Sea Cucumber-Inspired Autolytic Hydrogels Exhibiting Tunable High Mechanical Performances, Repairability, and Reusability

Inspired by stimuli-responsive remarkable changes in consistency (hardening, softening, autolysis) of sea cucumbers, we synthesized a supramolecular polymer­(SP) hydrogel directly by photoinitiated aqueous polymerization of N-acryloyl 2-glycine monomer bearing one amide and one carboxyl group on the side chain. The SP hydrogels doped with Ca²⁺ demonstrated excellent mechanical properties–high tensile strength (∼1.3 MPa), large stretchability (up to 2300%), high compressive strength (∼10.8 MPa), and good toughness (∼1000 J m^–2) due to cooperative hydrogen bonding interactions from amide and carboxyl together with Ca²⁺ cross-linking. Responding to the change in pH and Ca²⁺ concentration, the hydrogels could modulate their network stability and mechanical properties: at pH3.0 and higher Ca²⁺ content, the hydrogel formed low swelling network which was stiff and stable; in alkaline or neutral buffer with lower content of or without Ca²⁺, the hydrogel formed a highly swollen transient network, which was soft and eventually autolyzed. The reversible multiple noncovalent bonds enabled the hydrogels to achieve thermoplasticity, self-healability, and reusability. Notably, distinct formulations of hydrogels could be welded together under heating to form a gradient hydrogel. In vitro cytotoxicity assay and subcutaneous implantation indicated that the SP hydrogels were biocompatible and autolytic in vivo. The SP hydrogels may find applications as temporary biodevices for intestinal drug delivery or for injectable filling in assisting suturing small vessels.