Gelatin-based thiol/disulfide degradable hydrogels to encapsulate cells

Statement of Purpose: A current and critical challenge in medicine and biology is understanding and replicating the array of cues that are responsible for controlling stem cell behavior. A major bottleneck is that it remains unclear how synergies and hierarchies between multiple niche signals affect the heterogeneity of stem cell response. Synthetic niches consisting of three-dimensional (3D) biomaterials have the potential to provide structural and molecular cues to guide and trigger a desired stem cell behavior. Thus, it is paramount to develop functional synthetic niches and technologies that allow the temporal tracking of niche remodeling and stem cell fate heterogeneity. Here, we report a gelatin-based hydrogel, adapting maleimide-thiol crosslinking chemistries from a PEG-based system¹ to generate libraries of miniaturized synthetic niches surrounding stem cells with defined cellular, structural, and biomolecular signals via a droplet microfluidic technique. This will enable the incorporation of instructive biomaterial networks within the individual droplets to make tractable a wide range of questions regarding how niche signals shape hematopoietic cell identity. Extensions of this effort will bring new precision to the design of synthetic stem cell niches to address a wider variety of traumatic injuries and degenerative diseases.