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Tissue engineering

Shell-reinforced macroporous hydrogels for bone repair

Nature Reviews Materials volume 10, page 333 (2025)Cite this article

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The macroporous structure is formed by mixing polyethylene glycol (PEG) and dextran, which undergo aqueous phase separation into two immiscible phases: PEG forms the percolating (continuous) phase, whereas dextran forms droplets dispersed throughout. Upon the cross-linking of the PEG phase to create the hydrogel network, dextran serves as a soft template, and its subsequent removal creates interconnected macropores. Two PEG cross-linkers — one degradable and one non-degradable — are used to control the hydrogel’s degradation rate by varying their ratio. To reinforce the outer shell and provide mechanical stability, rigid protein fibres are also introduced, ultimately forming a stiff shell around each pore.

To prepare cell-encapsulated hydrogels, stem cells are added directly to the dextran phase before phase separation, resulting in their entrapment within the macropores. The surrounding stiff shell shields cells from sensing the bulk hydrogel stiffness, instead directing their response through local mechanical cues. This process, known as mechanotransduction, activates signalling pathways that guide stem cell fate based on mechanical input. Here, the localized stiffness mimics that of native bone tissue, promoting osteogenic differentiation.

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  1. Nature Reviews Materials http://www.nature.com/natrevmats/

    Charlotte Allard

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  1. Charlotte Allard
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Correspondence to Charlotte Allard.

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This text on an editorially selected paper was initially drafted using artificial intelligence, then revised and fact-checked by an editor to meet Nature Portfolio publication standards.

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Allard, C. Shell-reinforced macroporous hydrogels for bone repair. Nat Rev Mater 10, 333 (2025). https://doi.org/10.1038/s41578-025-00806-1

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  • DOI: https://doi.org/10.1038/s41578-025-00806-1

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