02/02/17 -9:45 AM to 11:00 AM
Etter Memorial Lecture: Professor Kristi Anseth
Margaret C. Etter Memorial Lecture in Materials Chemistry
"Hydrogels as synthetic ECM analogs through bio-click reactions"
Our group is interested in the development of biomaterials to serve as in vitro cell culture systems and decipher critical extracellular matrix (ECM) signals that are relevant in tissue development, regeneration, and disease. Specifically, we design synthetic ECM analogs that capture key features of the unique chemistry and physical properties of a cell’s niche—an environment that is not only tissue speci c, but can be strikingly heterogeneous and dynamic. Unique to our approach is the ability to create cell-laden matrices in three-dimensional space in which the matrix properties can be changed on demand—so-called 4D biology. Hydrogels functionalized with peptides, proteins and small molecules represent an important class of biomaterials for cell culture; however, 4D culture requires that cells be directly encapsulated during gel formation necessitating novel biorthogonal chemistries. Here, our group has focused on the development of bio-click materials to create tunable cell-laden matrices, using strain-promoted azide alkyne cycloaddition, photoinitiated thiol-ene polymerizations, and bio-orthogonal tetrazine-norbornene coupling through inverse electron demand Diels-Alder. These bio-click reactions not only proceed rapidly and with high speci city, but are bioorthogonal. This talk will illustrate how we leverage these chemistries to present bioactive peptides, signaling ligands, and small molecules at will, and employ them to study the e ects of matricellular signaling on diverse cellular functions and processes. For example, we exploit peptide-cross- linked PEG hydrogels to encapsulate human mesenchymal stem cells (hMSCs) and study how matrix density, degradability, elastic- ity, and adhesivity in uence migration in real time. These 3D culture systems are important when testing hypotheses related to cell migration, protease activity, and paracrine signaling; all of which depend strongly on the surrounding microenvironment and cannot be captured in 2D culture. Beyond simply observing cells, we also apply microrheological techniques to measure local gel degradation, and reporter molecules to detect local cell activity in situ (e.g., protease activity, apoptosis). Finally, results will demonstrate that these reactions are compatible with protein encapsulation and conjugation while maintaining bioactivity for cellular signaling.
Professor Anseth's research
Professor Anseth and her research group pioneer the development of biomaterials to serve as synthetic extracellular matrix (ECM) analogs that capture key features of the biochemical and biophysical aspects of a cell’s niche—an environment that is not only tissue specific, but can be strikingly heterogeneous and dynamic. Unique to her approach is the ability to create cell-laden matrices in three-dimensional space in which the matrix properties can be changed on demand—so-called 4D biology. Ultimately, Anseth and her group seek to understand how cells sense, store, and exchange information with the ECM and then use this knowledge to engineer biomaterial niches as cell delivery vehicles for tissue regeneration, in vitro models of disease, and physiologically-relevant models for drug discovery and screening. Her materials-first approach provides tools to perform unique cell biology experiments and address major hurdles in regenerative medicine.
Anseth's recent progress includes innovations in both photochemical and bio-click reactions to manipulate biomaterial properties in space and time, along with lithographic processes and confocal microscopy to perform these reactions in real time and in cell-laden matrices. She pursues application of these bioscaffolds to: (i) elucidate how specific extracellular signals influence stem cell differentiation, (ii) promote and mimic cell-cell interactions and to protect transplanted cells from the immune response via bioactive interfaces, and (iii) understand the fibroblast-to-myofibroblast transition in fibrosis, with an emphasis on the role of mechanotransduction
About Professor Anseth
Professor Kristi Anseth joined the Department of Chemical and Biological Engineering at the University of Colorado at Boulder as an assistant professor in 1996. Presently, she is a Howard Hughes Medical Institute Investigator as well as a Distinguished Professor and the Tisone Professor of Chemical and Biological Engineering at CU. Her research interests lie at the interface between biology and engineering where she designs new biomaterials for applications in drug delivery and regenerative medicine. She is an elected member of the National Academy of Engineering, the National Acad- emy of Medicine, the National Academy of Sciences, and the National Academy of Inventors. She has received four university awards related to her teaching, as well as the American Society for Engineering Education’s Curtis W. McGraw Award. Anseth is a Fellow of the American Association for the Advancement of Science, the American Institute for Medical and Biological Engineering, the Materials Research Society, the American Institute of Chemical Engineers, and the International Union for Biomaterial Science and Engineering. She is currently the President of the Materials Research Society and also serves as an editor for Biomacromolecules, Progress in Materials Science, and Biotechnology & Bioengineering.
Margaret C. Etter Memorial Lecture in Materials Chemistry
Margaret “Peggy” Cairns Etter was born on September 12, 1943. She died on June 10, 1992, from cancer. In 1974, she received her doctorate in chemistry from the University of Minnesota under the direction of Jack Gougoutas. She taught organic chemistry at Augsburg College in 1975-76, and worked at the 3M Company from 1976 to 1983. She returned to the University of Minnesota as a postdoctoral fellow with Robert Bryant in 1984 and, within a year, had secured an independent academic appointment. Peggy rose rapidly through the ranks and in 1990 was promoted to full professor. Peggy’s outstanding characteristics as a scientist were her infectious enthusiasm, uncompromising scientific standards, and creativity. Her research group made major contributions in the applications of solid-state nuclear magnetic resonance spectroscopy, the design and properties of organic non-linear optical materials, and most significantly, in the understanding and utilization of hydrogen-bonding interactions in crystals. This was reflected in nearly 80 research papers and in several landmark review articles in prestigious journals. Outside recognition in the form of fellowships from the Sloan and Bush Foundations and an Iota Sigma Pi Award for Excellence in Chemistry represent incomplete re ections of the impact of this work. One of her extramural “side projects” was to found a company called “Rochelle Crystal Corporation,” for which Peggy was named Saint Paul Businessperson of the Year in 1986.