Category: Seminars

Tissue Engineered Models for Fundamental Study and Treatment of Heart Valve

Wednesday, January 19
211 Chemical Sciences & Engineering Building
2:00 pm

Presenter: Zannatul Ferdous, Ph.D., Parker H. Petit Institute of Bioengineering and Bioscience Georgia Institute of Technology

Abstract: My research uses unique model systems to study mechanisms and causes of cardiovascular diseases, particularly pathologies of heart valves. Valve diseases and defects are major causes of mortality in the elderly population and children in the US. Since altered expression of decorin has been observed in diseased heart valves, for my graduate research, the roles of proteoglycan decorin on extracellular matrix remodeling and tissue mechanics were investigated. Using tissueengineered collagen gels, we demonstrated that decorin-mediated matrix remodeling was heavily modulated by decorin-transforming growth factor beta (TGF-β) interaction. In addition, cyclic strain promoted compensatory behavior in collagen gels containing decorin-deficient cells, suggesting the influence of tissue mechanics on cellular function. We also showed the utility of a proper chemical and mechanical environment for studying  ex vivo tissue systems. For my postdoctoral research, the contributions of mechanical forces to the initiation and progression of vascular and valvular calcification are being studied using cells isolated from non-sclerotic human tissues. We have observed that expression of osteogenic and matrix remodeling markers are dependent on both cell source (vascular versus valvular) and mechanical strain. In addition, calcification is observed to be modulated by the magnitude of strain (physiological versus pathological) applied to either cell types. We anticipate that the tissue-engineered model would help determine biomarkers for early detection and prevention of valve calcification. Additionally, the roles of microRNAs (miRNAs) in valvular diseases are also being investigated using RNAs isolated from endothelial cells in freshly isolated porcine valves. We hope that this research would lead to the discovery of important miRNAs and their roles in aortic valve biology and diseases. Continued research would therefore improve our knowledge of the complex heart valve environment and help determine treatment options for the large population of elderly and children in need for valve replacement.

Recreate Biomimetic Microenvironment for Regenerative Medicine Tissue-engineering of Scaffold-free Small-diameter Blood Vessel

Tuesday, January 11
U113 M&M Building
2:00 pm

Presenter: Feng Zhao, Ph.D., Department of Biomedical Engineering, Duke University

Abstract: The recreation of a natural microenvironment is  of significant importance to realize the regeneration potential of cells for engineering functional tissues.  My research aims to replicate the in vivo cell-cell and cell-environment interactions by manipulating biomaterials, oxygen tension, and hydrodynamic culture conditions in a precisely controlled manner.  The current study focuses on tissue-engineering of scaffold-free small-diameter blood vessel using human mesenchymal stem cells (hMSCs) based on their unique antithrombogenic property, immunomodulatory ability, and pluripotency for differentiation into vascular phenotypes. The fulfillment of the therapeutic application of tissue-engineered blood vessel (TEBV) from hMSCs requires the cells to maintain high viability, organization, and stemness.  By culturing hMSCs under the combined stimulation of nanotopographical cue and low oxygen tension, an extensively aligned cell sheet was fabricated with well-preserved stemness and viability. The physiologically low O2 (2%) tension significantly improved the confluency and extracellular matrix proteins secretion of the cells, which facilitated the process of cell sheet harvesting.  The fabrication of a completely biological tubular structure was achieved by wrapping the aligned hMSC  sheets around a temporary supporting mandrel. Maturation of the cellular construct in the rotating wall bioreactor reinforced its mechanical stability and allowed its development into an implantable  small-diameter TEBV.  The preliminary animal study in a rat femoral artery model demonstrated the remodeling of the vascular graft as well as the infiltration of endothelial cells into the hMSC-based TEBV.

Engineering Microenvironment for Neurogenesis

Friday, December 3
U113 M&M Building
11:00 am

Presenter: Li Yao, Ph.D., National Center for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

Abstract: Advances in neuroscience over the past two decades begin to offer hope for patients with injury in nervous system. Since the demonstration in 1980 that central  nervous system axons have the capacity to regenerate within peripheral nervous system graft, much has been accomplished toward understanding factors that contribute to a physiologically permissive environment. Axonal regeneration after injury or disease is the major challenge in both peripheral and central nervous system. Neural engineering is a promising approach for axonal regeneration by preventing inhibitory factors and enhancing guided axonal growth. In peripheral nerve regeneration, neural conduits have been investigated to bridge nerve defects. In our recent study, the advance in the design of engineered scaffolds that mimic peripheral nerve multiple basal lamina have improved guided axonal regeneration in vivo. Despite recent advances, the limited demonstration of functional improvement in in vivo models of spinal cord injury has prevented advancement of regenerative therapy to clinical use. This may be due in large part to the multifaceted nature of spinal cord injuries, which presents a major challenge to therapeutic development. In order for viable treatment strategies to be realized clinically, it is likely that combinations of current therapeutic approaches must be used. We are developing a functionalised graft that targets injury mechanisms at the molecular, cellular and tissue levels of spinal cord  injury. Biodegradable polymers can simultaneously provide structural guidance at a cellular level and a reservoir  for sustained gene delivery. This integrative approach suggests a possible treatment strategy and may serve as an in vivo model for studying optimisation of various combinations of treatments.  Effectively directed neuron migration is critical for development and repair in the central nervous system. Endogenous electrical signals are present in many developing systems and crucial cellular behaviours such as neuronal cell division, cell migration and cell differentiation are all under the influence of such endogenous electrical cues. Pre-clinical in vivo studies have used electric fields to attempt to enhance re-growth of damaged spinal cord axons with some success. We recently demonstrated that small electric fields not only guide axonal growth, but also can direct the earlier events of neuronal migration and neuronal cell division. This raises the possibility that applied or endogenous electric fields, perhaps in combination, may direct transplanted neural stem cells, or regenerating neurons, to the desired site after brain injury or neuron degeneration. The high complexity of both structure and function of the central nervous system however, poses significant challenges to techniques for applying electric fields to promote neurogenesis. The evolution of functional biomaterials and nanotechnology may provide promising solutions for the application of electric fields in guiding neuron migration in neurogenesis within the central nervous system.

First in vivo Measurement of Differential Motion in the Guinea Cochlea

Monday, October 4
211 Chemical Sciences Building
3:00 pm

Presenter: Niloy Choudhury, Ph.D., Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon

Abstract: Auditory response in mammals depends upon an amplifying mechanism which hypothetically uses forces from outer hair cell (OHC) motility to enhance sound-induced vibration of the organ of Corti in the cochlea. Differential motion among key structures in this organ and proper timing of OHC force generation are essential to this hypothesis.  An optical coherence tomography (OCT) system was designed and built to image the microstructures and measure mechanical vibrations at different cellular structures in the guinea pig cochlea.  The traditional OCT system was modified to  allow measure of nanometer scale vibration motion.  The new scheme  allows quantitative values for phase and amplitude vibration in the presence of bulk animal motion.  The engineering of the system as well as the first ever  in vivo measurements of differential motion of two functionally important structures in the organ of Corti, the basilar membrane and reticular lamina, will be presented.  Results show that the reticular lamina vibrates at a greater magnitude than the basilar membrane and has a significant phase lead.  Similar phase relation between OHC receptor potentials and basilar membrane motion were observed. These results demonstrate that a powerful enhancement of vibration occurs at the apical surface of sensory hair cells and that  OHC force generation is optimally timed for counteracting viscosity-related energy loss.

RNA Splicing and Polyadenylation Control in Retroviruses: Implications for Cellular Control

September 3, 2010

U113 M&M

2:00 – 3:00 pm

Presenter: Dr. Mark McNally, Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee

Abstract: Characterizing unique virus-host interactions is key to understanding pathogenesis and developing therapeutics to block the virus life cycle. Because of their intimate associations with host cells, viruses have also been exploited as tools for studying many basic cellular processes, including RNA processing. For retroviruses, control of splicing and polyadenylation is an important aspect of the replication cycle. Splicing of retroviral primary transcripts must be controlled since high levels of unspliced RNA are needed as mRNA, and for incorporation as genomes into progeny virions. Polyadenylation control is important because failure to use the viral polyadenylation site results in read-through transcripts that extend into downstream genomic sequences; this is the basis for oncogenic transformation and the ability of retroviruses to acquire host cell sequences through oncogene capture. We are studying viral cis elements and host trans-acting factors required for proper RNA processing and replication of Rous sarcoma virus (RSV), not only to further an understanding of virus replication but to provide insights into host cell RNA processing regulation. Our work focuses in part on a novel RNA processing control element, the negative regulator of splicing (NRS), that contributes to the accumulation of genome-length RNA by acting as a pseudo 5’ss to repress splicing. We continue to study a host factor, hnRNP H, that is required for high-efficiency binding of U11 snRNP (a splicing factor in the ‘minor’ splicing pathway that binds to 5′ splice sites) to the NRS, with an eye towards deeper understanding of its role in alternative splicing of cellular genes. Interestingly, the NRS is also required for proper polyadenylation of viral RNAs, and we have made the novel finding that a class of splicing factors (SR proteins) mediates stimulation of polyadenylation by the NRS in a position-dependent manner; this observation suggests that some cellular mRNAs might use a similar mechanism of polyadenylation control. Thus, the RSV system has provided a powerful tool to dissect novel cellular mechanisms of RNA processing regulation.

Developing artificial cells for therapeutic applications and refining bone marrow stimulation techniques for cartilage repair

Department of Biomedical Engineering Seminar: April 5: Dr. Hongmei Chen, Department of Chemical Engineering and Institute of Biomedical Engineering, Ecole Polytechnique of Montreal, Canada, titled, “Developing artificial cells for therapeutic applications and refining bone marrow stimulation techniques for cartilage repair,” at 3 p.m., in Fisher 129

Biologically Inspired Tissue-Engineered Bone and Cartilage Substitutes: A Next Generation Treatment for Musculoskeletal Injuries and Diseases

Wednesday, February 24
G06 Rekhi Hall
3:00 pm

Presenter: Lijie Zhang, PhD, Harvard Medical School, Brigham and Women Hospital, Department ofMedicineHarvard-MIT Division of Health Sciences and Technology (HST)

Abstract: Various bone and articular cartilage defects, caused by trauma, disease or age-related degeneration, representa crucial clinical problem all over the world. However, traditional implant treatments may cause manycomplications after surgeries, leading to intense patient pain. Thus, our research aims to create biologicallyinspired tissue-engineered bone, cartilage and osteochondral substitutes via state-of-the-art nanotechnologyand biotechnology for replacing damaged or diseased musculoskeletal tissues and recovering theirfunctionality.For this purpose, we have designed a series of nanostructured scaffolds with excellent cytocompatibility andmechanical properties based on biomimetic nanoceramic particles, rosette nanotubes (a novel biologicallyinspired nanotube obtained through the self-assembly of DNA base pairs in water), collagen and hydrogels.Different cell types including osteoblast (bone forming cell), endothelial cell, mesenchymal stem cell andfibroblast responses towards these nanocomposites were investigated. Our results demonstrated that thesebiomimetic nanocomposites with controllable surface chemistry can significantly enhance bone cellfunctions and osteogenic differentiation of mesenchymal stem cells, thus making them promising for furtherstudy in bone tissue engineering and orthopedic applications. Furthermore, I will also introduce our work incartilage tissue engineering. Through a novel self-assembling tissue engineering method, a cartilageconstruct was grown from chondrocytes and the mechanical, optical properties and extracellular matrixdistribution of these constructs were measured over times. In summary, the results of our study indicate theimportance of tissue-engineered bone and cartilage substitutes for improving current therapies ofmusculoskeletal disorders and diseases.

When Nano Meets Bio!

Monday, January 25
218 EERC
3:00 pm

Presenter: Kyung A. Kang, PhD, Department of Chemical Engineering, Professor and Graduate Program Director, University of Louisville

Abstract: Nano-sized particles have properties that are highly beneficial for biomedical applications.  Liposome and some biopolymeric nanoparticles have been already used for drug delivery.  Our group has been interested in developing metal nanoparticles for diagnosing and treating diseases.  A few examples of these nano-entities are listed below.

Optical Contrast Agent for Molecular Sensing. Fluorophores have been used as a signal mediator in biosensing and imaging for a long time.  Gold nanoparticles (GNP) possess high-density surface plasmon polarion fields that can be effectively used to enhance the sensitivity of bio- sensing and imaging.  We have been developing a highly specific, molecular beacon-like optical contrast agent for accurate  cancer detection/diagnosis utilizing the GNP’s ability of fluorescence quenching and enhancement ability.

Nanoparticle Mediated Hyperthermia.  An alternating electromagnetic (AEM) field at an appropriate frequency can heat nano-sized magnetic particles (MNPs) without heating surrounding tissue.  When iron oxide MNPs are used for cancer treatment (hyperthermia) they can guide the heat generated  by the non-invasively applied AEM field specifically to the tumor, minimizing normal tissue damage.  We have studied and designed novel AEM probe configurations for more user-friendly AEM energy application to the human body.

Multi-functional Nanoparticles.  Several metal nanoparticles also provide good contrast for imaging, e.g., iron oxide particles are a good MRI contrast agent and gold particles enhance the contrast of X-ray/CT.  By combining these beneficial features, multi-functional nano-entities can  be developed, enabling seamless disease diagnoses and treatment.