Exploration Of Biomedical Applications Based On DNA Supramolecular Hydrogels

The extracellular matrix(ECM)is well known for its ability to provide structural environment for hosting the cells,as well as combine the biophysical and biochemical signals for regulating the cells behavior.Thus,the ECM plays an important role in maintaining the basic cellular functions,modulating the tissue morphogenesis or organization,and enhancing the tissue functions.Recently,a variety of strategies such as self-assembly,phase separation,electrospinning,chemically crosslinking have been used to construct and mimic the function of the ECM.Based on its designable and dynamic properties,in this thesis,the DNA supramolecular hydrogels were used to construct and mimic the bioresponsive cellular microenvironments,and further to explore its biomedical appliactions containing the neural stem cells differentiation,spinal cord injury repair and tumor immunotherapy.Firstly,through a rational design,the mechanical properties of DNA supramolecular hydrogels could be fine-tuned among from 118 Pa to 1040 Pa by simply exchanging the relative positions of mismatch bases while keeping the same chemical compontens and DNA network topology.Neural stem cells encapsulated within three-dimensional DNA hydrogels could be lasted one week and elicit good biocompatibility.By optimizing the experiment conditions,we demonstrated that the mechanical signals of the three-dimensional DNA matrix could significantly regulate the neural stem cells to differentiate into specialized lineages.Secondly,the rat spinal cord transection model has been established.Various protocols including BBB walking scores,electrophysiological analysis,immunofluorescence and Q-PCR were employed to study the effect of spinal cord injury repair after grafted the compound of DNA hydrogel and neural stem cells.The DNA hydrogel could inhibit the inflammatory and apoptotic cytokines secretion,while promote the neural related genes expression,as well as improve the local damage microenvironment.We demonstrated that the DNA hydrogel could enhance the neurogenesis and promote the locomotor recovery in rats.At last,we successfully constructed an injectable DNA supramolecular hydrogel vaccine(DSHV)system.The antigens and CpG immunostimulants can be immobilized into the DNA hydrogel networks uniformly through electrostatic interactions.Through intraperitoneal or subcutaneous injection,and we demonstrated that the DSHV could recruit and activate the macrophage cells,as well as significantly enhance the immune response in vivo.On tumor bearing mice,the DSHV system significantly suppresses the tumor growth and greatly increases their survival rate.In summary,the function of native cellular microenvironments was constructed and mimicked through the self-assembly.Therefore,the DNA supramolecular hydrogels system could provide a new platform for the biomedical applications in the near future.