Significance: Synthetic cellular scaffolds (SCSs) are hydrogels which mimic the extra cellular matrix (ECM) allowing for the study of cellular responses in a controlled environment and the formation of tissues for regenerative medicine. While SCSs can recapture some of the mechanical and physicochemical properties of native ECM, their static properties and poor degradability fail to fully recapture the dynamic nature of the ECM and can harm cells creating a need for new materials. To address these issues, we propose to create novel double stranded DNA based SCSs and subsequently establish cellular compatibility with fibroblasts. Unlike SCSs based on synthetic polymers (e.g. pluronic F127, polyethylene glycol) and biologically derived polymers (e.g. peptides, polysaccharides), dsDNA based materials can be manipulated and degraded in situ with unique chemistries and enzymes which are orthogonal to native ECM and extracellular biomacromolecules. Additionally, cheap and scalable DNA production can allow for bulk scale (10 - 1000 mg) material production, opening the door to new applications beyond being the stuff of genetic information.
