Modular and Photoreversible Polymer–Nanoparticle Hydrogels via Host–Guest Interactions

Abstract Polymer–nanoparticle (PNP) hydrogels are a class of nanocomposite materials showing potential as injectable platforms for biomedical applications. Their design is limited by incomplete knowledge of how the binding motif impacts the viscoelastic properties of the material and is generally constrained to non‐responsive supramolecular interactions. Expanding the scope of available interactions and advancing the understanding of how defined interactions influence network formation would accelerate PNP hydrogel design. To address this gap in the design of PNP hydrogels, the study designs and investigates a tunable platform based on beta‐cyclodextrin (βCD) host–guest cross‐links between functionalized polymers and nanoparticles. A host‐functionalized polymer (βCD hyaluronic acid) and guest harboring block co‐polymer (poly(ethylene glycol)‐ b ‐poly(lactic acid)) NPs are synthesized. The presence and accessibility for binding of the host and guest moieties are characterized via isothermal titration calorimetry. PNP hydrogels with varying concentrations of functionalized polymer and NPs reveal a limited window of concentrations for gelation. It is hypothesized that network formation is governed by the capacity of polymer chains to effectively bridge NPs, which is related to the host–guest ratios present in the system. Further, photo‐responsive guests are incorporated to engineer photoreversible gelation of PNP hydrogels via exposure to specific wavelengths of light.