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Hydrogels are promising candidates for recapitulation of the native extracellular matrix (ECM), yet recreating molecular and spatiotemporal complexity within a single network remains a challenge. Double network (DN) hydrogels are a promising step towards recapitulating the multicomponent ECM and have enhanced mechanical properties. Here, we investigate DNs based on dynamic covalent and covalent bonds to mimic the dynamicity of the ECM and enable biofabrication. We also investigate the spatiotemporal molecular attachment of a bioactive adhesive peptide within the networks. Using oxidized alginate (dynamic network, Schiff base) and polyethylene glycol diacrylate (static network, acrylate polymerization) we find an optimized procedure, where the dynamic network is formed first, followed by the static network. This initial dynamically cross-linked hydrogel imparts self-healing, injectability, and 3D printability, while the subsequent DN hydrogel improves the stability of the 3D gels and imparts toughness. Rheology and compression testing show that the toughening is due to the combination of energy dissipation (dynamic network) and elasticity (static network). Furthermore, where we place adhesive sites in the network matters; we find distinct differences when an adhesive peptide, Arg-Gly-Asp (RGD), is attached to the different networks. This DN strategy bring us closer to understanding and recreating the complex multicomponent ECM-pushing us past a materials view of cell adhesionwhile enabling injectabiltiy and printing of tough hydrogels.

Polymer materials are indispensable in our daily lives. This makes polymer technology of critical importance in higher education. In particular, hands-on experiment-based practicals/laboratories with a focus on polymer science are of tremendous value in the undergraduate curriculum. Along these lines, hydrogels are highly cross-linked polymer networks which show some unique properties such as water absorbance and large extensibility, making them particularly well-suited in various biomedical applications. The properties of hydrogels can be systematically varied via changes in composition. In this practical laboratory, we use hybrid hydrogel formulations containing alginate and polyacrylamide to explore the consequences of compositional changes on mechanical behavior. Mechanical properties are determined using a simplified tensile test that is amenable to large groups of students using standard laboratory equipment. We used marbles to induce an extensional force and a ruler to measure the elongation of the gel as a function of the attached weight. Hereby, stress−strain curves can be obtained, and students are able to compare the difference between single and double network hydrogels as well as quantify the influence of network composition. This practical combines the use of chemical synthesis (i.e., reactant calculations) with practical skills which makes it interesting to use in a third year chemical/ biomedical course. Furthermore, students can learn how to deal with chemicals and gain insight in polymer chemistry and its wide applicability, making it particularly well-suited for students coming from outside the traditional chemical science background.

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Compositional changes in the chemical makeup of hydrogels offer a powerful strategy for fine tuning of mechanical properties, enabling specific targeting for different applications. The chemical versatility exhibited by the tunable system introduced here can be leveraged to address a broad range of characteristics across the field of tissue engineering�from blood vessels to cartilage, for example�which demands materials with very different mechanical profiles. Furthermore, we rely exclusively on dynamic, non-covalent cross-linking to provide opportunities for 3D printing and injectability. This work describes a highly tunable system based on hydrogen bonding and ionic interactions. Single network hydrogels were made by exploiting various acrylic monomers including N-acryloyl glycinamide (NAGA) and acrylic acid (AAc). Additionally, hybrid hydrogels were explored by combining these acrylic networks with an ionically cross-linked alginate network. By combining orthogonal cross-linking strategies and altering the ratio between different components in these hybrid gels, a broad range of mechanical properties is demonstrated. The characteristics were extensively investigated using tensile testing, compression testing, and rheological measurements. The final scaffolds were also shown to be non-cytotoxic in preliminary cell viability studies for human dermal fibroblasts.