Injectable Peptide‐Based Functional Amyloid Hydrogels as Tunable Depots for Sustained Drug Delivery

ABSTRACT

Sustained delivery of therapeutic proteins remains a major challenge because rapid degradation and diffusion necessitate frequent dosing, compromising therapeutic efficacy. Here, we present an injectable peptide‐based functional amyloid hydrogel as a versatile drug depot that preserves protein stability while enabling sustained cargo release. As a representative therapeutic application, insulin delivery for diabetes was employed to validate the platform. It exhibited excellent biocompatibility and injectability, providing controlled insulin release over 90 h while preserving its structural stability. Following a single subcutaneous administration in diabetic rats, it restored normoglycemia within 30 min and maintained it for 60 h, followed by a rebound at 66 h, representing a much longer period of glucose maintenance than free insulin. Long‐term in vivo biosafety studies confirmed the absence of systemic toxicity following repeated administration. To demonstrate the tunability of this platform, it was further engineered with sodium alginate as a representative bioadditive, thereby enabling tunable release kinetics and extending sustained insulin release while maintaining injectability and biocompatibility. Collectively, these findings establish peptide‐based functional amyloid hydrogels, either alone or engineered with a bioadditive, as a safe, injectable, and tunable platform for sustained therapeutic delivery, with diabetes serving as a representative proof of concept for broad biomedical applications.