Stimuli responsiveness, already discussed for the formulation of the hydrogel, can also be exploited for the design of nanocarriers intended to be incorporated into the matrix. One example of this is the use of PNIPAAm nanogels incorporated into CS hydrogels, which have enabled precise control of drug release by taking advantage of temperature changes. When the temperature exceeded its LCST, the polymer collapsed, allowing the drug (i.e., levofloxacin) to be squeezed out from the carrier and released into the CS matrix. The drug was then gradually released from the hydrogel into the external medium, resulting in a slower and more controlled release rate compared to the aqueous nanogel dispersion. Along with stimuli responsiveness, it has been shown that the overall release rate will be influenced by several parameters such as the porosity of the hydrogel matrix and its chemical composition, which could also result in the establishment non-covalent polymer/drug interactions. Polydopamine (PDA) NPs are an interesting material to achieve precise control on drug release and enhanced residence in situ. For example, 7-ethyl-10-hydroxycamptothecin (SN38)loaded PDA NPs were formulated and covalently linked to thiol-terminated 4-arm-PEG through Michael addition. Under physiological conditions minimal drug release was observed, while after five consecutive min of NIR irradiation the temperature reached approximately 44 °C weakening π-π interactions, responsible for drug adsorption at the NP surface, and making ON/OFF drug release possible (Figure ). Interestingly, in a biomimetic approach, the catechol groups of DA can also endow the materials with mussel-like features and they promote adhesion to a variety of materials/tissues, even under wet conditions. Adapted with permission. Copyright 2017 American Chemical Society.