and NIPAAm copolymer ((PNIPAAm-co-PGMA)-b-PS NPs) were found to improve the mechanical properties of a hydrogel made of PNIPAAm and PDA. The NPs acted as a dynamic crosslinking core leading to the establishment of hydrogen bonds and hydrophobic ππ interactions (Figure ) whose sacrificial nature enhanced the mechanical properties of the hybrid material, resulting in twice the maximum tensile strength and up to six times higher maximum compressive strength compared to the hydrogel without NPs. When stress is applied, these bonds preferentially break, absorbing some of the impact energy and improving the hybrid hydrogel ability to resist deformation. Entropy-driven stable physical hydrogels have been formulated blending a hydrophobic derivative of the HPMC-C12 and highly concentrated PLA-based NPs (stock formulation up to 200 mg mL -1 , final concentration in the gel 10% w/v). Following administration, these hydrogels acted as prolonged depots for the delivery of various macromolecules including cytokines, CD40 agonist antibodies, and vaccine components dispersed within the hydrogel matrix. The same modification approach was also applied to HA, using C8-12 chains, and it resulted in a material suitable for the delivery of two different cytokines loaded either in the hydrogel matrix (i.e., fragment of hepatocyte growth factor) and in the NP core (i.e., engineered stromal cell-derived factor 1α (SDF-1).