Introduction: Engineering physiologically relevant cell culture substrates requires decoupling multiple environmental cues, such as substrate stiffness and surface topography. Existing hydrogel patterning approaches are limited by complex fabrication, inflexible design space, and feature collapse on soft substrates. Here, we introduce a maskless, contact‑free UV‑sculpting technique that enables fully programmable microscale topographies (from 2 µm to DMD dimensions as the limit) directly onto a wide range of hydrogels, both synthetic (e.g., pAA, pNIPAM, PEG) and natural (GelMA, gelatin), with tunable resolution and topographical amplitude using digital designs and adjustable UV exposure or photoinitiator concentration.
Method: This approach leverages a digital micromirror device (DMD) to project any grayscale mask pattern onto hydrogel surfaces pre-treated with a photoactivator. Within minutes, spatially defined chemical modifications induce sculpting with micrometric fidelity. Feature height or depth (z-scale) can be precisely controlled by varying technique parameters, enabling rapid exploration of design structure relationships across hydrogel properties and physical cues.
Results: As representative benchmarks, GelMA exhibits extrusions of 2.877±0.405 μm and pNIPAM 2.140±0.426 μm, while pAA and PEG show invaginations of 0.117±0.050 μm and 0.286±0.043 μm, respectively, under standard exposure, and GelMA height scales with dose up to 1500 mJ/mm2. Design flexibility is demonstrated with arbitrary shapes and grayscale gradients faithfully reproduced on hydrogels with stiffnesses from ~1.6 to 200 kPa, enabling independent tuning of topography and mechanics.
Conclusions: This technology provides a fast (< 5 min fabrication), digital, versatile, and high‑throughput platform for generating multi‑cue hydrogel substrates. The ability to independently tune mechanical and topographical parameters enables systematic studies in more physiologically relevant microenvironments. Future applications could extend to dynamic platforms, further enhancing spatiotemporal control over cell material interactions.
