Fabricating Tough Interpenetrating Network Cryogels with DNA as the Primary Network for Biomedical Applications

This work investigates a sequential strategy to develop DNA-based hydrogel scaffolds with interpenetrating polymeric network. The scaffolds were formed via a two-step procedure. First, a covalently cross-linked DNA-based cryogel was formed by the chemical reaction between DNA strands and a bifunctional cross-linker, polyethylene glycol diepoxide at subzero temperatures. In the second step, alginate chains were absorbed into the preformed macroporous DNA cryogel network, followed by ionic cross-linking with divalent calcium ions. The individual and synergistic effects of covalent and ionic cross-linkings on mechanical and physical properties of the IPN cryogel were tested. The IPN cryogels were able to sustain large deformations higher than 95% of strain under compressive forces without exhibiting any failure. Addition of a physically cross-linked alginate network to the covalently linked DNA cryogel significantly enhanced its toughness and energy dissipation compared to the covalent network alone. The formulated hydrogels also exhibited excellent biocompatibility with human stem cells. Overall, this DNA-based IPN cryogel has the potential to be used as a biomaterial scaffold for a diverse range of tissue engineering applications.