Bioactive DNA hydrogel interfacing with living cells and extracellular vesicles

Biological vesicles, such as living cells and extracellular vesicles (EVs) in biological systems, are important agents and regulators of life functions and play an irreplaceable role in physiological processes and disease progression. The maintenance of high bioactivity and structural integrity as well as selective isolation of target biological vesicles from complex biological systems are of great significance for downstream applications, such as early diagnosis, treatment and prognostic monitoring of major diseases. Bioactive hydrogel is a material made of hydrogel containing bioactive molecules that simulate living systems in vitro. By exploiting the unique molecular recognition and sequence programmability of deoxyribonucleic acid (DNA), DNA containing multifunctional modules serves as the material chemistry basis. Through molecular design and functional unit incorporation, these strategies enable the construction of DNA hydrogels capable of targeted vesicle recognition. This review discusses interactions between DNA hydrogels and biological vesicles, focuses on controllable release mechanisms of vesicles, and highlights recent advances in biomedical applications boosted by bioactive DNA hydrogels, including cell and EV isolation, cell engineering and three-dimensional (3D) culture, disease detection, and disease treatments. First, the interaction and controllable release mechanisms of bioactive DNA hydrogels are summarized, and relevant research based on these mechanisms is reviewed. Second, pioneering work in biomaterial applications is summarized. Finally, it is concluded with the challenges faced by DNA hydrogels and the future prospects of bioactive DNA hydrogels.