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bioRxiv · 10.1101/2025.01.28.635095

Interparticle Crosslinked Ion-responsive Microgels for 3D and 4D (Bio)printing Applications

Pal, V.·Gupta, D.·Liu, S.·Namli, I.·Rizvi, S. H. A.·Yilmaz, Y. O.·Haugh, L.·Gerhard, E. M.·Ozbolat, I. T.
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Abstract

AbstractMicrogels offer unique advantages over bulk hydrogels due to their improved diffusion limits for oxygen and nutrients. Particularly, stimuli-responsive microgels with inherently bioactive and self-supporting properties emerge as highly promising biomaterials. This study unveils the development of interparticle-crosslinked, self-supporting, ion-responsive microgels tailored for 3D and 4D (bio)printing applications. A novel strategy was proposed to develop microgels that enabled interparticle crosslinking, eliminating the need for filler hydrogels and preserving essential microscale void spaces to support cell migration and vascularization. Additionally, these microgels possessed unique, ion-responsive shrinking behavior primarily by the Hofmeister effect, reversible upon the removal of the stimulus. Two types of microgels, spherical ({micro}S) and random-shaped ({micro}R), were fabricated, with {micro}R exhibiting superior mechanical properties and higher packing density. Fabricated microgel-based constructs supported angiogenesis with tunable vessel size based on interstitial void spaces while demonstrating excellent shear-thinning and self-healing properties and high print fidelity. Various bioprinting techniques were employed and validated using these microgels, including extrusion-based, embedded, intraembedded, and aspiration-assisted bioprinting, facilitating the biofabrication of scalable constructs. Multi-material 4D printing was achieved by combining ion-responsive microgels with non-responsive microgels, enabling programmable shape transformations upon exposure to ionic solutions. Utilizing 4D printing, complex, dynamic structures were generated such as coiling filaments, grippers, and folding sheets, providing a foundation for the development of advanced tissue models and devices for regenerative medicine and soft robotics, respectively.

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Pal, V., Gupta, D., Liu, S., Namli, I., Rizvi, S. H. A., Yilmaz, Y. O., Haugh, L., Gerhard, E. M., Ozbolat, I. T.. 2025-02-02. Interparticle Crosslinked Ion-responsive Microgels for 3D and 4D (Bio)printing Applications. https://doi.org/10.1101/2025.01.28.635095

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