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Hydrogels that can reproduce the dynamic mechanical cues of native extracellular matrix are powerful tools for tissue engineering. Although it is increasingly recognized that stress relaxation and plasticity, among other cues, regulate cell-matrix interactions, the effects of these properties on mesenchymal stromal cells (MSCs) for cartilage formation, over a wide range of relaxation time scales, and in the absence of confounding biochemical cues, have not been clearly defined. This study reports an adaptable sliding hydrogel (ASG) as a novel cell niche for MSCs. By integrating reversible ketone cross-linking into a sliding hydrogel based on polyethylene glycol (PEG), ASG achieves multiple adjustable stress relaxation and plasticity, which are distinct from other dynamic hydrogels used for MSC cartilage formation. Notably, the enhancement of stress relaxation and plasticity in ASG promotes rapid and robust cartilage formation by human MSCs, supporting their long-term survival ability. Mechanistically, ASG promotes local matrix remodeling, enabling MSCs to form "cellular pocket" in three dimensions, associated with enhanced deposition and reorganization of the native extracellular matrix, integrin signal transduction, and nuclear dynamics. Overall, the ASG platform provides a tunable synthetic microenvironment, facilitating the exploration of the relationship between dynamic mechanical cues and stem cell fate, and offering a reference for the design of next-generation materials in the field of tissue engineering.
This study was published in Bioactive Materials under the title "Adaptable sliding hydrogels enable pericellular pocket formation while enhancing MSC chondrogenesis and survival in 3D".
Reference: DOI: 10.1016/j.bioactmat.2026.03.014
