Xerox Engineering Research Fellows
2020 Research Opportunities
Research Project #1: Hydrogel Culture Environments for Regenerative Medicine Applications
We can interrogate and take advantage of the critical interactions between cells and extracellular matrix (ECM) to create bioactive materials capable of controlling cell function and tissue evolution. To determine the requirements of the microenvironment, we utilize hydrogels easily modified with respect to mechanical integrity, adhesive peptides, ECM molecules, degradability, and incorporation of drugs, to direct cellular differentiation through a variety of mechanisms.
In particular, we are interested in utilizing hydrogel microenvironments to direct encapsulated mesenchymal stem cell (adult stem cell) function for applications in musculoskeletal tissue engineering. A thorough understanding of how material properties effect cell differentiation and tissue evolution is essential to tailor ‘instructive materials’ to direct cell function.
Research Project #2: Targeted Polymer Therapeutics to Overcome Drug Delivery Barriers
Conventional small molecule drugs and large macromolecular drugs have significant and distinctly different delivery barriers. For example, small molecule drugs, such as the chemotherapeutic doxorubicin, is highly hydrophobic, thus administration requires toxic cosolvents to aid blood solubility. Macromolecular drugs, on the other hand, suffer from enzymatic degradation and inactivation, difficulty in targeting to the appropriate cells and transversing the cell membrane, and often become degraded intracellularly once endocytosed. We are investigating polymer-drug complexes or polymer-drug conjugates to overcome these barriers and modulate drug delivery.
Research Project: Viscoelastic Heating of Soft Biological Tissues
Back pain is the leading cause of disability globally and the second most common cause of doctors’ visits. Despite extensive research efforts, the underlying mechanism of back pain has not been fully elucidated. The intervertebral disc (IVD) is a viscoelastic tissue that provides flexibility to the spinal column and acts as a shock absorber in the spine. When viscoelastic materials like IVD are cyclically loaded, they dissipate energy as heat. Thus, daily movements of the vertebral column intermittently deform the IVD and could increase disc temperature through viscoelastic heating. This temperature elevation has the potential to influence cell function, alter enzyme kinetics, drive cell death, and potentially induce nociception in innervating neurons within the IVD. Our work to date has focused on investigating the capacity of IVD to increase in temperature due to viscoelastic heating in vitro. According to our findings, the IVD can experience a measurable temperature rise (up to 2.5° C) under cyclic loading. This magnitude of temperature rise has physiological relevance as degenerative IVD tissue has been shown to produce a sensitization of nociceptive neurons that can spontaneously fire with a maximum response at just 1° C above normal body temperature. Thus, our results suggest that viscoelastic heating of IVD could interact with sensitized neurons in the degenerative IVD to play a role in back pain. Current work in this project is aimed at determining how viscoelastic heating of the disc may affect tissue structure and integrity, in addition to investigating the role of viscoelastic heating in pathologies affecting other soft biological tissues.
Research Project #1: Biomedical Optics for Breast Cancer Detection and Therapy Monitoring
The overall goals of this project in Professor Choe's laboratory are to assess and improve the capabilities of diffuse optical technology in breast cancer therapy monitoring and detection. In clinical measurements of human breasts with tumor, we focus on identifying functional parameters measurable with diffuse optics, which can serve as early indicators of therapy efficacy. Using a preclinical animal model, we study the metabolic mechanism of varied responses to therapy seen in the clinic, and investigate new therapeutic drugs and interventions. The students will have opportunities to participate in various aspects of research: instrumentation construction and characterization, data analysis algorithm development, preclinical experiments, and/or clinical experiments.
Research Project #2: Diffuse Optical Imaging for Non-Invasive Deep Tissue Monitoring of Bone Healing
Achieving effective revascularization is critical for successful healing of bone grafts or fractures. While various tissue engineering and regenerative medicine strategies have been proposed and tested, most revascularization assessment is performed using methods requiring destruction/sacrifice of samples. Diffuse optical imaging can quantify hemodynamic parameters of deep-tissue in vivo samples non-invasively, allowing longitudinal monitoring of bone graft vascularization process. The project will focus on development of imaging methods for in vivo preclinical experiments, which will give students exposure to various aspects of research: instrumentation construction and characterization, data analysis algorithm development, preclinical experiments, and collaboration with experts in tissue engineering field (Professor Benoit laboratory).
Professor Diane Dalecki
Department of Electrical and Computer Engineering and Biomedical Engineering
Research Project: Biomedical Ultrasound
The primary goals of Professor Dalecki’s laboratory are to advance novel diagnostic ultrasound techniques, and to discover new therapeutic applications of ultrasound in medicine and biology. For this project, students will work towards developing new ultrasound technologies for the field of tissue engineering and regenerative medicine. Specifically, students will investigate the effects of ultrasound on extracellular matrix proteins and cell functions that are key for engineering artificial 3D tissues and enhancing wound repair. Students will develop skills in acoustic field calibration, signal processing, cellular and tissue preparation procedures, cell and extracellular matrix biology, and ultrasound physics. The research is highly multidisciplinary and spans the fields of biomedical ultrasound, acoustics, medical imaging, cell and tissue engineering, and biomechanics.
Research Project: Mechanobiology of Embryonic Tissue Development
How the embryo develops tendons and ligaments that transmit forces throughout the adult body is yet to be understood. The Kuo Lab harnesses the powerful tools that engineers have developed for study of synthetic materials and utilizes them to analyze living embryonic tissues. With this novel approach, our goal is to understand the mechanobiology of load-bearing tissue development, and use this knowledge to inform innovative strategies for engineering new tendons and ligaments from stem cells. Projects range from developing living embryo models, to interrogating the mechanical microenvironment of embryonic tissues, to fabricating custom-designed biomaterials and mechanical loading bioreactors to mechanoregulate tissue engineering and regeneration.
Research Project: 3-Dimensional Hydrogel Systems to Regulate Stem Cell Differentiation
Stem cell function, such as differentiation and the regeneration of new tissues, can be controlled by the mechanical and biochemical properties of the surrounding extracellular matrix (engineered or natural). Less understood is what specific combination of such cues is required to elicit a desired response that leads to formation of a normal, functional tissue. Furthermore, why certain stem cells respond to some cues and not to others is minimally understood. Projects in the Kuo Lab are focused on developing and tailoring 3-dimensional hydrogel culture systems to 1) identify combinations of mechanical and biochemical cues that can instruct stem cell differentiation toward specific musculoskeletal tissue lineages, and 2) understand what specific characteristics of stem cells play critical roles in these responses.
Research Project: Mechano-transduction of the Inner Ear Sensory Organ
We study the mechano-transduction of the inner ear. In the cochlea, mammalian hearing organ, mechanical stimuli (sounds) are encoded to neural signals. The identification of mechanical properties of cochlear sensory cells and tissues is crucial to better understand how we hear (or fail to hear). Students will participate in measuring mechanical responses of artificial and biological micro structures in a micro-fluidic device. Through this project, students will learn how the principles of acoustics, fluid dynamics, solid mechanics and vibrations are applied to micro-mechanical experiments with biological tissues. Students will gain experiences with vibration measurements, imaging and data acquisition devices. Students will be trained to handle experimental animals and assist in preparing tissues for experiments.
Research Project: Auditory Neuroscience Lab
We combine neurophysiological, behavioral, and computational modeling techniques towards our goal of understanding neural mechanisms underlying the perception of complex sounds. Most of our work is focused on hearing in listeners with normal hearing ability. We are also interested in applying the results from our laboratory to the design of physiologically based signal-processing strategies to aid listeners with hearing loss.
We are currently studying the following specific problems:
- Detection of acoustic signals in background noise
- Coding of complex sounds, such as speech, by fluctuations in neural responses
- Signal processing to enhance fluctuation cues for listeners with hearing loss
- Neural sensitivity to fast frequency transitions
These problems are of interest because they involve tasks at which the healthy auditory system excels, but they are situations that can present great difficulty for listeners with hearing loss. We study the psychophysical limits of ability in these tasks, and we also study the neural coding and processing of these sounds using stimuli matched to those of our behavioral studies.
Computational modeling helps bridge the gap between our behavioral and physiological studies. For example, using computational models derived from neural population recordings, we make predictions of behavioral abilities that can be directly compared to actual behavioral results. The cues and mechanisms used by our computational models can be manipulated to test different hypotheses for neural coding and processing.
By identifying the cues involved in the detection of signals in noise and fluctuations of signals, our goal is to direct novel strategies for signal processors to preserve, restore, or enhance these cues for listeners with hearing loss.
Research Project #1: Assessing Disease Progression and Treatment Efficacy for Parkinson's and Huntington's Diseases Using Data Analytics on Body Worn Sensors
Parkinson's and Huntington's diseases are characterized by debilitating motion irregularities: such as tremors, unsteady gain, involuntary movements, and lack of coordination. This project seeks to use analytics on data captures from minimally obtrusive sensors worn at multiple points on the body for detecting and classifying motion irregularities, for quantifying the durations of such symptoms, and for characterizing the efficacy of medication in mitigating these symptoms.
Research Project #2: Deep Learning and Data Analytics for Ophthalmic Diagnosis
Common systemic diseases, such as diabetes and hypertension, affect the body's vasculature. These vascular changes can be visualized and assessed using fundus photography (FP) and wide-field fluorescein angiography (FA), a process that involves injecting dye and taking images of it passing through the retinal blood vessels. In this project, we aim to develop an automated computer-aided method for retinal image analysis and ophthalmic diagnosis. We focus on applying deep learning techniques to detect retinal vessels in FP and FA images. We also analyze clinical data for to assess disease progression and treatment and to assist physicians
Research Project #1:Engineering Scarless Repair of Tendon Injuries
We are pioneering regenerative treatments to injuries to flexor tendons in zone II of the hand, which are among the most difficult injuries for surgeons to repair. Restoration of function during healing is often impaired due to the formation of debilitating adhesions and the incidence of repair rupture typically necessitates additional surgery. Our research focuses on the mechanobiology regulating tendon healing with the goal of manipulating target pathways and processes to develop clinically translatable biological therapies to improve outcomes of tendon healing. Our approach uses genetic mouse models of zone II flexor tendon injury and novel in vitro platforms to uncover the cellular and molecular mechanisms of fibrotic healing, and innovative biomaterials approaches for drug delivery to target candidate pathologic pathways. A specific focus of this fellowship involves novel in vitro microphysiological systems of inflammation and fibrosis in acute and chronic tendon pathologies.
Research Project #2: Bone Regeneration and Infection Management using 3D Printed Scaffolds
Our lab is developing alternative fabrication technologies of spacers that can enhance the reproducibility of sustained release of antibiotics over a sufficient period to ensure eradication of bone infections and osteomyelitis, and potentially eliminate the need for the costly reconstruction procedures. Our hypothesis is that image-guided 3D printing of antibiotic-loaded, osteoinductive ceramic scaffolds can be effective in a single-stage reconstruction of infected nonunions with segmental bone loss.
Specifically, our work has led to the development of innovative strategies for adapting low- temperature 3D printing technology to fabricate osteoconductive calcium phosphate (CaP) scaffolds for applications in preclinical models of bone regeneration and infection. This technology has translational potential in medical image-guided reconstruction of massive bone loss in scenarios involving extremity bone and craniomaxillofacial trauma or infections. Some specific foci of research for this fellowship include adapting different modalities of low-temperature 3D printing of antibiotic-laden CaP scaffolds for sustained bactericidal delivery, and stem cell strategies to vitalize and vascularize 3D printed scaffolds for bone regeneration in craniofacial bones, including mandible and jaw, and long bones of the extremities, including radius and femur.