Hydrogen-bond interfacial engineering of silk fibroin-strengthened magnetic colloidal hydrogel for embolization and magnetothermal therapy of hepatocellular carcinoma.

Injectable hydrogels adapt to vascular shapes and block blood flow effectively, enabling wide application in the transcatheter arterial embolization (TAE) of hepatocellular carcinoma (HCC). However, balancing facile injectability and high mechanical robustness is challenging, as optimizing one compromises the other. Colloidal hydrogels achieve injectability via bottom-up assembly but have limited mechanical properties due to insufficient interface design. Herein, we report a hydrogen-bond interfacial strengthening strategy into the electrostatically crosslinked colloidal network to develop an injectable and mechanically stable magnetic colloidal hydrogel, which is assembled from electronegative hydrogen bond-rich silk fibroin iron oxide nanoparticles (SF@Fe3O4 NPs) and electropositive Gelatin NPs. This SF@Fe3O4 magnetic colloidal hydrogel (SF-MCH) can be injected through a medical microcatheter with an injection force of ∼10 N, which is only 15% of the manual limit. The storage modulus of SF-MCH (∼900 Pa) was three times higher than those of the PAA@Fe3O4 and Na3Cit@Fe3O4 magnetic colloidal hydrogels, meeting the mechanical performance requirements for embolization (>800 Pa), owing to the colloid interfacial hydrogen-bond interactions demonstrated by variable-temperature fourier transform infrared spectroscopy. Compared to gelatin bulk hydrogel containing SF@Fe3O4 NPs (SF-MBH), SF-MCH showed superior self-healing efficiency (94%) and shape fidelity. Additionally, SF-MCH could withstand pressures up to 36 kPa, well above physiological vascular pressure of 16 kPa. Furthermore, SF-MCH mediated embolization combined with magnetic hyperthermia significantly inhibited rabbit ear tumors, while SF-MCH achieved sustained renal artery embolization in rabbits. This hydrogen-bond interfacial reinforcing strategy brings a feasible route for the design of colloidal hydrogels with robust mechanics and tailor-made functionality.