Decoupling Injectability and Molecular Confinement via Jammed PEG Nanogels

Long-acting local delivery of small-molecule drugs faces a trade-off: reducing hydrogel mesh size to restrict rapid diffusion drastically increases viscosity and injection force. To overcome this, we introduce INJECT, a platform based on the hierarchical jamming of dense PEG nanogels. This system decouples molecular confinement within individual nanogels from macroscopic flow. At high packing densities, nanogel deformation eliminates interstitial voids that would otherwise allow rapid drug diffusion. To preserve injectability, a minority of ultrasoft nanogels is integrated to act as defects, promoting localized yielding and drastically reducing injection force under shear. This strategy enables injectable hydrogels with molecular-scale confinement for sustained small-molecule retention.