BioNanotechnology Seminar Series - Spring 2011

Iron-Mediated Lipid Peroxidation and Lipid Raft Disruption in Low-Dose
Silica-Induced Macrophage Cytokine Production

Dr. Valerie Leppert, University of California, Merced, School of Engineering

Tuesday, May 24, 2011
1000 MNTL, 12:00 - 1:00 PM

Abstract: Over the past two decades, an increasing number and variety of microscale and nanoscale materials have been developed for medical diagnostics and therapeutics, as well as for a multitude of technological and consumer applications. However, many questions still remain as to their toxicity, due to both the variety of materials properties that may lead to toxicity (e.g. phase, size, surface chemistry, contaminants, and agglomeration) and incomplete characterization of these properties for cellular and whole animal studies. A lack of understanding of toxicity mechanisms further complicates the effort to understand which materials properties are of concern and how they can be controlled to minimize toxicity. Here, we present results from our investigations of the pro-inflammatory effects of silica particles on alveolar macrophages. Of particular note in this work is the use of sub-lethal doses that approximate a more realistic exposure scenario compared to most studies published in the literature, and testing of a novel hypothesis for an iron-mediated mechanism for silica particle-induced pro-inflammatory effects. Specifically, we studied the role of particle size and iron, a common contaminant in natural and engineered micro/nanophases, in lipid peroxidation-dependent transcription of cytokines in THP-1 macrophages induced by well-characterized silica particles.


Shrink Induced Nanostructures and Microsystems for Biomedical Applications

Dr. Michelle Khine, University of California, Irvine, Department of Biomedical Engineering

Tuesday, May 10, 2011
1000 MNTL, 12:00 - 1:00 PM

Abstract: The challenge of micro- and nano-fabrication lies in the difficulties and costs           associated with patterning at such high resolution. Instead of relying on traditional fabrication techniques -- largely inherited from the semiconductor industry -- for    microfluidic applications, we have developed a radically different approach. We    pattern at the large scale, which is easy and inexpensive, and rely on the heat-induced relaxation of pre-stressed polymer sheets to achieve our desired structures. Using this approach, we have demonstrated that we can create fully functional and complete   microfluidic devices with integrated nanostructures within minutes. These devices can be created for only pennies per chip and without any dedicated costly equipment. This enables researchers to make custom micro- and nano-tools for a range of needs, from basic biological studies to tissue engineering applications to point of care diagnostics for the detection of infectious diseases.


Imaging Microvascular Blood Flow with MRI   |   View Presentation

Dr. Brad Sutton, Department of Bioengineering

Tuesday, April 26, 2011
1000 MNTL, 12:00 - 1:00 PM

Abstract: Blood flow in the brain is an important physiological quantity relating to vitality of brain tissue and performance of cognitive tasks. Current non-invasive methods to measure cerebral blood flow with magnetic resonance imaging (MRI) allow for the measurement of delivery of blood from feeding arteries and may be sensitive to disruptions in flow in pathways between where blood is tagged and where it is measured. Recently we have revived old techniques and developed new techniques for localized imaging of microvascular blood flow in the brain. In addition to flow quantification, our techniques allow for measurement of structural arrangement of microvasculature. In this talk, we will show how microvascular blood flow can be quantified in brain tissues using non-invasive methods of FENSI and diffusion weighted imaging.


Engineering Cellular Microenvironments for Biomedicine

Dr. Brendan Harley, Department of Chemical and Biomolecular Engineering

Tuesday, April 12, 2011
1000 MNTL, 12:00 - 1:00 PM

Abstract: The extracellular matrix (ECM) is a complex organization of structural proteins such as collagens and proteoglycans. Heterogeneous tissues with spatially and temporally modulated properties and their biomaterial mimics play an important role in organism physiology and regenerative medicine. With the understanding that the microstructure, mechanics, and composition of the ECM is dynamic and often spatially patterned or heterogeneous over the length-scale of traditional biomaterials, there has recently been significant effort aimed at moving away from static, monolithic biomaterials towards instructive biomaterials that provide specialized cell behavioral cues in spatially and temporally defined manners. We have been developing patterned, tunable biomaterial systems to explore the practical significance of how cell/matrix cues can be optimized to improve biomaterial regenerative potential and the mechanistic details of how individual (stem) cells sense, integrate, and respond to multiple microenvironmental signals. Here I will present the development of biomaterials for traditional regenerative medicine applications as well as stem cell fate engineering. We are developing collagen scaffolds and photolithography-based biomolecule patterning tools for the regenerative repair of orthopedic defects. We are also creating multi-gradient and combinatorial biomaterials for rigorous investigation of fundamental questions regarding niche-mediated regulation of hematopoietic stem cell (HSC) behavior. Here microfluidic tools aid our investigation of the role played by matrix elasticity, ligand presentation, and paracrine-mediated signaling on HSC fate.


Development of Anticancer Nanomedicine   |   View Presentation

Dr. Jianjun Cheng, Department of Materials Science and Engineering

Tuesday, March 29, 2011
1000 MNTL, 12:00 - 1:00 PM

Abstract: Nanoparticles are promising carriers for the delivery of chemotherapeutics for cancer therapy because they are able to carry large payload of therapeutic modalities, extravasate leaky tumor vasculatures, and mediate sus-tained drug release in tumor tissues. However, over the past several decades there has been only very limited clinical success of anticancer nanomedicine because of tremendous issues related to their formulation. We de-veloped various controlled chemistries and engineering processes to prepare anticancer nanomedicines with well-controlled physicochemical and biological properties. In one study, we developed the nanoconjugation technique, utilizing hydroxyl-containing therapeutic agents initiated lactide polymerization followed by nano-precipitation to develop polymeric nanoconjugates with defined drug loading, quantitative loading efficiency and controlled release profiles. We also developed drug-conjugate silica nanoparticles with precisely con-trolled particle sizes and demonstrated the size-dependent tumor tissue penetration. Preliminary studies on cancer targeting using aptamer-nanoparticle conjugates was also evaluated and demonstrated in vitro and vivo.


Cardiovascular Stem Cell Engineering for Regenerative Medicine

Dr. Kara McCloskey, University of California, Merced, School of Engineering

Tuesday, March 8, 2011
1000 MNTL, 12:00 - 1:00 PM (live via videoconference)

Abstract: Stem cells could potentially lead to a variety of clinically relevant cell-based therapies, and hold promise in providing cell sources for tissue engineering. Two obstacles associated with using embryonic stem cells (ESC) for regenerative medicine applications include a) isolating homogeneous populations of differentiated cells, and b) obtaining terminally differentiated cell populations that are fully functional and retain significant expansion potential. Our laboratory has investigated the differentiation of vascular endothelial cell (EC) and smooth muscle cells (SMC) from both mouse and human ESC. We have developed serum-free methods for isolation of homogeneous differentiated cell populations of endothelial cells and thoroughly characterized these cells for both surface and functional markers. We have also demonstrated the ability of our ESC-derived EC to readily assemble into neovessels in vitro, exhibiting increased angiogenesis compared with primary EC. More recently, these studies have been expanded to include cardiac differentiation and cardiac cell alignment for generating functional cardiac tissues.


Biomaterials for Angiogenesis Study

Hyunjoon Kong, Department of Chemical and Biomolecular Engineering

Tuesday, February 22, 2011
1000 MNTL, 12:00 - 1:00 PM

Abstract: Angiogenesis is one of key biological events involved in development, tissue regeneration, and various malig-nant diseases including cancer. Various growth factors, cytokines and cells are extensively being studied to un-derstand their roles in both therapeutic and pathologic angiogenesis. Successes in these studies greatly rely on the ability to tune the bioactivities of angiogenic factors and cells, but the required tools are still lacking. This seminar will present biomaterials developed to control the molecular and cell activities, and ultimately the quality of blood vessels (i.e., maturity, area density, etc). First, I will discuss a colloidal microgel system which enabled us to control the spatial distribution of angiogenic factors at implant sites. Second, I will show a cell-encapsulating hydrogel which can regulate cellular expression of angiogenic factors with matrix properties in-cluding mechanics and permeability.