For example, maleimide-functionalized Au NPs have been linked to furan-substituted CS through a Diels-Alder reaction producing a hybrid material whose viscoelastic properties demonstrate clearly dependence on the amount of NP used as a multifunctional crosslinker. Similarly, Ag@Lig NPs with oxidized catechol groups at their surface structurally contributed via Michael addition dynamic reactions to the stabilization of a HA-SH hydrogel, while oxidized starch NPs reacted with the amino groups of CMCS leading to the formation of a hybrid with rapid gelling properties well suited to intranasal administration. Crosslinking of PEG-based hydrogels can be achieved by performing coupling reactions between NPs and the PEG end-chains. For instance, cyclooctyne-functionalized PAMAM dendrimers reacted with bis azide-terminated PEG (20 kDa), resulting in a liquid material ideally suited to sustained intratumoral delivery of 5-fluorouracil (5-FU). In a similar manner, the dynamic thiol-disulfide reaction between MSNs and 4-arm-PEG (20 kDa), both thiol-functionalized, resulted in a hydrogel with a 10-fold increase in storage modulus compared with the one containing merely dispersed NPs (i.e., MSN without surface modification), whose strength was due only to the physical adsorption of polymer chains onto the MSNs (Figure ). In addition, the sensitivity of such a crosslinked hydrogel to glutathione (GSH), which led to gradual degradation over 6 weeks, was promising for its potential application as redox responsive drug delivery system. Thiol-functionalization also allowed covalent coupling of MSNs to HAMA ensuring their homogeneous dispersion and avoiding sedimentation and/or phase separation within the matrix. In this example, to achieve the optimal properties crosslinking with a stoichiometric amount of dithiothreitol (DTT) via thiol-Michael reaction was also required (Figure ). Similarly, a hybrid hydrogel was formulated by reacting methylene bisacrylamide, γ-aminobutyric acid, and aminofunctionalized silica NPs of approximately 145 nm in diameter. Herein, the grafting of the NPs on the PAMAM skeleton contributed to the reticulation and allowed to reduce by half the need for additional molecular crosslinker (specifically, pentaethylene hexamine). No additional crosslinker was instead required to form a stable hydrogel when using smaller amino-modified MSNs (22 nm in diameter) and an aldehyde-containing copolymer made of 2-methacryloyloxyethyl phosphorylcholine (MPC) and 4-formylbenzoate ethyl methacrylate (FBEMA). In another example, methacryloil groups present on the surface of MSNs effectively reacted with Gel yielding hybrid hydrogels with overall macroscopic mechanical properties like PEG diacrylate-crosslinked counterparts. All hydrogels proved resistant to excessive compressive strains without fracturing, and were able to recover quickly and completely when subjected to alternately high (250%) and low (0.1%) shear strains.