Biomaterials / Biomechanics Research Overview

Bluestein, Danny

Professor

Danny.Bluestein@sunysb.edu

Summary : Despite major progress, cardiovascular diseases remain the leading cause of death in the western world. One of the major culprits in cardiovascular disease and in devices designed to treat or restore impaired cardiovascular function is the non-physiologic flow pattern that enhances the hemostatic response mainly through platelet activation. Platelets have long been regarded as the preeminent cell involved in physiologic hemostasis and pathologic thrombosis. An innovative technique for measuring flow induced platelet activation has been developed, and its utility demonstrated in experiments conducted in recirculation devices (models of arterial stenosis, Left Ventricular Assist Device (LVAD), and mechanical heart valves). The mechanisms by which the non-physiologic flow patterns induce platelet activation and generate free emboli, that enhance the risk of cardioembolic stroke, was demonstrated in vivo with mechanical heart valves implanted in the sheep model. The results of this research will aid in elucidating physical forces that regulate cellular function in flowing blood, and may be applied to improve the design of blood recirculating devices and to develop more potent drugs for treating cardiovascular diseases.

Chen, Weiliam

Associate Professor

Weiliam.Chen@sunysb.edu

Summary : Our research is focused on the application of biocompatible/biodegradable natural carbohydrates to address various clinically relevant biomedical problems including wound repair, cerebral aneurysm, arteriovenous malformation, abdominal aortic aneurysm endoleak and controlled delivery of therapeutic agents (small molecules, proteins and DNA) through interdisciplinary research efforts. Localized application provides the maximum efficacies of therapeutic agents while minimizing their undesirable effects. Other efforts are targeted towards ophthalmic issues and enhancing the biological responses of polymeric medical devices.

Clark, Richard

Professor

Richard.Clark@SUNYSB.EDU

Summary : Our laboratory focuses on the design and development of bioactive peptides and 3-D complex extracellular matrices (ECM) that will enhance soft tissue repair and regeneration. Peptides are assayed for biologic activity in vitro and in vivo for their ability to protect tissue cells and organs from injury, stimulate tissue cell migration and proliferation, and modulate stem cell and tissue cell differentiation. The ECM constructs tethered with bioactive peptides are analyzed for their physical, chemical and immunologic properties by such modalities as goniometry for hydrophilicity, static and dynamic stress and strain for viscolastic material properties, atomic force microscopy for Young’s elastic moduli and surface topography; HPLC, mass spectroscopy, gel permeation chromatography and gel electrophoresis for chemical analysis; and fluorescence immunoassays for immunologic epitope mapping. In addition, cell interactions with the 3-D ECM constructs are examined at the transcriptional, protein and functional level as judged by real-time PCR, DNA microarray analyses, Western blots, proteomics, quantitative fluorescence microscopy, and cell viability, migration and proliferation assays. Special in vitro systems have been created to quantify sprout angiogenesis, epithelial sheet migration and neurite axon extension. Bioactive peptides and engineered ECM containing peptide biomimetics will also be tested in a variety of animal models and hopefully enter into clinical trials. This robust array of bioactive peptides and 3-D ECM constructs will provide new therapies for soft tissue injury and disease.

Dhundale, Anil

Research Assistant Professor

Anil.Dhundale@sunysb.edu

Summary : My interests are in commercialization of technology, i.e.- translating research discoveries into useable commercial products. These products can be therapeutics to treat disease, diagnostics for identifying or classifying disease, or tools for researchers to use. But in addition all technology based products include Information Technologies, Clean/Alternative Energy, etc. Currently I manage the Stony Brook Technology Business Incubators Program from an office at the Long Island High Technology Incubator (www.LIHTI.org). This position is to assist academic researchers to start companies and mentor established small technology businesses, all with a goal to translate discoveries into novel products and services. The Stony Brook campus and our partner research institutions on Long Island have a long established, highly successful, culture of invention. There is also an extensive Economic Development network (http://www.sunysb.edu/ecodev/) with many individuals that have and continue to guide a broad range of technologies from discovery through development. Our goal for economic development is to create and retain high technology jobs and have positive economic impact in the Long Island region.

Einav, Shmuel

Professor

seinav@sunysb.edu

Summary : The primary role of this laboratory is to study basic physiological flow phenomena, both experimentally and numerically, as well as cellular and tissue engineering as applied to the vascular system. and to suggest ways of improving the functioning of cells, tissues and organs in the body. These physiological flows include blood flow in the heart, blood flow in arteries, veins and the microcirculation, air flow in the respiratory airways, and urine flow in the kidney and urethra. This laboratory simulates systems through the use of computers, assisting life scientists to better understand physiological functions without having to rely entirely on living systems as experimental models. The use of mathematical analysis helps minimize animal experimentation. Other projects are the investigation of hemodynamics as a regulator of vascular biology, the mathematical modeling of the dynamic response of mammalian cells, the role of flow and the associated shear stress on vascular endothelial biology, prosthetic circulatory devices and the tissue engineering of blood vessel substitutes. The laboratory is also engaged in the evaluation of critical conditions that lead to failure of biological organs, such as the heart and the coronary circulation, failure of circulatory prosthetic devices as stents, heart valves and grafts. To facilitate in vitro and in vivo studies, the laboratory develops new investigative techniques, noninvasive diagnostic methods, and advance, multi-dimensional numerical modeling.

Entcheva, Emilia

Associate Professor

Emilia.Entcheva@sunysb.edu

Summary : The focus of the Cardiac Cell Engineering Laboratory is designing and characterizing heart cell networks and heart tissue in the lab to gain a better understanding of how cardiac cells self-organize and function. We are motivated to provide useful tools for physiomics type of studies, drug, gene and stem cell therapy testing 3D cellular platforms - an experimental setting for validation of computer models of excitable tissue, and ultimately to contribute to strategies for the regeneration of the heart. This research is multidisciplinary in nature and involves a spectrum of experimental molecular and cell biology procedures, along with the application of design concepts from electrical, optical, mechanical and chemical engineering to create the enabling technology for our studies. New imaging modalities, image processing algorithms and computer modeling are essential complementary tools developed and applied by our team. Key research areas include: 1) optical mapping of excitation; 2) advanced signal and imageprocessing; 3) cardiac cell and tissue engineering; 4) unraveling the mechanisms of cardiac arrhythmias.

Frame, Molly

Associate Professor & Undergraduate Program Director

Mary.Frame@sunysb.edu

Summary : " Our emerging understanding of oxygen delivery to the tissues is that the blood flow within the smallest arterioles is tightly organized within repeating networks across the tissue. Central to this new paradigm are the concepts of vascular communication between the beginning and end of the network (via gap junctions), and its relation to flow sensing by the vascular endothelium. Our work has shown that different types of microvascular flow patterns can be triggered by direct stimulation of the focal adhesions (alpha-v-beta-3 integrins, i.e., wound healing), compared to adenosine (i.e., metabolic change), compared to nitric oxide (i.e., inflammation), hence we can control the flow patterns. Among the goals of this work are in vitro construction of transplantable microvascular networks, using bionanotechnology to create the sturdy scaffolding, and verification of nanofabricated drug delivery units within the vasculature. To this end, equally important are mechanotransduction of the physical forces associated with flow change (i.e., wall shear stress), the pharmacologic signal transduction systems involved (which guide drug discovery and intervention), and the molecular basis for the committed step that ensures healthy flow delivery. Our work employs computational modeling of the fluid mechanics, the physiology of arteriolar network blood flow (in vivo and in vitro), and precise genomic manipulation of key proteins in healthy and vascular disease states. "

Hadjiargyrou, Michael

Associate Professor

Michael.Hadjiargyrou@sunysb.edu

Summary : The overall goal of this laboratory is to implement innovative approaches for engineering new musculoskeletal tissue utilizing knowledge derived from molecular/cellular biology and biomaterials. More specifically, we are actively involved in understanding the molecular mechanisms that underlie the wound healing process. The repair of a fractured bone is a complex biological event that essentially recapitulates embryonic development and requires the orchestration of a number of different cell types undergoing proliferation, migration, adhesion and differentiation, all under the direct control of a host of different genes. Understanding the temporal and spatial expression of these genes during the progression of a healing callus will ultimately enable us to comprehend the essential processes of inflammation, chondrogenesis, ossification, and remodeling. The latest methods in molecular/cellular biology are applied in the pursuit of gene discovery, gene structure and function analysis, expression studies and functional perturbations. By identifying and studying genes that play essential roles during the healing process, we hypothesize that this knowledge will facilitate a greater understanding in our ability to elucidate the process of bone development and regeneration and identify ideal gene candidates for possible therapeutic intervention via the use of biomaterials.

Hainfeld, James F.

hainfeld@bnl.gov

Summary : James Hainfeld develops organometallic cluster compounds to be used as high resolution molecular labels. These heavy metal clusters are covalently attached to peptides, antibodies, other proteins, nucleic acids, carbohydrates or lipids to map sites of macromolecules or complexes for visualization in the Scanning Transmission Electron Microscope (STEM). Such clusters have been useful in studying the proteasome, pyruvate dehydrogenase enzyme complex, actin filaments, viruses, blood clotting components, nuclear proteins, and other structures. Use of clusters in anomalous X-ray scattering or for isomorphous replacements is being investigated also. Gold, platinum, palladium, silver, iridium, and other metal clusters have been synthesized. Recently, gold clusters having Nickel-NTA for binding 6x-His tagged proteins, gold-liposomes, gold-cluster-ATP, and giant platinum clusters have been studied. Dr. Hainfeld also founded Nanoprobes, Inc., a bio-nanotechnology biotech company, and serves as the CEO. Nanoprobes researches and develops organometallic nanoparticles for use in biomedical and material science applications. for more information see: www.biology.bnl.gov/stem/stem.html and www.nanoprobes.com

Jesty, Jolyon

Professor

JJesty@mail.som.sunysb.edu

Summary : Jo Jesty's research is done in collaboration with colleagues in the Department of Applied Mathematics and Statistics and the Department of Biomedical Engineering. His main interest is how the control mechanisms of blood coagulation interact to minimize the response of the system to low stimulus levels; in other words, the prevention of the abnormal responses that cause thrombosis. This involves a two-pronged approach of experimental kinetic studies in parallel with mathematical analysis and numerical simulation of the control systems involved. Jesty's particular focus is the controls that operate in the initiation of coagulation, in which two inhibitors are involved, along with three positive feedbacks. Additionally, a recent collaborative project concerns the effect of prosthetic heart valves on platelet function, and particularly the ways in which they damage platelets. Jesty has published in the areas of both biochemistry and applied mathematics in Biochemistry, Proceedings of the National Academy of Sciences, and many other journals. He is also an associate editor of the journal Haemostasis.

Judex, Stefan

Associate Professor

Stefan.Judex@sunysb.edu

Summary : Research in this laboratory focuses on the identification of precise parameters that define skeletal tissue quantity and quality and their perturbation to applied physical stimuli. To this end, state of the art imaging techniques (e.g., microCT or synchrotron infrared spectroscopy) are combined with molecular (e.g., RT-PCR), genetic (e.g., QTL), and engineering techniques (e.g., finite element modeling) to determine genes, molecules, forces, as well as chemical and structural matrix properties. An example for a recent study includes the demonstration that extremely small amplitude oscillatory motions (~ 100µm), inducing negligible deformation in the matrix, can serve as an anabolic stimulus to osteoblasts in vivo, producing a structure that is mechanical stronger and more efficient to withstand forces. Recent results also indicate that there is not only a genetic basis for bone architecture, but also that the sensitivity of bone tissue to both anabolic and catabolic stimuli is influenced by subtle genetic variations. The identification of the specific chromosomal regions that modulate this differential sensitivity is in progress. Clinically, our studies may lead to the development of effective prophylaxes and interventions for osteoporosis, without side-effects and tailored towards the genetic make-up of an individual.

Kolsky, Kathryn L.

Scientist

kolsky@bnl.gov

Summary : Kathryn Kolsky’s primary research interest is in the development and production of radioisotopes using the BLIP facility, a high-energy charged particle accelerator at Brookhaven National Laboratory. Many of these isotopes have applications in the field of Nuclear Medicine. Of current interest is the development of techniques for the production of no-carrier added tin-117m (an Auger emitter) for tumor therapy. Most malignant tumors express one or more receptor proteins that are absent or subdued in normal cells. Targeting such exclusive proteins with radionuclides to image or treat tumors is a very attractive approach. The targeting moiety most often is an analog of the natural ligand for the receptors. We are developing methods to synthesize Sn-117m labeled precursors that will selectively bind to the estrogen receptor on malignant breast carcinoma, while sparing the surrounding normal tissue.

Lin, Wei

Research Assistant Professor

Wei.Lin@sunysb.edu

Summary : Virtual instrumentation is defined as a layer of software and/or hardware added to a general purpose computer in such a fashion that users can interact with the computer as though it were their own custom-designed traditional electronic instrument. The technology represents a fundamental shift from traditional hardware based instrumentation systems to software based systems by using the up-to-date computing technologies. This will greatly facilitate the commercialization of the technology developed in academic laboratory because it can integrate the prototype system efficiently using commercial available hardware modules and software application. This eliminates the development cycles of traditional prototype development process and any modification to the system can be done through software modification instantly. Thus the time period for the translation of academic developed technology to commercial products will be substantially reduced.

Logan, Jean

Scientist

Summary : Jean Logan has worked in the positron emission tomography (PET) group at BNL since her post-doctoral in theoretical chemistry. Her research interests are primarily the kinetic modeling of data from PET experiments. PET measures radioactivity concentration in tissue after the introduction of a radiotracer. The PET group has developed radiotracers for a number of brain receptors (for example the dopamine D2 receptor, the dopamine transporter, the norepinephrine transporter) and enzymes (monoamine oxidase A and B which occur in the brain as well as in many peripheral organs). Since PET measures the total radiotracer concentration in the tissue it is necessary to separate the tissue accumulation due to functioning receptor etc. from other processes such as tracer delivery via blood flow. She developed a simple technique for analyzing PET data extracting information related to available receptor concentration that is frequently used in PET research today.

Qin, Yi-Xian

Professor

Yi-Xian.Qin@sunysb.edu

Summary : Early diagnostic of osteoporosis allows for accurate prediction of fracture risk and effective options for early treatment of the bone disease. A new ultrasound technology, based on focused transmission and reception of the acoustic signal, has been developed by Dr. Qin and his team which represents the early stages of development of a unique diagnostic tool for the measure of both bone quantity (density) and quality (strength). These data show a strong correlation between non-invasive ultrasonic prediction and micro-CT determined bone mineral density (r>0.9), and significant correlation between ultrasound and bone stiffness (r>0.8). Considering the ease of use, the non-invasive, non-radiation based signal, and the accuracy of the device, this work opens an entirely new avenue for the early diagnosis of metabolic bone diseases.

Rubin, Clinton

Distinguished Professor & Chair

Clinton.Rubin@sunysb.edu

Summary : Encouraging results show that the application of extremely low level strains to animals and humans will increase bone formation, and thus may represent the much sought after "anabolic" stimulus in bone. More than 15 years of research into non-invasive, non-pharmacological intervention to control osteoporosis, was referenced in Dr. Rubin's paper published in the journal Nature (August 9, 2001; 412:603-604). Dr. Rubin's studies suggest that gentle vibrations on a regular basis will help strengthen the bones in osteoporosis sufferers and increase bone formation. In his study, adult female sheep treated with gentle vibration to their hind legs for 20 minutes daily showed almost 35% more bone density. Clinical trials have been completed on post-menopausal women, children with cerebral palsy, and young women with osteoporosis, all with encouraging results. In expanding the research platform into other physiologic systems, current work demonstrates that these low-level signals influence mesenchymal stem cell differentiation, such that their path to adipocytes is suppressed, and markedly reduces adipose tissue.

Sitharaman, Balaji

Assistant Professor

Balaji.Sitharaman@sunysb.edu

Summary : Our laboratory seeks to integrate advances in nanoscience and technology with the biological sciences and clinical medicine to achieve significant advances in simultaneous molecular diagnostics and therapeutics (theragnosis), drug delivery, and bioengineering. Towards these ends, our research interests involve a multidisciplinary approach for the development of functional (electronic, optical, magnetic, or structural) bionanosystems as contrast agents for molecular imaging, as carriers for drug delivery, and as structural scaffolds for tissue engineering. Our current projects capitalize on the unique properties of carbon nanobiomaterials to develop a) advanced contrast agents (CAs) for molecular magnetic resonance imaging (MRI), b) nanocomposites to improve the physical and biological (osteoconduction and osteoinduction) properties of polymer scaffolds for bone tissue engineering and c) non-viral vectors for gene transfection. We have exploited the potential of Gd-based carbon nanostructures: Gd@C60 metallofullerenes (gadofullerenes) and Gd@Ultrashort-tubes (gadonanotubes) as a new generation of advanced CAs for MRI and shown them to have efficacies up to 100 times greater than current clinical CAs. Our recent studies show that they are particularly well suited for passive (magnetic labels for cellular MRI) and active (pH sensitive probes for cancer detection) MRI-based Molecular Imaging. Single-walled carbon nanotubes (SWNTs) have been proposed as the ideal foundation for the next generation of materials due to their excellent mechanical properties. We have dispersed SWNTs and ultra short SWNTs into fumarate-based polymers to form nanocomposite scaffolds that exhibit mechanical properties far superior to the polymers alone and are osteoconductive as well osteoinductive. Our research work involves material synthesis techniques, physico-chemical characterization techniques, tissue culture and in vivo studies.

Strey, Helmut

Associate Professor & Graduate Program Director

Helmut.Strey@sunysb.edu

Summary : Nature's ability to assemble simple molecular building blocks into highly ordered materials, such as those found in cell membranes, cell nuclei, cytoskeleton, cartilage, or bone presents many fascinating and unanswered questions. We are interested in how to tune the interactions of water-soluble building blocks so as to induce their self-assembly into useful microstructures much needed for the next generation of controlled drug delivery, biosensors and DNA sequencing applications. In particular, we are working on long-range ordered polyelectrolyte-surfactant microemulsions that are used as templates for solid nanoporous materials using polymerization and/or cross-linking strategies. Such materials, because of their well-ordered porous structure, will allow more efficient molecular separation and drug delivery. In addition, we are developing biosensors that are based on biopolymer chiral liquid crystals and quantum dot colloidal crystals. In both cases the softness of the systems allows the induction of a strong optical response to external stimuli. Such sensors should be able to quantitatively detect and measure analyte concentrations at hormonal levels.

Thanos, Panayotis (Peter) K.

Assisant Professor

thanos@bnl.gov

Summary : "Gene therapy and dopaminergic mechanisms of alcohol and drug abuse Funded by NIDA, NIAAA and DOE # The role of dopamine and its receptors on alcohol, drug abuse and obesity using animal models (knockout mice, rats). -Developing gene therapy techniques for treatment of these addictions. -microPET imaging of the rodent brain treated with gene therapy -Correlating these findings with clinical studies on alcoholism, drug abuse and obesity)"