Invited: Bioinspired Hydrogels That Regulate Growth Factor Signaling

Control over the soluble signals that cells encounter in their local environment is a common theme in natural tissue formation, and also an emerging theme in functional tissue engineering strategies. This concept is particularly important in stem cell-based applications, in which local soluble signals can dictate cell fate decisions. Nature often achieves intricate control over local soluble signaling via specific, non-covalent interactions. Inspired by these natural interactions, we are interested in creating biomaterials that actively regulate soluble signaling. For example, our recent studies show that biomaterials can be designed to bind specific growth factor signaling components, including growth factors, growth factor receptors, and proteoglycans. We have used this approach to up- or down-regulate growth factor signaling in vitro and in vivo. One example uses soluble proteoglycan sequestering as a broad mechanism to regulate human mesenchymal stem cell proliferation and osteogenic differentiation in standard cell culture conditions. Another example explores the utility of injectable, growth factor-sequestering hydrogels in tissue engineering applications. In summary, our recent studies show that tailored non-covalent interactions between growth factors and biomaterials may provide an adaptable mechanism to control growth factor signaling and, in turn, stem cell behavior and new tissue formation.