Fibrotic aortic valve stenosis (FAVS) is a heart disease that causes thickening and hardening of the valve leaflets, leading to heart failure. Members of this small group work to better understand disease at the cellular level, striving to elucidate preventative treatments and therapeutics. To accomplish this we use valvular interstitial cells (VICs) and photoresponsive hydrogels to study the transition from a quiescent fibroblast state to the activated myofibroblast phenotype. These studies reveal insights for maintaining valve function and treating chronic heart injury.
Innovation in materials development and characterization continues to be foundational in the Anseth group. By implementing cytocompatible "click" reactions for hydrogel crosslinking in concert with orthogonal photo-chemistries we have shown that it is possible to sequentially introduce and remove biochemical and biophysical signals with precise spatiotemporal control. While we now have a number of tools for engineering photoresponsive hydrogels, this small group works to expand these strategies by exploring alternative chemistries and materials platforms for cell culture.
Tissue homeostasis is maintained by a complex interplay between cells and their surrounding extracellular matrix (ECM). A milieu of chemical signals provide cues directing development, wound healing and disease progression. Likewise, the physical environment, such as stiffness and topography, can have a dramatic impact on cellular fate. The goal of this small group is to engineer material systems to better understand how cells receive biochemical and mechanical information from their microenvironment and exploit this knowledge to design better strategies for directing cell fate and regulating cell behavior for tissue regeneration.
Using microfabrication techniques such as soft lithography, microfluidics, and functional microparticle synthesis, members of this small group dynamically control the highly complex niches of various cellular microenvironments. Specifically, our focus is to develop microscale biosensors and microdynamically controlled extracellular environments. This helps to identify how key regulatory factors interact synergistically in native three-dimensional cellular environments. In doing so, we hope to apply this knowledge toward better understanding the fundamental aspects of cellular behavior to help guide the development of therapeutic treatments.
Intestinal organoids are self-organized, stem cell-derived, tissue constructs that recapitulate the structure and function of the intestinal epithelium in vitro. Organoids have gained popularity recently as models of intestinal development and disease progression, or as sources of tissue to conduct drug screens. The use of the heterogeneous and ill-defined 3D cell culture platform Matrigel has facilitated organoid culture with impressive versatility, but is not without limitations. In particular, culture in Matrigel results in highly variable organoids that are difficult to control in terms of size, shape, and cellular composition. Instead, members of this small group use novel synthetic hydrogel chemistries to study intestinal organoid development in more controlled environments. The use of phototunable and covalent adaptable hydrogels enables precise spatiotemporal control over the presentation of biophysical and biochemical cues, in order to gain a deeper understanding of the factors that influence organoid growth and development.