Xerox Engineering Research Fellows
2018 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 in Tendon
Tendinopathies including tendinitis and tennis elbow are painful, chronic conditions typically associated with tendon overuse. In-vivostudies of horse flexor tendons have measured temperatures greater than 45⁰ C during activity as a result of viscoelastic dissipation. In the human Achilles tendon, application of thermodynamic theory to in-vivo stress-strain data suggests that temperatures could exceed 41⁰ C during running. Since these temperatures are known to trigger thermal nociceptors, induce fibroblast necrosis and alter the extracellular matrix, intra-tendinous viscoelastic hyperthermia could play a key role in tendon pathology. Importantly, since tendinopathy is known to increase viscoelastic dissipation in tendons, this condition may involve a feedback process through which heat-induced damage renders the tendon more susceptible to further heating and accelerated degeneration. Nevertheless, viscoelastic heating has not been studied in a controlled, ex-vivo environment allowing for evaluation of the effects of pathology on heat generation. Our long-term goal is to compare viscoelastic heating in healthy and pathological tendons. As a first step in this process, we are currently 1) optimizing our ex-vivo testing system; and 2) conducting experiments aimed at characterizing location-dependent viscoelastic heating in healthy tendons (i.e., comparing heating in the tendon midsubstance and tendon-bone insertion). The findings of this study will establish viscoelastic heating as a significant factor in tendon pathology and motivate novel therapies aimed at reducing intra-tendinous hyperthermia.
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 Graft Vascularization
Achieving effective revascularization is critical for successful integration of bone graft. While various tissue engineering 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).
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 #1: 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 #2: Regulation of Stem Cell Differentiation
It is well established that stem cell function, such as differentiation and the regeneration of new tissues, can be controlled by the application of exogenous cues. 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 1) identifying combinations of mechanical and biochemical cues that can be applied exogenously to direct stem cell differentiation toward specific musculoskeletal tissue lineages, and 2) understanding what specific characteristics of stem cells play critical roles in these responses.
Research Project: Measurement of Mechanical Properties of the Inner Ear Sensory Organ
We study the mechano-transduction of the inner ear. The cochlea, the mammalian hearing organ, turns mechanical stimuli (sound) into 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). To measure the mechanical properties, we need to apply calibrated pressures in the order of mPa and measure displacements in nanometers at the frequency of up to tens of kHz. Students will participate in measuring mechanical responses of artificial and biological micro structures in a micro-fluidic chamber system. 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.