Cross-Linking PEG Microgels with Mesoporous Organosilica Nanoparticles to Engineer Microporous Annealed Particle Scaffold Properties

Microporous annealed particle (MAP) scaffolds composed of cross-linked microgels are emerging as important biomaterials due to their modular design, high porosity, and large surface area, which allow for highly tailored properties, cellular infiltration, nutrient and waste exchange, and improved drug release characteristics. To further expand on these technologies and enhance their modular design, thiolated mesoporous organosilica nanoparticles (ssMSN-SH), which degrade in response to glutathione, were first cross-linked inside of 4-arm poly-(ethylene glycol) maleimide microgels. The microgel size, rheological properties, and payload release characteristics were determined. Hierarchical MAP scaffolds were then created by cross-linking 4-arm poly-(ethylene glycol) maleimide microgels with ssMSN-SH. Surface attachment and cross-linking of microgels using ssMSN-SH were confirmed with scanning electron microscopy and confocal imaging; rheological properties were characterized; porosity was analyzed; glutathione-induced degradation of MAP scaffolds was determined; and the depth of viable NIH/3T3 fibroblasts into MAP scaffolds was visualized using confocal microscopy. ssMSN-SH cross-linked microgels form MAP scaffolds with an increase in the storage modulus, maintain their porosity while decreasing the interparticle distance, degrade in response to glutathione, and increase the depth of viable NIH/3T3 fibroblasts into scaffolds when compared with bulk PEG hydrogels.