Abstract

Expandable shape‐morphing hydrogels that ensure prolonged site residence, have tailored mechanical integrity and tunability, are biocompatible to minimize side effects and can release drugs over an extended time remain challenging to achieve. Herein, a new class of enzyme‐triggered bovine serum albumin and polyethylene glycol diacrylate hybrid hydrogels is presented, contributing to advancements in controlled drug‐model release and actuation. These hydrogels combine the intrinsic properties of proteins with the resilience of synthetic polymers, offering a versatile application platform. Central to our research is the trypsin‐induced simultaneous functionality of controlled drug model release and dynamic shape changes under physiological trypsin concentrations (0.01% w/v). These hydrogels display tailored mechanical and physical properties and microstructure, which are crucial for biomedical devices, soft robotics, and tissue engineering applications. Additionally, the hydrogels effectively control the release of fluorescein isothiocyanate, a model drug, indicating their potential for highly targeted drug delivery, particularly in the gastrointestinal tract. The study also highlights the significant effect of shape‐morphing on drug release rates under physiological trypsin concentrations. These findings suggest that enzyme‐responsive hybrid protein‐polymer hydrogel actuators with tailored mechanical and physical properties can enhance the precision of drug delivery in biomedical applications.

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