Bioactive DNA hydrogel interfacing with living cells and extracellular vesicles

Abstract

Biological vesicles, such as living cells and extracellular vesicles (EVs) in biological systems, are the important agents and regulators of life functions, which play an irreplaceable role in physiological processes and disease progression. The maintenance of high bioactivity and structural integrity and 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 the material constructed by hydrogel with bioactive molecules, which simulated the living systems in vitro. By utilizing the unique molecular recognition and sequence programmability of deoxyribonucleic acid (DNA), DNA containing multifunctional modules is regarded as the material chemistry basis. Through molecular design and functional units incorporation, these strategies enable the construction of DNA hydrogels capable of targeted vesicle recognition. This review provides the interactions between DNA hydrogel 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 EVs isolation, cell engineering and three-dimentional (3D) culture, disease detection, and disease treatments. First, the interaction and controllable release mechanisms of bioactive DNA hydrogels are summarized, and the relative researches based on mechanisms are reviewed. Next, the pioneering work in biomaterial applications are summarized. Finally, it is concluded with the challenges of DNA hydrogel facing with, and the future prospects of bioactive DNA hydrogels.