Designing soft materials that can autonomously respond to complex physiological environments remains a fundamental challenge in biomedical systems engineering. This paper introduces a 3D-printed hybrid protein-polymer hydrogel actuator that operates through endogenous biochemical logic, achieving fully autonomous, two-stage shape transformation and enzyme-triggered drug release in a simulated gastric environment. The actuator consists of a bilayer structure: an active layer made of 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 due to pepsin-mediated degradation, autonomously driving reversible shape change without manual intervention. By embedding doxorubicin (DOX) into the BSA-PEGDA hydrogel network, the system achieves enzyme-gated drug release at a specific site and can be regulated using peptide A as a biochemical inhibitor. High-resolution digital light processing (DLP) printing enables the fabrication of complex autonomous actuators and microneedle-equipped grippers, which can achieve mucosal adhesion, capture and release behaviors, and controlled delivery. This study establishes a materials design strategy that uses biochemical cues as programmable inputs to drive mechanical and therapeutic outputs, providing a solid platform for bioresponsive soft robotics and in situ drug delivery.

Summary

This Advanced Materials cover highlights a breakthrough: a smart hydrogel that "understands stomach signals." Researchers at the Technion-Israel Institute of Technology leveraged bovine serum albumin (BSA)’s dual responsiveness to gastric acid and pepsin, combined with 3D printing, to create a bilayer hydrogel actuator. In the stomach’s acidic environment, BSA structural changes drive rapid bending for grasping; later, pepsin acts as a "biological key," gradually degrading the protein network to soften and reset the material, enabling autonomous "grasp-release" cycles—all controlled by intrinsic biochemical signals without external intervention. More innovatively, they integrated the anticancer drug doxorubicin (DOX) into the system, achieving a "smart device" combining shape change and drug delivery. During bending, drugs are securely locked; only when pepsin degrades the material does DOX release intensively. This precise "locate-then-release" timing control, like an autonomous micro-robotic pharmacist in the stomach, offers new solutions for targeted gastric therapy and sustained drug release, marking a key step toward higher autonomy and intelligence in bioresponsive materials.

References:

DOI: 10.1002/adma.202516809