Multivalent Host–Guest Hydrogels as Fatigue-Resistant 3D Matrix for Excessive Mechanical Stimulation of Encapsulated Cells

Fatigue resistance of hydrogels is critical to their applications in load-bearing sites of soft tissues that are usually subjected to continuous loadings, such as joint cartilage. However, hydrogels usually swell under physiological conditions and exhibit inevitable fatigue during excessive mechanical loadings. Here we show that hydrogels cross-linked by multivalent host–guest interactions can effectively dissipate a large fraction of the loading energy (>50%) under excessive compressions (over 80% strain, 1000 cycles) despite their high water contents (95%) under physiological conditions. No fatigue is observed in such highly swollen hydrogels during continuous cyclic compressions. We demonstrate that such hydrogels can be used as 3D cell carriers for excessive mechanical stimulation of the encapsulated stem cells, making them promising soft biomaterials for tissue engineering.