# Mechanical Properties of DNA Hydrogels: Towards Highly Programmable Biomaterials
## 6 Mimicking Biomaterials for Biomedical Applications  
The inherent biocompatibility of DNA-based biomaterials and the control over the mechanical properties provide DNA-based hydrogels with several advantages over other biomaterials, such as hydrogels assembled from ECM-derived proteins, polysaccharides, and natural or synthetic polymers [138; 139]. These are commonly used to control cellular behaviors and create ECM mimics or scaffolds for biomedical application such as regenerative medicine, tissue engineering, sustained drug delivery [140], immunomodulation [41; 141], and wound healing [142]. Indeed, the nanoscale precision for biomolecules' conjugation and the ease of DNA motifs' functionalization have enabled the assembly of hybrid biomaterials conjugated with several bioactive signals such as ECM-cell adhesion peptides and growth factors [143; 144], or antigens, and immunomodulatory motifs [41; 42], which can facilitate cell interactions and induce control of cell behaviors [145]. For example, [PERSON] et al. designed a multiligand DNA origami for the pathway-specific modulation of neocortical neurons while monitoring local membrane tension with a DNA-based FRET tension sensor [136]. Alternatively, in a study by [PERSON] et al. the authors designed DNA-based ribbons to assemble a fiberlike ECM mimicking biomaterial that was later functionalized with ECM proteins--containing the RGD peptide--in order to promote cell attachment [46]. Another strategy was developed by [PERSON] et al. to assemble a printable peptide-DNA hybrid biomaterial generated using PCR with branched primers that can serve as a coating layer to promote cell attachment on the surface [146]. These materials show that cells can adhere, grow, and proliferate on DNA-based hydrogels. DNA-based biomaterials also appear to be well-suited for the sustained release of drugs or antigens. [PERSON] et al. notably used injectable DNA-based hydrogels loaded with the ovalbumin model antigen and CpG motifs to induce a strong immune response in mice [43]. In another study, [PERSON] et al. developed a hybrid DNA/RNA hydrogel that can stimulate Toll-like receptors (TLR) by releasing GU-rich RNA sequences and inducing a strong immune response [40]. Several studies have also highlighted the use of DNA-based materials or hybrid DNA materials with controlled and tunable mechanical and rheological properties to mimic those of the ECM and influence cell behavior. For instance, using DNA oligonucleotides as a linker for a polyacrylamide gel functionalized with ECM proteins, [PERSON] et al. have notably demonstrated that they could control the gel stiffness from a few hundred Pa to 30 kPa by varying the length and density of the crosslinker strands [147]. They showed that temporally altered mechanical properties influenced the length and number of dendrites of neurons cultured on their hydrogels. [PERSON] et al. have shown that incorporating silicate nanodisks into DNA-based hydrogels could enhance toughness and elasticity and serve as good ECM mimics for tissue repair with sustained drug delivery capability [148]. These works highlight the potential of DNA-based hydrogels for functional tissue engineering with a broad array of stimuli-responsiveness [149].