Supramolecular hydrogels cross-linked by preassembled host–guest PEG cross-linkers resist excessive, ultrafast, and non-resting cyclic compression

Poly(ethylene glycol) (PEG)-based hydrogels are promising materials for biomedical applications because of their excellent hydrophilicity and biocompatibility. However, conventional chemically cross-linked PEG hydrogels are brittle under mechanical loading. The mechanical resilience and rapid recovery abilities of hydrogel implants are critical in load-bearing tissues, such as articular cartilage, which are routinely subjected to cyclic loadings of high magnitude and frequency. Here, we report the fabrication of novel supramolecular PEG hydrogels by polymerizing N,N-dimethylacrylamide with supramolecular cross-linkers self-assembled from adamantane-grafted PEG and mono-acrylated β-cyclodextrin. The resultant PEG–ADA supramolecular hydrogels exhibit substantial deformability, excellent capacity to dissipate massive amounts of loading energy, and have a rapid, full recovery during excessive, ultrafast, and non-resting cyclic compression. Furthermore, the energy dissipation capacity of the PEG–ADA (adamantane-grafted Poly(ethylene glycol)) hydrogels can be regulated by changing the concentration, molecular weight and cross-linking density of PEG. According to in vitro cell metabolism and viability tests, the PEG–ADA hydrogels are non-cytotoxic. When placed over a monolayer of myoblasts that were subjected to instantaneous compressive loading, the PEG–ADA hydrogel cushion significantly enhanced cell survival under this deleterious mechanical insult compared with the effects of the conventional PEG hydrogel. Therefore, PEG–ADA hydrogels are promising prosthetic biomaterials for the repair and regeneration of load-bearing tissues. Soft, water-filled polymers known as hydrogels may find roles as implants in load-bearing joints thanks to advances in strain-resistant chemical networks. Most hydrogels contain molecular components called cross-links that connect long polymer chains into a sturdy network. A team led by Bin Li at China’s Soochow University in Suzhou and Liming Bian at the Chinese University of Hong Kong have developed a hydrogel cross-linking system based on a pair of molecules, cyclodextrin and adamantine, that attach to each other using physical forces instead of conventional chemical bonds. When exposed to a mechanical load, these cross-links quickly separate to dissipate energy, then re-associate to preserve the original gel network. Compression experiments revealed the new material could cushion the force applied to mouse muscle cell cultures and reduced cell death rates by 30% compared with conventional hydrogels. This study is to investigate and systemically study the mechanical performance of supramolecular PEG hydrogels in comparison with those of the chemical hydrogels cross-linked by conventional PEG diacrylate (PEGDA). The supramolecular cross-links based on the host-guest complexation significantly enhance the energy dissipation, fatigue resistance, and stress-relaxation of supramolecular PEG hydrogels and protect cells from deleterious mechanical insults. This research provides valuable guidance on the design of prosthetic hydrogels for loading bearing implantations sites with surrounding mechanosensitive cells or tissues and critical insights on the translation of host-guest hydrogels to biomedical applications.