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bioRxiv · 10.64898/2026.03.10.710804

Self-Terminating Bilayer Hydrogel Actuators via Enzyme-Programmed Mechanical Feedback

Mo, F.·Bar-Shalom, G.·Gozlan, E. S.·Liu, Y.·Sosnik, A.·Khoury, L. R.
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Abstract

Autonomous soft materials that can actuate, perform a function, and then self-terminate without external intervention remain difficult to realize. Here, a bilayer hydrogel actuator fabricated by digital light processing-based 3D bioprinter is introduced that couples rapid thermoresponsive deformation with slower enzyme-programmed mechanical feedback to achieve self-regulated shape transformation and autonomous recovery. The system integrates a poly(N-isopropylacrylamide) actuation layer with a bovine serum albumin-poly(ethylene glycol) diacrylate enzyme-programmed layer loaded with trypsin. Above the lower critical solution temperature, deswelling of the actuation layer generates a strain mismatch across the bilayer and drives rapid closure. In parallel, proteolytic cleavage of albumin domains progressively softens the enzyme-programmed layer, reduces interlayer constraint, and acts as an intrinsic mechanical off-switch that relaxes curvature and restores the open state. This materials logic enables sustained enzyme release, time-dependent modulus loss, and autonomous shape recovery without staged external triggers. As a proof-of-concept, this platform is implemented as a gastrointestinal-retentive hydrogel gripper for localized intestinal enzyme delivery, where it exhibits thermally triggered gripping, millinewton-scale gripping force, autonomous reopening, and robust ex vivo retention on porcine small intestine under dynamic motion. These findings establish enzyme-programmed mechanical feedback as a general design strategy for self-regulated soft actuators and therapeutic materials with built-in functional lifetimes.

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Mo, F., Bar-Shalom, G., Gozlan, E. S., Liu, Y., Sosnik, A., Khoury, L. R.. 2026-03-12. Self-Terminating Bilayer Hydrogel Actuators via Enzyme-Programmed Mechanical Feedback. https://doi.org/10.64898/2026.03.10.710804

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