Individually Tailored Modular “Egg” Hydrogels Capable of Spatiotemporally Controlled Drug Release for Spinal Cord Injury Repair

Abstract Controllable drug delivery systems (DDS) can overcome the disadvantages of conventional drug administration processes, such as high dosages or repeated administration. Herein, a smart DDS collagen hydrogel is deployed for spinal cord injury (SCI) repair based on modular designing of “egg” nanoparticles (NPs) that ingeniously accomplish controlled drug release via inducing a signaling cascade in response to external and internal stimuli. The “egg” NPs consist of a three‐layered structure: tannic acid/Fe 3+ /tetradecanol “eggshell,” zeolitic imidazolate framework‐8 (ZIF‐8) “egg white,” and paclitaxel “yolk.” Then NPs served as a crosslinking epicenter, blending with collagen solutions to generate functional hydrogels. Remarkably, the “eggshell” efficiently converts near‐infrared (NIR) irradiation into heat. Subsequently, tetradecanol can be triggered to disintegrate via heat, exposing the structure of ZIF‐8. The Zn‐imidazolium ion coordination bond of the “egg white” is susceptible to cleaving at the acidic SCI site, decomposing the skeleton to release paclitaxel on demand. As expected, the paclitaxel release rate upon NIR irradiation increased up to threefold on the seventh day, which matches endogenous neural stem/progenitor cell migration process. Taken together, the collagen hydrogels facilitate the neurogenesis and motor function recovery, demonstrating a revolutionary strategy for spatiotemporally controlled drug release and providing guidelines for the design of DDS.