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bioRxiv · 10.1101/2025.03.26.645296

Biocompatible Composite Hydrogel with On-Demand Swelling-Shrinking Properties for 4D Bioprinting

Jensen, P. J.·Graham, J. P.·Busch, T. K.·Fitz, O. R.·Jayanadh, S.·Pashuck, E. T.·Gonzalez-Fernandez, T.
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Abstract

Hydrogels with tunable swelling and shrinking properties are of great interest in biomedical applications, particularly in wound healing, tissue regeneration, and drug delivery. Traditional hydrogels often fail to achieve high swelling without mechanical failure. In contrast, high-swelling hydrogels can absorb large amounts of liquid, expanding their volume by 10-1000 times, due to low crosslink density and the presence of hydrophilic groups. Additionally, some high-swelling hydrogels can also shrink in response to external stimuli, making them promising for applications like on-demand drug delivery and biosensors. An emerging application of high-swelling hydrogels is four-dimensional (4D) printing, where controlled swelling induces structural transformations in a 3D printed construct. However, current hydrogel systems show limited swelling capacity, restricting their ability to undergo significant shape changes. To address these limitations, we developed a high-swelling composite hydrogel, termed SwellMA, by combining gelatin methacryloyl (GelMA) and sodium polyacrylate (SPA). SwellMA exhibits a swelling capacity over 500% of its original area and can increase its original water weight by 100-fold, outperforming existing materials in 4D bioprinting. Furthermore, SwellMA constructs can cyclically swell and shrink on-demand upon changing the ionic strength of the aqueous solution. Additionally, SwellMA demonstrates superior cytocompatibility and cell culture properties than SPA, along with excellent 3D printing fidelity. These findings demonstrate SwellMAs potential for advanced 4D printing and a broad range of biomedical applications requiring precise and dynamic control over hydrogel swelling and shrinking.

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Jensen, P. J., Graham, J. P., Busch, T. K., Fitz, O. R., Jayanadh, S., Pashuck, E. T., Gonzalez-Fernandez, T.. 2025-03-29. Biocompatible Composite Hydrogel with On-Demand Swelling-Shrinking Properties for 4D Bioprinting. https://doi.org/10.1101/2025.03.26.645296

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