A similar phenomenon has been exploited to enhance the bulk mechanical properties of polysaccharide-based, physically crosslinked hydrogels by incorporating drug-loaded poly(lactic- co-glycolic acid) microspheres into the hydrogel formulation 29, 30. More recently, NP adsorption to polymer gels has been exploited to achieve strong, rapid adhesion between disparate gels 25. For example, complementary affinity between polymers (molecular binders) and the surface of hard NPs (clay nanosheets/silicates) has been utilized to fabricate high-water-content and mouldable hydrogels 24, 26, 27, 28. Within the field of self-assembly, polymer–nanoparticle (NP) interactions have arisen as a simple route to assemble tunable and self-healing polymeric materials without the need for complex synthetic approaches or specialized small-molecule binding partners 24, 25. However, the shear-thinning and self-healing hydrogels presented to date are limited by poor mechanics and slow self-healing or require challenging, costly and poorly scalable synthesis of macromolecular components through protein engineering or complex, multi-step chemical functionalization.Ĭrucial requirements to the biomedical translation of mouldable and injectable hydrogels are facile and mild formation, modular modification and finely tunable control over mechanical properties, as well as rapid self-healing following injection. In each of these examples, self-assembly of functional materials via non-covalent, intermolecular interactions with dynamic and reversible macroscopic behaviour was exploited. Several systems have been reported utilizing natural host–guest or receptor–ligand pairs, such as (strep)avidin with biotin 11, 12, leucine zipper 13, 14 and ‘dock-and-lock’ 15, 16 protein structures prepared with genetic engineering techniques, or with synthetic macrocyclic host molecules, such as cyclodextrins 17, 18 or cucurbiturils 19, 20, 21, 22, 23. Self-assembly via non-covalent crosslinking provides a route to fabricate mouldable and injectable hydrogels with shear-thinning and self-healing properties arising from strong, yet transient and reversible crosslinks 2, 10. These properties enable minimally invasive implantation in vivo though direct injection or catheter-based delivery, contributing to a rapid gain in interest in their use for controlled drug delivery 10. In addition, it is extremely beneficial if the high shear viscosity is low for facile application through high gauge needles. To serve these functions, mouldable hydrogels must exhibit viscous flow under shear stress (shear-thinning) and rapid recovery when the applied stress is relaxed (self-healing). Mouldable hydrogels that can be formed and processed prior to use and subsequently applied in a conformal manner provide attractive alternatives to covalent hydrogels for many applications, including local drug delivery in the body, cell carriers for tissue engineering, bone fillers or hydraulic fracturing fluids. These covalently crosslinked hydrogels form robust, tough and elastic materials however, they can be limited by the irreversibility of their crosslinks. Many hydrogel systems utilize covalent crosslinking approaches 5, including radical processes initiated by light 6, 7, temperature 8 and pH 9. Hydrogels comprise an important class of material well-suited for a range of applications on account of their high water content and highly tunable mechanical properties 1, 2, 3, 4. The work introduces a facile and generalizable class of mouldable hydrogels amenable to a range of biomedical and industrial applications. Owing to the hierarchical structure of the gel, both hydrophilic and hydrophobic drugs can be entrapped and delivered with differential release profiles, both in vitro and in vivo. We develop a physical description of polymer–NP gel formation that is utilized to design biocompatible gels for drug delivery. The transient and reversible interactions between biopolymers and NPs enable flow under applied shear stress, followed by rapid self-healing when the stress is relaxed. Biopolymer derivatives are linked together by selective adsorption to NPs. Here we report a new paradigm for the fabrication of self-assembled hydrogels with shear-thinning and self-healing properties employing rationally engineered polymer–nanoparticle (NP) interactions. Mouldable hydrogels that flow on applied stress and rapidly self-heal are increasingly utilized as they afford minimally invasive delivery and conformal application.
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