Cues from a cell’s microenvironment play a critical role in directing and maintaining cell fate in vivo. Misregulation within the extracellular space can cause cell death or other aberrant behaviors associated with developmental defects and diseases such as fibrosis and cancer. Thus, as one thinks about culturing cells for functional studies or delivery of cells into patients for therapeutic purposes, it is prudent to consider the surrounding microenvironment so that cells can be supported in a manner that stimulates desired biological functions and/or integration with native tissue. In this regard, multicomponent biomaterials and their physicochemical manipulation can serve as in vitro platforms to decipher some of the complexities in this dynamic signaling. This talk will focus on some of our recent efforts towards in situ hydrogel property manipulation with light, allowing intimate control of a cell’s microenvironment in both time and space [1]. In one approach, we engineer strategies to selectively release multiple growth factors at different time points from a single hydrogel formulation. BMP-2 and BMP-7 are tethered to gels through two distinctive photocleavable units, nitrobenzyl ether and coumarin methylester, to regulate their sequential release and study their influence on osteogenic differentiation of human mesenchymal stem cells [2]. In a second approach, spatial control of loading of multiple proteins is achieved by exploiting multiple, parallel photo-click chemistries. The approach preserves the activity of the protein and provides a complementary strategy to the photocleavage approach for loading and releasing hydrogels with proteins and subsequent spatiotemporal control of their presentation to cells. [1] N. Gandavaparu, M. Azagarsamy, K. Anseth, Adv Mater, 2014, 26, 2521; C. Yang, M. Tibbitt, L. Basta, K. Anseth,, Nat Mater, 2014 13, 645; D. McKinnon, T. Brown, K. Kyburz, E. Kiyotake, K. Anseth, Biomacromolecules, 2014, 5, 2808. [2] M. Azagarsamy, K. Anseth, Angewandte Chemie, 2013, 52, 13803.

Synthesis of dynamic stem cell niches using bioorthogonal photo-click chemistries

251st National Meeting (2016)

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