Photo-induced thiol–ene click chemistry for constructing medical poly(ethylene glycol) hydrogels

Poly(ethylene glycol) (PEG) hydrogels have garnered significant attention in biomedical field due to their good biocompatibility, high water content, and tunable mechanical properties. However, their complex preparation and uncontrollable degradation still require improvement. In this study, photo-induced click chemistry was developed to prepare the medical PEG hydrogels. Linear PEG and tetra-arm-PEG were first functionalized to synthesize vinyl-terminated PEG (PEGDA) and thiol-terminated tetra-arm-PEG (tetra-PEG-SH); hydrogels (PEG−HGs) were subsequently formed between the two components via UV-induced thiol–ene click reaction. The effects of crosslinking density and solid content on the physicochemical properties of the PEG−HGs and lyophilized gels (DPEG−HGs) were investigated. As crosslinking density or solid content increased, the porosity of the DPEG−HGs decreased, while the water retention and compression resistance of the PEG−HGs significantly improved. In vitro drug-release tests indicated that the release rate was closely dependent on the degradation behavior of the hydrogel matrix. By adjusting the solid content of the PEG−HGs, the degradation rate and the duration of sustained drug release could be precisely regulated, achieving prolonged effective drug release over 6−10 weeks. Biological assessments revealed that PEG−HGs possessed > 75% cell survival ratio and < 5% hemolysis rates. The photo-induced click reaction enables simple processing and rapid gelation (< 30 s), yielding hydrogels with tunable mechanical properties, controllable degradation, and outstanding biocompatibility, which show great potential for biomedical applications and offer new insights for designing medical PEG hydrogels.