Supramolecular Reinforcement of Polymer–Nanoparticle Hydrogels for Modular Materials Design

Moldable hydrogels can flow under applied stress (shear-thin) and reform a stable network (self-heal) when the stress is removed. An emerging class of moldable biomaterials are polymer–nanoparticle (PNP) hydrogels, which are formed from reversible intermolecular interactions between polymer chains and nanoparticles.¹ PNP hydrogels are used as injectable or extrudable materials in biomedical and industrial applications, however, the mechanical properties of PNP hydrogels are limited and network formation is restricted to interactions between specific combinations of polymer chains and nanoparticles.²^–4<br/><br/>In this study, we developed a simple strategy to reinforce PNP hydrogels and expand the application spectrum of this class of materials.⁵ We included α-cyclodextrin (αCD) in the hydrogel formulation as a supramolecular motif enabling mechanical reinforcement and modular design. Rheological measurements demonstrated that the addition of αCD improved the mechanical stability of PNP (CD–PNP) hydrogels in a concentration-dependent manner, achieving storage moduli up to G′ ≈ 10 kPa (ω = 1 rad s^-1). The tested formulations retained the ability to shear-thin and self-heal. Our hypothesis is that mechanical reinforcement was caused by threading of αCD onto PEGylated nanoparticles and polypseudorotoxane formation, which enhanced nanoparticle–nanoparticle interactions.^6,7 We further leveraged these interactions to decouple mechanical properties from material functionality. We exchanged the structural polymers (hydroxypropylmethylcellulose, collagen, alginate, and methacrylated hyaluronic acid), and nanoparticles (block copolymer nanoparticles, gold nanoparticles, and iron nanoparticles), forming stable hydrogel networks (tan δ &lt; 1, ω = 1 rad s^-1) that were not possible to be fabricated without CD-reinforcement. CD–PNP formulations showed improved properties and tunability for 3D bioprinting and drug delivery applications and the application spectrum of this class of materials was broadened to electroconductive and magnetic applications.<br/><br/>Overall, supramolecular reinforcement improved PNP hydrogel mechanical properties and broadened the application spectrum without the need to re-engineer the network interactions. Reinforced CD–PNP hydrogels are a useful platform for applications where moldability, mechanical strength, and functionality are needed.<br/><br/><i>References:</i><br/>[1] Appel, E. A., Tibbitt, M. W. et al. <i>Nat. Commun.</i> 6, 6295, (<b>2015</b>)<br/>[2] Fenton, O. S. et al. <i>Biomacromolecules</i> 20, 4430–4436, (<b>2019</b>)<br/>[3] Stapleton, L. M. et al. <i>Nat. Biomed. Eng.</i> 3, 611–620, (<b>2019</b>)<br/>[4] Guzzi, E. A. et al. <i>Small</i> 15, 1905421, (<b>2019</b>)<br/>[5] Bovone, G., Guzzi, E. A., Bernhard, S. et al. <i>Adv. Mater. </i>34<i>,</i> 2106941, (<b>2021</b>)<br/>[6] Harada, A. et al. <i>Nature</i> 370, 126–128, (<b>1994</b>)<br/>[7] Liu, K. L. et al. <i>Soft Matter</i> 7, 11290–11297, (<b>2011</b>)