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Microporous annealed particle (MAP) scaffolds are generated from assembled hydrogel microparticles (HMPs). We previously demonstrated that MAP scaffolds are porous, biocompatible, and recruit neural progenitor cells (NPCs) to the stroke cavity after injection into the stroke core. Here, our goal is to study NPC fate inside MAP scaffolds in vitro. To create plain HMPs that can later be converted to contain different types of bioactivities, we utilized the inverse electron-demand Deiels-Alder reaction between tetrazine and norbornene, which allowed us to post modify plain HMPs stoichiometrically. As a result of adhesive peptide attachment, NPC spreading led to contractile force generation which can be recorded by tracking HMP displacement. Alternatively, non-adhesive peptide integration results in neurosphere formation that grew within the void subunits of MAP. Although the formed neurospheres did not impose contractile force on the scaffolds, they were seen to continuously transverse the scaffolds. We concluded that MAP hydrogels can be engineered to either promote neurogenesis or enhance stemness depending on the chosen post-modifications, which can be key in modulating their phenotypes in various applications in vivo.

Wilson, KL; Pérez, SCL; Naffa, MM; Kelly, SH; Segura, T