DNA Hydrogels for Biomedical Applications

DNA hydrogels have emerged as a unique class of programmable biomaterials that harness the molecular recognition, structural versatility, and responsiveness of nucleic acids to create three-dimensional networks suitable for biomedical applications.Their construction strategies can be broadly divided into three categories: pure DNA hydrogels assembled by branched motifs and sticky-end hybridization, hybrid DNA hydrogels integrating synthetic or natural polymers and nanomaterials with DNA cross-linkers, and enzymemediated DNA hydrogels synthesized through rolling circle amplification.These designs provide tunable control over mechanical stability, dynamic responsiveness, and functional incorporation of aptamers, DNAzymes, and immunostimulatory sequences.DNA hydrogels exhibit distinctive properties such as self-healing, shear-thinning, and stimuli-responsiveness toward pH, ligands, light, and nucleases, enabling reversible gel-sol transitions and precise spatiotemporal regulation.Such features underpin their wide-ranging applications in biosensing, drug and gene delivery, tissue engineering, and immunotherapy, where their programmability and biocompatibility offer distinct advantages over traditional hydrogels.Despite these strengths, challenges remain, including limited mechanical robustness, rapid enzymatic degradation in vivo, high synthesis cost, and barriers to clinical translation.Nevertheless, ongoing progress in hybrid material design, chemical modification, and scalable enzymatic synthesis highlights the considerable potential of DNA hydrogels as next-generation platforms for precision medicine and regenerative therapies.