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

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.