1998 — 2003 |
Costanzo, Francesco |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Career: Sculptured Thin Films: Non-Linear Nanomechanics and Homogenization For a New Class of Engineered Thin Film Composites With Evolving Nanostructure @ Pennsylvania State Univ University Park
Nanomechanics is employed to characterize the nonlinear thermo-mechanical properties of sculptured thin films. Also, a homogenization theory of sculptured thin films is formulated to analytically and computationally derive the effective constitutive and evolution equations of these nano- engineered systems. Software and computer-based courseware is developed to simulate the experimental activity used in the identification of the thermo-mechanical properties of homogeneous as well as composite materials. The project contributes to the improvement of fabrication and life prediction techniques for a new class of composite thin films with promising applications on electroluminescent devices, optical sensor technology, micro-sieves for entrapment of viruses or for growth of biological tissues on surfaces of biological and on-biological origin.
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2014 — 2017 |
Costanzo, Francesco Huang, Tony Jun (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Probing Mechanical Biomarkers With Microacoustofluidics: a Fluid-Structure Interaction Approach @ Pennsylvania State Univ University Park
PI: Costanzo, Francesco Proposal Number: 1438126
The objective of the proposed work is to study the hydrodynamic interactions between deformable microparticles, and specifically between a micro-bubble and a cell. The idea is to create a micro-bubble using a laser next to the cell, and then use acoustic methods to obtain information about the mechanical properties of the cell. Such information would be used mainly for diagnostic purposes, but also for therapeutic purposes. This idea that a cell's mechanical properties can be used as a biomarker for pathogenic processes is currently being used to diagnose malaria, and there is some evidence that mechanical biomarkers may be used to diagnose cancer. The proposed work could lead directly from fluid dynamics research to applications. The proposed research will lead to more effective, cheaper, and faster cell-based on-chip diagnostic and therapeutic devices. As such, this research can have a major impact on public health world-wide.
Cellular mechanical properties have been found to be valuable indicators for pathogenesis and pathophysiology. This has led to the identification of a new class of biomarkers: mechanical biomarkers that offer some advantages over traditional biochemical biomarkers. While a number of mechanical biomarker-based microfluidic devices have already been proposed in the literature, the full potential of mechanical biomarkers in microfluidic-based diagnostics and therapeutics has yet to be revealed. One reason is the fact that no techniques are currently available for the quantitative assessment of cell deformability in relation to the forces acting on them. Current approaches for estimating the radiation forces on objects in streaming flows are based on classical solutions for idealized geometries (typically spheres) and small deformation of elastic inclusions in the flow. The proposed research will use computational techniques based on the immersed finite element method to advance knowledge in these areas. The goal is to relate cell deformability to the hydrodynamic forces imposed on a cell or on a group of cells in a microfluidic device. The validation of the proposed computational framework will be done against experiments with cancer cells in an opto-thermally-generated and acoustically-activated surface bubbles microfluidic device. The co-PIs propose to involve undergraduate students in research and to leverage already existing initiatives at Penn State in order to reach underrepresented minority students: the Women in Engineering Program and the Multicultural Engineering Program.
This award by the Fluid Dynamics Program of the CBET Division is co-funded by the Instrument Development for Biological Research (IDBR) Program of the Division of Biological Infrastructure.
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2015 — 2018 |
Yang, Jian (co-PI) [⬀] Costanzo, Francesco |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Computational Prediction of Mechanical and Transport Response Evolution in Degrading Porous Scaffolds @ Pennsylvania State Univ University Park
Restoring living tissue functionality via tissue engineering is crucial for transformative advances in medicine. Tissue engineering materials must be biocompatible and often biodegradable in a controlled manner. For example, severed peripheral nerves can regrow, but new projections must be properly nourished and guided via tissue scaffolds. Scaffolds must have the right morphology for cell growth, the right transport properties for nourishing cells, and the right mechanical properties to stay compliant and integral during degradation and tissue regeneration. Biodegradable scaffolds are appealing because they need not be surgically removed; but they are effective only if degradation is synchronized with nerve regrowth. This is but one of many examples illustrating the extraordinary challenges in tissue engineering. This award will yield a multi-scale approach based on physics, mathematics, polymer chemistry, and image analysis to predict and interrogate evolving transport and mechanical properties of porous polymeric scaffolds during programmed enzymatic degradation. The contribution of the project to the advancement of mechanics is a new methodology to model, and thus understand, the behavior of multi-functional materials with evolving microstructure like those in nerve tissue engineering. An educational component is included to attract underrepresented minorities to engineering via level-appropriate workshops on applications of mechanics in neuroscience, and by involving undergraduates in the creation of coursework for courses in brain biomechanics.
Biodegradable tissue engineering systems are deformable chemically-reacting porous mixtures with complex fluid-structure interaction. The project integrates specific existing averaging techniques with an original fluid-structure interaction approach to determine the coupled mechanical and transport properties of degrading porous polymer networks subjected to large deformation and mechanical loadings. The model system of relevance to the project is crosslinked urethane-doped polyester, a promising scaffold material for nerve regeneration with highly controllable porosity. This material will be modeled as a random polymer network. Samples will be analyzed via electron microscopy to quantify the network's morphology. Microscopic-level transport and mechanical properties will be determined via a statistical characterization of the polymer network structure. This process will define microstructurally accurate representative volume elements whose evolution can then be analyzed via a novel finite element fluid-structure interaction-based homogenization procedure for evolving microstructure due to degradation. This numerical scheme will yield effective mechanical and transport properties at the mesoscale as a function of degradation. A crucial advancement in mechanics is the framing of the homogenization problem as a fluid-structure interaction problem, by extending the immersed finite element method (a state-of-the-art fluid-structure interaction computational approach) to account for fluid flow through bodies with evolving microstructure. The project includes experiments to validate predicted properties. Material samples and full-scale scaffold at different stages of degradation will be characterized in terms of morphology, elastic moduli, and diffusivity, and these properties compared to corresponding numerical estimates.
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2017 — 2020 |
Costanzo, Francesco Gluckman, Bruce (co-PI) [⬀] Drew, Patrick (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Imaging and Modeling Fluid Mechanics of Metabolite Transport in the Brain Interstitium @ Pennsylvania State Univ University Park
In the course of its normal function, the brain produces toxic substances that accumulate and are transported from the space between brain cells. If these substances are not cleared, their accumulation is thought to yield crippling results such as Alzheimer's disease and migraines. The mechanics of this clearance is poorly understood, so this research project aim to study and characterize this process. Experimental techniques and computational approaches are being combined to produce a predictive clearance model based on fundamental mechanics principles of fluid flow and diffusion. The experimental study is being conducted in vivo, which will allow for a physiologically-relevant match between brain function and the corresponding deformation of brain tissue and the associated flow of the fluid in-between cells. This study is relevant for advancing the state of the art in neurophysiology and for future development of therapeutic interventions, both pharmacological and surgical, for addressing pathologies including Alzheimer's disease, hydrocephalus, and migraine. This project has an educational component aiming at training graduate and undergraduate students in advanced neuroscience research and in biomedical engineering. Specifically, the researchers and developing and offering a level-appropriate laboratory and computational projects for undergraduates with a focus on the merging of experimental techniques and mechanics in neuroscience.
This project focuses on delivering the first mechanics-based model of the effects of neurovasculature coupling on transport in the brain. A theoretical and computational framework is being created to model multiple concurrent transport mechanisms in a computational framework that integrates empirical in vivo observations of the brain micromechanical neurovascular response to chosen stimuli. The biomedical problem motivating the proposed research is the comparative assessment of convective and diffusive mechanisms for toxic metabolite clearance from the brain interstitium. Buildup of these compounds can be strongly neurotoxic and can trigger neuronal functional instabilities with severe, if not lethal, consequences---from spreading depolarization to epilepsy to Alzheimer's disease to mental illnesses. While vital for brain function, metabolite transport and clearance remains poorly understood. The specific project goals are: 1) To model brain tissue as a deformable porous medium with embedded vasculature, and to apply a numerical scheme developed by the PIs for predicting transport driven by blood vasodilation; 2) To identify sets of relevant physiological conditions from the experiments, and, from these, to define corresponding metabolite transport boundary value problems. Pulsation (heart-gated blood vessel dilation) and functional hyperemia (neurovascular coupling driven vessel dilation) will be considered. Anatomical, material, and loading parameters will be inferred using in vivo two-photon microscopy in the brains of living mice with cranial windows. Fluorescence-based digital image correlation will deliver microscale deformation maps of brain tissue. Fluid flow in the brain will be visualized by infusing fluorescent dyes; 3) To numerically solve the problems in goal 2 to determine interstitial fluid flow and metabolite transport through deformable tissue with convection and diffusion as concurrent mechanisms. Ranges of physiological conditions and constitutive parameters are being tested, and fluid-structure interaction between tissue and fluid-filled paravascular space are being explicitly modeled. The high selectivity of the blood-brain barrier remains a major challenge in developing effective drug delivery methods for brain cancer, dementia, spreading depolarization, and epilepsy. By focusing on metabolite transport in brain, this research project will contribute to advancing pharmacological and surgical therapies for many brain pathologies.
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2020 — 2021 |
Costanzo, Francesco Craven, Brent Manning, Keefe B [⬀] Simon, Scott D |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Modeling of Acute Ischemic Stroke For Improving Mechanical Thrombectomy @ Pennsylvania State University-Univ Park
Summary For the estimated 700,000 acute ischemic strokes (AIS) that occur each year in the United States, new stent retriever devices have shown an increase in recanalization of occluded cerebral arteries. However, over 15% of thromboemboli are still unable to be cleared and another 17% of patients die within 90 days despite successful recanalization. To date, there is little understanding of the upstream thrombosis and embolization processes that lead to AIS and why some thromboemboli are successfully removed and others are not. To better understand the entire progression of AIS, we will develop computational models of the upstream thrombosis, thrombus embolization, lodging and adhesion in the cerebral vasculature, and removal via applied forces from a thrombectomy device. These models will be validated with ex vivo mock circulatory flow loops that enable real-time tracking of thrombus growth and embolization and for AIS occlusion to be simulated in physiologically accurate scenarios. Furthermore, patient-specific anatomy and blood chemistry will be used. The results of these studies will provide insight to AIS occlusion but provide an opportunity to improve overall patient outcomes.
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