Stairs and curbs often present as an exhausting environmental barrier for individuals with bilateral cerebral palsy (CP) due to their lower limb motor impairments. Indeed, performance in stair-climbing in this population has a higher correlation with disruption of mobility than walking. Community members affected by CP consider impaired mobility a...
Each neuron in the primary motor cortex (M1) is like a musician in an orchestra, contributing to a larger harmony under the constraint of a “neural manifold”—a geometric score describing the correlated signals produced by the neural musicians that drive movement. Despite the widespread recognition of the importance of M1...
Ankle sprains are the most common musculoskeletal injury. After an ankle sprain, about 40% of individuals develop Chronic Ankle Instability (CAI), resulting in recurrent sprains, the ankle giving way, or feelings of instability. Most sprains occur due to excess inversion of the ankle. Frontal-plane ankle stiffness quantifies the ankle’s ability...
Bio-integrated electronics with advanced monitoring capabilities have garnered considerable interest as a means of expanding patient care beyond traditional hospital and clinic settings. These mechanically soft microsystems, many of which are bioresorbable and wireless, have the potential to replace bulky, rigid, and wired medical technologies by matching or exceeding their...
The physical structure of chromatin has recently emerged as a key contributor to genome regulation and cellular function. Chromatin packing dictates the conformation of the 2-meter-long DNA polymer within the ~10 μm cell nucleus. This conformation can influence gene function by regulating the accessibility of molecular regulators to DNA, altering...
Wireless power strategies are critical to system level implementation of bio-integrated devices. To achieve mechanically robust, manufacturable systems, batteries are often integrated as an on-board power source to support sensing, wireless communication and signal conditioning. Unfortunately, most sources of battery power use hazardous and environmentally harmful materials, which frustrate incorporation...
Cancer has long been the second-leading cause of death in the United States and represents the leading cause of death in midlife (age 40-60). While the prognosis for many cancers has vastly improved over the last thirty years, many cancers remain elusive due to the late-onset of symptoms, the specific...
Nucleic acid therapeutics can be drug molecules with high programmability, minimal off-target effects, and the capability to address “undruggable” targets for diseases. In addition, each time a new drug is needed, one needs to only change the sequence as opposed to finding an entirely new structure. One nucleic acid type...
Before initiating a walking movement, the central nervous system forms a motor plan, a set of motor commands predicted to accomplish task-specific goals. To be effective, motor plans must be continually updated to consider an ever-changing external environment. Despite being an inherent part of walking, how the nervous system adapts...
The current view in neuroscience holds that the brain, together with its sensory and motor structures and the environment, form a closed-loop system – a sensorimotor loop – in which the brain receives information from the environment and converts it into a motor response while simultaneously making predictions about future...
Vimentin intermediate filaments (VIFs) provide mechanical integrity to cells and serve as markers of tissue origin and cell differentiation. Several non-mechanical roles for vimentin have recently been reported, including regulation of key pathways that control cell growth, cell signaling, and cell motility. Here, I present the role of vimentin in...
Shoulder (glenohumeral joint) osteoarthritis causes pain, limits daily activities, and frequently requires joint replacement surgery. In shoulder osteoarthritis, the glenoid bone surface erodes in one of two ways: symmetrically (concentric deformity) or asymmetrically (eccentric deformity). Shoulder replacements in patients with eccentric deformities fail and require additional, revision surgery more often...
Chromatin is the biological material that packages our genetic information. In humans, 2 meters of linear DNA is compacted into an approximately 6 μm nucleus. Our DNA is transcribed into RNA, which is then translated into proteins. Cellular phenotype, the composite of all cellular functions, is defined by the entire...
Persons with spinal cord injuries can use state-of-the-art brain-computer interfaces to control robotic arms. Despite this high-tech solution, their movements are slow and imprecise, much like those made by individuals who have lost proprioception, the sense of body position and movement. Intracortical microstimulation (ICMS) used to reactivate neural circuits in...
Polymer and polymer/ceramic composites known as bone cements are commonly used in musculoskeletal reconstructive surgeries where bone tissue fixation, reinforcement, or void filling may be needed. Polymethylmethacrylate, PMMA, was the initial (and currently only) FDA-approved bone cement for bone-void filling applications yet faces many inherent material-based challenges that impacts its...
Myoelectric pattern recognition-based upper limb prostheses measure electromyographic (EMG) signals from the residual limb and learn to identify muscle activity patterns that correspond to intended gestures. To train an accurate pattern recognition controller, it is essential that the training signals typify signals measured in real-world scenarios. When these conditions are...
Bioelectronic devices at the biotic/abiotic interface face a number of key challenges that include device degradation when exposed to biological fluid, their elicited immune response due to mechanical mismatch, and poor signal transduction. Organic electronic materials and their devices, such as organic electrochemical transistors (OECTs) address these shortcomings. They can...
In environments ranging from natural ecosystems to living organisms, small molecule signals and nanoscale forces communicate important information regarding chemical contamination and pollution, pathogenesis, and physical stressors. As these stimuli are often well below detection limits for our own senses, we depend on biosensing technologies to monitorthem. Many biosensors operate...
Islet transplantation is a therapy in which insulin-producing beta (β) islet cells are infusedinto the liver via the portal vein to restore glycemic control. This therapy is beneficial for patients
suffering from chronic pancreatitis or type I diabetes. However, islet transplantation is not widely
implemented due to the instant blood-mediated...
Proprioception, or the sense of one’s body in space, provides critical feedback that the brain usesto generate controlled movements. When proprioceptive feedback is lost, people find it difficult
to perform even basic motor tasks. Despite its importance, proprioceptive coding of single
neurons in the cuneate nucleus (CN), the most peripheral...
Over the past decade, wearables have become pervasive in our lives. Healthcare wearables like a smartwatch continuously monitor personal health status and provide personalized feedback to motivate progress towards medically recommended goals. While present set of on-body electronics empowers users to visualize health status outside of clinic spaces, its traditionally...
Nanocarriers, structures with at least one dimension on the nanoscale (1-1000 nm), have been engineered for delivery of various cargoes. The shape and flexibility of nanocarriers are important parameters that influence their biological performance. Self-assembling polymeric filamentous nanocarriers, known as filomicelles (FM), are of great interest to nanomedicine due to...
Nanocarriers are drug delivery vehicles that have at least one dimension at the nanoscale (10-9 m). Engineering the nanocarrier surface is a strategy for targeting drug delivery to specific cell types to enhance efficacy and minimize side effects. A useful analogy is to consider how the chassis of an automotive...
Nanocarriers as structures with at least one dimension in the nanometer scale are capable of loading small molecule therapeutics that would otherwise have poor bioavailability, non- specific uptake, and off target effects. Polymeric nanocarriers can be modified to tune their chemical and biological behavior to better suit the intended application....
Like many diseases, atherosclerotic cardiovascular disease is driven by the activity of inflammatory cells. Using molecular imaging to target and analyze populations of inflammatory cells is one promising strategy to non-invasively assess atherosclerosis progression. However, current molecular imaging contrast agents are not suited for such targeted imaging applications. Nanomaterial-based strategies...
Nucleic acids such as DNA or RNA of various lengths and structures have a wide scope of functions as therapeutic entities compared to conventional drugs. For instance, native and modified forms of nucleic acids can be used for gene silencing, genome editing, gene replacement, immune system modulation, and theranostics. While...
Humans have a remarkable ability to create stable walking patterns that can resist and recover from perturbations. Unfortunately, this ability is substantially impaired after a stroke, limiting mobility and contributing to a high fall rate. To facilitate gait training during post-stroke rehabilitation, clinicians often incorporate body-weight support (BWS) systems that...
Coordinated movement relies on the precise and controlled activation of populations of motor units, which convert the commands of the nervous system into muscle forces. Motor unit firing patterns are often nonlinear and generated through the response to a combination of ionotropic excitatory and inhibitory commands, as well as metabotropic...
Soft materials in nature are formed through programmed self-assembly of biomolecules to create complex architectures and optimized physical properties. It is therefore a key challenge in biomaterials science and engineering to understand the principles that govern the structure and properties of such materials, and the interactions between their different components....
Optical microscopy is one of the most ubiquitous tools for functional imaging of biological phenomena. While relatively non-destructive to living organisms, light microscopy’s spatial resolution is diffraction limited, restricting the minimum resolvable features. On the other hand, high resolution techniques such as electron microscopy or STORM, have several orders of...
Transplantation is necessary and often the only viable treatment for many forms of end stage organ failure. While advances in immunosuppressive therapies have facilitated largely blocking acute rejection, 5-10 year post-transplant attrition rates have not significantly improved in the past 30 years. The predominant antigen facilitating the alloimmune response is...
Bio-inspired materials have a distinct advantage over other materials by virtue of their mimicry of nature’s own products, which have been subjected to the inimitable tests of time and evolutionary pressure. Here we have taken instruction from natural nanostructures that are ubiquitous across the animal kingdom, namely high-density lipoproteins (HDL)....
The last decade has witnessed a rapid transformation in our understanding of the structure of chromatin, the nuclear complex of DNA and its structural proteins. While, barring mutations, the DNA sequence in each cell of the human body is the same, it is the structure of the chromatin complex that...
The shoulder is the most mobile joint in the human body, allowing for the execution of complex and athletic tasks. Unfortunately, such expansive mobility comes at a cost. The shoulder is prone to instability, or painful symptoms associated with increased humeral head translation, and dislocation. To prevent dislocations and maintain...
Nanoparticles are nanometer scale (1-1000 nm) structures capable of encapsulating a diverse range of cargoes. Encapsulation of a cargo can drastically alter its pharmacokinetics, cytotoxicity, and biodistribution while allowing for informed and rational design of the nanoparticle itself. Poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS) is an amphiphilic diblock co-polymer able to self-assemble...
Found in 1-2% of the population, bicuspid aortic valve (BAV) is the most common congenital cardiovascular disease and is associated with increased risk of aortic valve dysfunction and aortic disease. Current treatment is focused on surgical intervention either after the development of symptomatic aortic stenosis/regurgitation or aortic diameter thresholds. However,...
Radiofrequency ablation is a minimally-invasive treatment method that aims to destroy undesired tissue by exposing it to alternating current in the 100 kHz to 800 kHz frequency range and heating it until it is destroyed via coagulative necrosis. Ablation treatment is gaining momentum especially in cancer research, where the undesired...
The dynamics of human joints are fundamental characteristic of the human motor system, and altered joint impedance can hinder mobility. Individuals with transtibial amputation typically experience slower and energetically costly gait, while individuals with chronic stroke experience persisting gait deficits arising from spasticity, hypertonia and paresis. Investigating joint impedance of...
A one-time, unilateral injury to the developing brain can interrupt the typical process of development and result in motor impairments that evolve over the course of the whole life-span. The timing of injury relative to neural development has implications for the continued refinement of the nervous system and the descending...
Everyday tasks, such as putting on a jacket or reaching up to a shelf, often become more challenging for older adults. These tasks rely on the ability to generate three-dimensional torques about the shoulder and to adapt these torques across activities. Shoulder strength and muscle coordination impact shoulder torque production,...
4D Flow MRI is a phase-contrast magnetic resonance imaging method that enables direct measurement of velocities in three orthogonal directions throughout the heartbeat. This permits direct quantification of hemodynamic parameters, including flow, mean velocity, peak velocity, and pulsatility, for individual cerebral vessels. Despite ongoing research into neurovascular applications of 4D...
Fluorescence microscopy has become a widely used tool in many research areas. However, its spatial resolution, limited to 250 nm by the diffraction limit of light, has restricted direct observation of details of ultrastructural biology. In recent years, spectroscopic single-molecule localization microscopy (sSMLM), one of super-resolution imaging techniques, has been...
We rely on the properties of our skeletal muscles to traverse our world, interact with objects, and complete everyday tasks. The macroscopic properties of muscles that endow us with these abilities arise from the material properties of muscle fibers and the surrounding extracellular matrix (ECM), as well as how they...
Decisions in naturalistic environments usually feature delayed and uncertain outcomes that can only be reached after a sequence of actions are performed. For example, canonical stalking and pursuit strategies used by terrestrial predators often involve stages of concealment, pauses where the predator remains motionless, and high speed chase sequences. The...
In nature, materials with complex architectures are formed through hierarchical self-assembly. Therefore, the study and design of hierarchically assembling materials is important in producing materials that mimic biological structures and is a key challenge in biomaterials science and engineering. In articular cartilage, hierarchical assembly of extracellular matrix (ECM) components provides...
Single-molecule localization microscopy (SMLM) has significantly stimulated the development of methods to quantitatively visualize and characterize biomolecules in vitro and in situ. SMLM is a class of super-resolution microscopy (SRM) techniques, which exploits the “on-off” switching of individual fluorescent molecules to estimate their location with nanometer precision and offers spatial...
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and associated with increased risk for ischemic stroke and mortality. While the risk of stroke has been shown to be reduced with the use of oral anticoagulants like Warfarin, these medications are predictably linked with an increased risk of bleeding, and...
The goal of the work reported here was to answer two important questions with regards to LTVV use for patients with ARDS: 1) How do we measure adoption? and 2) What are the drivers of provider adoption? To this end, I have demonstrated the influence of patient height, hypoxemia severity,...
Atrial fibrillation (AF) is the most common arrhythmia in adults in the United States. Despite its prevalence, the etiology of AF and its adverse effects are not completely understood, which has made treatment of AF difficult. However, left atrial (LA) fibrosis is associated with worsening and propagating AF. Additionally, research...
Label-free assays, and particularly those based on the combination of mass spectroscopy with surface chemistries, enable high-throughput experiments of a broad range of reactions. However, these methods can still require the incorporation of functional groups that allow immobilization of reactants and products to surfaces prior to analysis. In this thesis,...