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

Abstract

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.

Conformational manipulation of scale-up prepared single-chain polymeric nanogels for multiscale regulation of cells

“…Bulk biological tissues, such as muscles, possess considerable dynamic mechanical properties, including energy dissipation through force-induced temporal rupture of secondary structures 29–31 . The incorporation of elastomeric proteins or dynamic crosslinking structures has been shown to produce hydrogels with comparable energy-dissipating capacities mimicking muscles 32,33 . Developing a simple strategy to fabricate hydrogels with conformationally dynamic substructure, which allows precise tuning of the dynamic mechanical properties of the bulk material from a molecularly tailored approach, is highly desirable 32 .…”

Advanced Bottom‐Up Engineering of Living Architectures

“…The ability of such hydrogels to withstand high deformations has seldom been studied. To this end, researchers have explored acrylated‐β‐cyclodextrin and adamantane‐hyaluronic acid as macro‐crosslinkers of ductile polymers prepared through the polymerization of N , N ‐dimethylacrylamide monomers . This novel strategy yielded highly swollen cell‐laden hydrogels with outstanding resistance to fatigue, i.e., up to 80% compressive deformation for over 1000 cycles.…”

Low‐intensity pulsed ultrasound protects subchondral bone in rabbit temporomandibular joint osteoarthritis by suppressing TGF‐β1/Smad3 pathway

“…Nonsurgical techniques are the most commonly used treatments for TMJOA and include medications, physical therapies, and occlusal splints 4,5 . Recent studies demonstrated that the supramolecular hydrogels fabricated by cross‐linked, through multivalent host‐guest interactions, are applied to the treatment of OA due to their excellent mechanical robustness 6,7 . Although OA is considered a major disease resulting in cartilage degeneration, the role of subchondral bone in the pathogenesis of OA has attracted increasing attention in recent years 8 .…”

“…supramolecular hydrogels fabricated by cross-linked, through multivalent host-guest interactions, are applied to the treatment of OA due to their excellent mechanical robustness. 6,7 Although OA is considered a major disease resulting in cartilage degeneration, the role of subchondral bone in the pathogenesis of OA has attracted increasing attention in recent years. 8 Studies have demonstrated that significant subchondral bone changes occur following cartilage degradation in the condyle of TMJOA.…”