In the biomaterials field, one major issue with hydrogels (HGs) loaded with active therapeutics is the spontaneous leaking of the cargo occurring rapidly, usually over several hours. However, biological processes involved in regenerative medicine would require to have a sustained drug delivery lasting over weeks/months or be triggered only when a specific biochemical stimulus (enzymatic, cellular, or antimicrobial) is applied. In this work, this challenge is addressed by demonstrating that the spontaneous protein release from an agarose HG (used as model HG) can be partially or totally blocked by the incorporation of stellate mesoporous silica (STMS) nanoparticles (NPs, ≈150 ± 28 nm size, 15 nm pore) within the HG. It is shown here that the porous silica NPs act as sub-micrometer size reservoirs ensuring precise level retention simply by playing on the amount of STMS embedded in the HG. Further, this effect is shown for various proteins demonstrating the versatility of this concept.