A series of nonlinear optimal control problems are devised as mathematical models of human postural control during quiet standing. Several performance criteria that are high even orders in the body state or functions of these states (such as joint angle, Center of Pressure COP or Center of Mass COM) and quadratic in the joint control are utilized. This objective function provides a trade-off between the allowed deviations of the position from its nominal value and the neuromuscular energy required to correct for these deviations. Note that this performance measure reduces the actuator energy used by penalizing small postural errors very lightly. By using the Model Predictive Control (MPC) technique, the discrete-time approximation to each of these problems can be converted into a nonlinear programming problem and then solved by optimization methods. The solution gives a control scheme that agrees with the main features of the joint kinematics and its coordination process. The derived model is simulated for different scenarios to validate and test the performance of the proposed postural control architecture.Item Noninvasive neural decoding of overt and covert hand movement(2010) Bradberry, Trent Jason; Contreras-Vidal, José L.; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)It is generally assumed that the signal-to-noise ratio and information content of neural data acquired noninvasively via magnetoencephalography (MEG) or scalp electroencephalography (EEG) are insufficient to extract detailed information about natural, multi-joint movements of the upper limb. If valid, this assumption could severely limit the practical usage of noninvasive signals in brain-computer interface (BCI) systems aimed at continuous complex control of arm-like prostheses for movement impaired persons. Fortunately this dissertation research casts doubt on the veracity of this assumption by extracting continuous hand kinematics from MEG signals collected during a 2D center-out drawing task (Bradberry et al. 2009, NeuroImage, 47:1691-700) and from EEG signals collected during a 3D center-out reaching task (Bradberry et al. 2010, Journal of Neuroscience, 30:3432-7). In both studies, multiple regression was performed to find a matrix that mapped past and current neural data from multiple sensors to current hand kinematic data (velocity). A novel method was subsequently devised that incorporated the weights of the mapping matrix and the standardized low resolution electromagnetic tomography (sLORETA) software to reveal that the brain sources that encoded hand kinematics in the MEG and EEG studies were corroborated by more traditional studies that required averaging across trials and/or subjects. Encouraged by the favorable results of these off-line decoding studies, a BCI system was developed for on-line decoding of covert movement intentions that provided users with real-time visual feedback of the decoder output. Users were asked to use only their thoughts to move a cursor to acquire one of four targets on a computer screen. With only one training session, subjects were able to accomplish this task. The promising results of this dissertation research significantly advance the state-of-the-art in noninvasive BCI systems.Item Lipid-Hydrogel Nanoparticles: Synthesis Methods and Characterization(2009) Hong, Jennifer S.; Raghavan, Srinivasa R; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation focuses on the directed self-assembly of nanoscale soft matter particles using methods based on liposome-templating. Nanoscale liposomes, nano-sized hydrogel particles ("nanogels"), and hybrids of the two have enormous potential as carriers in drug delivery and nanotoxicity studies, and as nanovials for enzyme encapsulation and single molecule studies. Our goal is to develop assembly methods that produce stable nanogels or hybrid lipid-polymer nanoparticles, using liposomes as size and shape templates. First we describe a bulk method that employs liposomes to template relatively monodisperse nanogels composed of the biopolymer, alginate, which is a favorable material for nanogel formation because it uses a gentle ionic crosslinking mechanism that is suitable for the encapsulation of cells and biomolecules. Liposomes encapsulating sodium alginate are suspended in aqueous buffer containing calcium chloride, and thermal permeabilization of the lipid membrane facilitates transmembrane diffusion of Ca2+ ions from the surrounding buffer into the intraliposomal space, ionically crosslinking the liposome core. Subsequent lipid removal results in bare calcium alginate nanogels with a size distribution consistent with that of their liposome template. The second part of our study investigates the potential for microfluidic-directed formation of lipid-alginate hybrid nanoparticles by adapting the above bulk self-assembly procedure within a microfluidic device. Specifically we investigated the size control of alginate nanogel self-assembly under different flow conditions and concentrations. Finally, we investigate the microfluidic directed self-assembly of lipid-polymer hybrid nanoparticles, using phospholipids and an N-isopropylacrylamide monomer as the liposome and hydrogel precursors, respectively. Microfluidic hydrodynamic focusing is used to control the convective-diffusive mixing of the two miscible nanoparticle precursor solutions to form nanoscale vesicles with encapsulated hydrogel precursor. The encapsulated hydrogel precursor is polymerized off-chip and the resultant hybrid nanoparticle size distributions are highly monodisperse and precisely controlled across a broad range relevant to the targeted delivery and controlled release of encapsulated therapeutic agents. Given the ability to modify liposome size and surface properties by altering the lipid components and the many polymers of current interest for nanoparticle synthesis, this approach could be adapted for a variety of hybrid nanoparticle systems.Item Parallelization of Non-Rigid Image Registration(2008) Philip, Mathew; Shekhar, Raj; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Non-rigid image registration finds use in a wide range of medical applications ranging from diagnostics to minimally invasive image-guided interventions. Automatic non-rigid image registration algorithms are computationally intensive in that they can take hours to register two images. Although hierarchical volume subdivision-based algorithms are inherently faster than other non-rigid registration algorithms, they can still take a long time to register two images. We show a parallel implementation of one such previously reported and well tested algorithm on a cluster of thirty two processors which reduces the registration time from hours to a few minutes. Mutual information (MI) is one of the most commonly used image similarity measures used in medical image registration and also in the mentioned algorithm. In addition to parallel implementation, we propose a new concept based on bit-slicing to accelerate computation of MI on the cluster and, more generally, on any parallel computing platform such as the Graphics processor units (GPUs). GPUs are becoming increasingly common for general purpose computing in the area of medical imaging as they can execute algorithms faster by leveraging the parallel processing power they offer. However, the standard implementation of MI does not map well to the GPU architecture, leading earlier investigators to compute only an inexact version of MI on the GPU to achieve speedup. The bit-slicing technique we have proposed enables us to demonstrate an exact implementation of MI on the GPU without adversely affecting the speedup.Item Automated quantification and classification of human kidney microstructures obtained by optical coherence tomography(2009) Li, Qian; Chen, Yu; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Optical coherence tomography (OCT) is a rapidly emerging imaging modality that can non-invasively provide cross-sectional, high-resolution images of tissue morphology such as kidney in situ and in real-time. Because the viability of a donor kidney is closely correlated with its tubular morphology, and a large amount of image datasets are expected when using OCT to scan the entire kidney, it is necessary to develop automated image analysis methods to quantify the spatially-resolved morphometric parameters such as tubular diameter, and to classify various microstructures. In this study, we imaged the human kidney in vitro, quantified the diameters of hollow structures such as blood vessels and uriniferous tubules, and classified those structures automatically. The quantification accuracy was validated. This work can enable studies to determine the clinical utility of OCT for kidney imaging, as well as studies to evaluate kidney morphology as a biomarker for assessing kidney's viability prior to transplantation.