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 specific, 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 specificity, 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 effects of matricellular signaling on diverse cellular functions and processes. For example, we exploit peptide-crosslinked PEG hydrogels to encapsulate human mesenchymal stem cells (hMSCs) and study how matrix density, degradability, elasticity, and adhesivity influence 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.
Kristi S. Anseth earned her B.S. degree from Purdue University in 1992 and her Ph.D. degree from the University of Colorado in 1994. After completing post-doctoral research at MIT as an NIH fellow, she joined the Department of Chemical and Biological Engineering at the University of Colorado at Boulder as an Assistant Professor in 1996. Dr. Anseth is presently 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. Dr. Anseth is an elected member of the National Academy of Engineering (2009), the National Academy of Medicine (2009), the National Academy of Sciences (2013), and the National Academy of Inventors (2015). She is also a dedicated teacher, who has received four University awards related to her teaching, as well as the American Society for Engineering Education’s Curtis W. McGraw Award. Dr. 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 Biomacro-molecules, Progress in Materials Science, and Biotechnology & Bioengineering.