ABSTRACT Designing soft materials that autonomously respond to complex physiological environments remains a fundamental challenge in biomedical systems engineering. Here, we report on a 3D‐printed hybrid protein‐polymer hydrogel actuator that operates via endogenous biochemical logic , enabling fully autonomous dual‐stage shape morphing and enzyme‐triggered drug release in gastric‐mimicking environments. The actuator comprises a bilayer structure: an active layer based on bovine serum albumin‐poly (ethylene glycol) diacrylate (BSA‐PEGDA), and a passive PEGDA layer. In acidic gastric fluid, the BSA‐PEGDA layer undergoes rapid conformational swelling, followed by delayed softening from pepsin‐mediated degradation, autonomously driving reversible shape transitions without manual intervention. By embedding doxorubicin (DOX) within the BSA‐PEGDA hydrogel network, the system achieves site‐specific, enzyme‐gated drug release that is tunable using pepstatin A as a biochemical inhibitor. High‐resolution digital light processing (DLP) printing enables the fabrication of complex autonomous actuators and microneedle‐equipped grippers capable of mucosal adhesion, catch‐and‐release behavior, and controlled delivery. This work establishes a materials design strategy where biochemical cues are used as programmable inputs to drive mechanical and therapeutic outputs, offering a robust platform for bioresponsive soft robotics and in situ drug delivery.
Liu et al. (Wed,) studied this question.