Charge-neutralized anti-swelling hydrogels enable mechano-curvature-coupled microphysiological system

Curvature topography and mechanical stimulation are key biophysical cues in the tissue microenvironment that play critical roles in regulating cell behavior. However, the stable construction of curved structures and the application of dynamic mechanical loading in ultrasoft biomaterials remain challenging, limiting the reconstruction of microenvironments for soft tissues such as the lung. Here, we propose a charge-neutralization anti-swelling hydrogel strategy. By introducing LiCl, Li⁺ ions electrostatically shield and coordinate with fixed negative charges, thereby suppressing the Donnan effect to inhibit hydrogel swelling and enhance structural stability. The resulting hydrogel exhibits a tunable Young's modulus ranging from 1.12 to 339.79 kPa. Combined with three-dimensional (3D) printing, biomimetic curved structures with curvatures ranging from 10^-4 to 4 × 10^-2 μm^-1 were stably fabricated. Integration with a stretching driver further enabled controllable cyclic stretching (0∼40%), establishing a microphysiological system that couples curvature topography with mechanical cues and recapitulates the physiological and pathological parameters of multiple tissues. Curvature topography and mechanical stimulation significantly influenced tissue phenotypes, including surfactant secretion, proliferation, and migration, as well as drug sensitivity. This work provides a general design strategy for reconstructing complex tissue microenvironments and establishes a more physiologically relevant platform for investigating tissue development, disease mechanisms, and drug responses.