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

Authors

• Jonathan M. Zuidema, University of KentuckyFollow
• Alessandro Ajo, Istituto di Ricerche Farmacologiche Mario Negri “IRCCS”
• Marco Carofiglio, Istituto di Ricerche Farmacologiche Mario Negri “IRCCS”
• Luisa De Cola, Istituto di Ricerche Farmacologiche Mario Negri “IRCCS”Follow

Abstract

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.

Document Type

Article

Publication Date

2026

Notes/Citation Information

© 2025 The Authors. Published by American Chemical Society

Digital Object Identifier (DOI)

https://doi.org/10.1021/acsomega.5c07004

Funding Information

This project received funding through the European Union’s Horizon 2021 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 101067770 (“PACMAN”). J.M.Z. undertook this work as a Marie Skłodowska-Curie fellow. J.M.Z. is a Lighthouse Beacon Foundation Scholar. L.D.C. thanks Next Gen EU and MUR, Project PNRR M4C2, “Mano-HCC”, PE_00000019, HEAL ITALIA, CUP E93C22001860006 for support.

Repository Citation

Zuidema, Jonathan M.; Ajo, Alessandro; Carofiglio, Marco; and De Cola, Luisa, "Cross-Linking PEG Microgels with Mesoporous Organosilica Nanoparticles to Engineer Microporous Annealed Particle Scaffold Properties" (2026). Mechanical Engineering Faculty Publications. 99.
https://uknowledge.uky.edu/me_facpub/99