The nano- to macro-scale physical and chemical properties of the environment that surrounds a cell play an important role in cell function and fate. For example, driven by transient bidirectional crosstalk between cells and the extracellular matrix (ECM), cell activation and tissue remodeling are complex processes that often involve the presentation of multiple cues over multiple time and size scales. Biomaterials, particularly synthetic hydrogels, are useful tools for probing how microenvironment cues regulate cell behavior toward directing cellular functions in the treatment of disease and regeneration of tissue. Further, these materials can be utilized to deliver therapeutics, from proteins to cells, to regulate these processes in vivo. Molecular engineering of hydrogel-based materials enables controlled presentation of selected cues at the appropriate time and place within the cell microenvironment. This talk will focus on simple strategies to impart highly-regulated property control by synthesizing monomers with homogenous or hierarchical nanostructures that allow formation of hydrogels in the presence of cells and proteins and subsequently triggered modification (e.g., light, enzymes, temperature, or reducing conditions) to tune the physical or chemical properties of the network. In particular, we will highlight recent results in the construction of soft, well-defined synthetic matrices with controlled nano- and micro-structure, mechanical properties, and biochemical content, achieved utilizing a combination of assembling and orthogonal covalent chemistries, for two- and three-dimensional culture studies, such as the activation of wound-healing cells or cancer cells with relevance for improved culture models and regenerative medicine. Additionally, we will highlight efforts in the design and in vivo deployment of responsive hydrogel-based depots for local, controlled release of therapeutics to modulate cell microenvironments in the body.
April M. Kloxin, Ph.D., is Centennial Development Professor of Chemical and Biomolecular Engineering, an Associate Professor in Chemical and Biomolecular Engineering and Materials Science and Engineering at the University of Delaware (UD), and a member of the Breast Cancer Research Program at the Helen F. Graham Cancer Center and Research Institute in the Christiana Care Health System. She obtained her B.S. and M.S. in Chemical Engineering from North Carolina State University and Ph.D. in Chemical Engineering from the University of Colorado, Boulder, as a NASA Graduate Student Research Program Fellow, and trained as a Howard Hughes Medical Institute Postdoctoral Research Associate at the University of Colorado, Boulder. Her multi-disciplinary group creates unique materials with multiscale property control and applies them in conjunction with other innovative molecular tools for addressing outstanding problems in human health, with a focus on understanding dynamic cell-microenvironment interactions in wound healing, fibrosis, and cancer. She is a recipient of the 2019 Biomaterials Science Lectureship, 2018 ACS PMSE Arthur K. Doolittle Award, a NIH Director’s New Innovator Award, a Susan G. Komen Foundation Career Catalyst Research award, a NSF CAREER award, and a Pew Scholars in Biomedical Sciences award.