Dual-cross-linked network (DCN) hydrogels with multiresponsive and self-healing properties are attracting intensive interests due to their enhanced mechanical strength for a wide range of applications. Herein, we developed a DCN hydrogel that combines a dynamic imine and a benzoxaboronic ester with a neutral pK a value (∼7.2) as dual linkages and contains biocompatible zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) [poly(MPC)] as the backbone. Oscillatory rheology result indicated shear strengthening mechanical properties compared to the singlecross-linked network (SCN) hydrogels, which use either imine bond or benzoxaboronic ester as the linkage alone. Due to the coexistence of stimuliresponsive imine and benzoxaboronic ester, the DCN hydrogels show sensitive multiple responsiveness to pH, sugar, and hydrogen peroxide. The dynamic nature of the dual linkages endows the DCN hydrogels with excellent self-healing ability after fracture. More importantly, the excellent biocompatibility and performance in three-dimensional (3D) cell encapsulation were established by a cytotoxicity Live/Dead assay, indicating DCN hydrogel's great potential as a cell culture scaffold. The biocompatible poly(MPC)-based backbone and the rapid formation of the cross-linking network make the DCN hydrogels promising candidates for future biomedical applications.

We report here the synthesis of a series of ethylene glycol-based triblock copolymers containing a hydrophilic middle segment of poly­(ethylene glycol) methyl ether methacrylate (PEGMA) and two temperature-responsive segments of diethylene glycol methyl ether methacrylate (DEGMA) at both ends via the reversible addition-fragmentation chain-transfer (RAFT) polymerization. While the corresponding temperature-responsive homopolymer (PDEGMA) and the diblock copolymer (PDEGMA-b-PPEGMA) could not form a gel, the triblock copolymers (PDEGMA-b-PPEGMA-b-PDEGMA) could form a physical gel at certain concentrations and at temperatures above the lower critical solution temperature (LCST). This sol–gel transition is fully reversible and can be repeated several times. Depending on the chain length of the middle block and two end blocks, a physical gel could be formed at a minimum polymer concentration of 5 wt %. In addition, a mechanically strong gel could be easily formed within 5 s at the maximum concentration of 20 wt % and at a temperature of 37 °C. Considering the good cell compatibility and soft rubbery nature of the triblock copolymers, they can potentially be used as injectable scaffold for cell culture and tissue engineering applications.

Hypoxia-activated prodrugs (HAPs) have emerged as important candidates for chemotherapy due to their efficient killing of hypoxic cancer cells. Traditional small molecule agents, such as tirapazamine (TPZ) and its derivatives, have shown unsatisfactory therapeutic effect in clinical trials due to poor bioavailability in hypoxic tumor regions. Herein, an amphiphilic macromolecular prodrug with hypoxia-specific activity, named as hypoxia-activated macromolecular prodrug (HAMP), is prepared from poly{[poly(ethylene glycol) methacrylate]-st-(methacrylic acid)} [poly(PEGMA-st-MAA)], containing pendant TPZ residues. This polymer can self-assemble in an aqueous system into ∼37 nm sized nanoparticles. In vitro experiments indicated that HAMP shows 5× higher cytotoxicity to hypoxic cancer cells as compared to normoxic cancer cells. Therefore, the developed HAMP can be concurrently used with other therapeutic agents as a highly efficient hypoxia-activated agent.