Host–Guest Chemistry for The Design of Functional Polymer–Nanoparticle Hydrogels

Polymer–nanoparticle (PNP) hydrogels are a class of injectable nanocomposites based on physical interactions between polymers and nanoparticles (NPs). (1) Due to the shear-thinning and self-healing behaviour provided by the reversibility of the polymer–nanoparticle interactions, they have been used in the biomedical field as injectable biomaterials or inks for additive manufacturing. (2-3) Current PNP hydrogels however cover a narrow range of functionality and can be built from a restricted pool of available building blocks due to the constraint presented by the limited versatility of the cross-linking interactions. Here, we present the use of a supramolecular motif based on host–guest interactions for the design of versatile and functional PNP hydrogels.<br/><br/>In this work, two approaches based on cyclodextrin (CD) host–guest interactions were used for the design of PNP hydrogels. In a first approach, alpha-cyclodextrin (αCD) was added to a cellulose- and PEGylated-NP-based hydrogel, to decouple mechanical properties from building blocks via polypseudorotaxane formation. The addition of αCD enabled the exchange of the polymer and nanoparticle for varied biopolymer with secondary cross-links or inorganic nanoparticles with conductive or magnetic characteristics. In a second approach, beta-cyclodextrin (βCD) was used in combination with azobenzene, a photo-responsive guest for the design of light sensitive hydrogels. For this purpose, a host-functionalized polymer (β-CD hyaluronic acid) and guest harboring block copolymer (PEG-<i>b</i>-PLA) NPs were synthesized.(5) The presence of the photoresponsive host–guest complex resulted in reversible gelation of the hydrogel via illumination at various wavelengths of light. This work demonstrates how supramolecular interactions can be used to engineer versatile and functional polymer nanocomposite biomaterials and substantially increase the utility of this class of materials.<br/><br/>(1) E. Appel, M. W. Tibbitt et al. (2015) <i>Nature Communications</i>, 6:6295.<br/>(2) E. A. Guzzi et al. (2019) <i>Small</i>, 15, 1905421.<br/>(3) E. A. Guzzi et al. (2021) <i>Biofabrication</i>, 13, 044105.<br/>(4) G. Bovone, E. A. Guzzi, S. Bernhard et al. (2021) <i>Advanced Materials</i>, 2106941.<br/>(5) S. Bernhard et al. <i>in preparation</i>