Studies On Novel Biomedical Device Based On Nucleoside & Nucleic Acid Hydrogels

Hydrogels are multi-component system composed of 3D crosslinking network and water.The crosslinking network contains a large number of hydrophilic groups.Due to the characteristics of high water content,extracellular matrix-like structure,and also biocompatibility,hydrogels have been widely used in biomedical fields such as drug delivery,tissue engineering,cell culture,and bioadhesion in recent years.Much research has also been focusing on the use of hydrogels in the development of soft robots and smart soft materials.In the field of DNA nanotechnology,DNA is no longer used as a carrier of genetic information,but as a building material for precise assembly of nanomaterials and nanodevices.This benefits from the programmability and the ease of chemical modification of DNA.With the rapid development of DNA synthesis and modification technologies,DNA macroscopic materials has also been developed,especially the responsive DNA hydrogel.However,the existing smart hydrogels,including DNA hydrogels,are relatively plain in structure and can only respond to a single signal,which is designed in advance.Developing conditionally responsive smart hydrogels that can perform more complex functions has great significance for the development of soft materials and soft robots.In this thesis,based on dynamic DNA nanotechnology,we propose a conditionally responsive smart hydrogel swelling system that can integrate and reconnect signals based on the environmental stimuli and respond to specific signal pathways.As a component of deoxyribonucleic acid(DNA),nucleosides have biochemical properties similar to DNA.Nucleosides and their derivatives have abundant functional groups that enable them to bind to each other through non-covalent interactions.Compared to biomolecules such as proteins,nucleic acids and lipids,nucleosides have the advantages of small molecular weight,good stability,and low cost,they are ideal building blocks for supramolecular self-assembly materials.Based on these advantages of nucleosides,we use nucleoside-metal coordination to prepare three kind of injectable supramolecular hydrogels in a fast,simple,and low-cost way,and according to their characteristics,they are applied to promote the healing of a deep second-degree scald on the mouse model and the development of a flexible biosensor.The details of each section are as follows:(1)Injectable hydrogels are increasingly being used as scaffolds for in situ tissue engineering and wound healing.Most of these injectable hydrogels are made from polymers,and there are fewer examples of such soft materials made via self-assembly of low-molecular weight gelators.We report the room-temperature synthesis of a functional hydrogel formed by mixing cytidine(C)with 0.5 equiv each of B(OH)₃ and Ag NO₃.The structural basis for this supramolecular hydrogel(C2·Ag⁺)involves orthogonal formation of cytidine borate diesters(C-B-C)and Ag+stabilized C-C base pairs,namely,the C·Ag⁺·C dimer.The C2·Ag⁺hydrogels,which can have high water content(at least 99.6%),are stable(no degradation after 1 year in the light),stimuli-responsive,and self-supporting,with elastic moduli of up to 10⁴ Pa.Incorporation of Ag⁺ions into the gel matrix endows the C2·Ag⁺hydrogel with significant antibacterial capability.Importantly,the rapid switching between the sol and gel states for this supramolecular hydrogel,as a response to shear stress,enables 3D printing of a flexible medical patch made from the C2·Ag⁺hydrogel.The C2·Ag⁺hydrogel was used to promote the closure of burn wounds in a mouse model.(2)Conductive hydrogels are important parameters for preparing flexible electronic devices.However,the existing strategies of conductive hydrogel fabrication require chemical modification the crosslinking monomer,or synthesis of the electrical conducting materials,which are entrapped within the gel matrix.These conventional strategies are not only complicated,but also time-consuming and costly.Besides,the the hydrophobic nature of conductive polymers making processing difficult.In the third chapter,we proposed a method to prepare silver nanowire(Ag NWs)networks by in-situ photoreduction within a low molecular weight supramolecular hydrogel,which result in a conductive supramolecular hydrogel/silver nanowire network complex.We investigated the electrical properties of the conductive hydrogel,and applied it as a flexible biosensor for glucose sensing by loading glucose oxidase in the gel.Compared with the conventional fabrication methods of conductive hydrogel,the approach we proposed has the advantages of low cost and easy to process.The conductive hydrogel has a shear thinning property,which makes it a promising conducing material being applied to the patterning fabrication of soft and flexible electronic devices.(3)Conducting hydrogels provide great potential for creating designer shapemorphing architectures for biomedical applications owing to their unique solid–liquid interface and ease of processability.Here,a novel nanofibrous hydrogel with significant enzyme-like activity that can be used as“ink”to print flexible electrochemical devices is developed.The nanofibrous hydrogel is self-assembled from guanosine(G)and KB(OH)₄ with simultaneous incorporation of hemin into the G-quartet scaffold,giving rise to significant enzyme-like activity.The rapid switching between the sol and gel states responsive to shear stress enables free-form fabrication of different patterns.Furthermore,the replication of the G-quartet wires into a conductive matrix by in situ catalytic deposition of polyaniline on nanofibers is demonstrated,which can be directly printed into a flexible electrochemical electrode.By loading glucose oxidase into this novel hydrogel,a flexible glucose biosensor is developed.This study sheds new light on developing artificial enzymes with new functionalities and on fabrication of flexible bioelectronics.(4)Cell proliferation,differentiation,and apoptosis are regulated on the molecular level by chemical reaction network,which plays a vital role in life activities.Developing smart soft materials with embedded“conditional chemical reaction network”is of great significance to the development of biomimetic soft robots.In this work,we propose a general p H-controlled strand displacement method.Without additional design of the target sequence,the rate of strand displacement reaction can be tuned in three p H windows,spanning two orders of magnitude.We then built a p H-responsive multilayer DNA circuits based on this method.Finally,by inserting a p H switch on the crosslinking site of a DNA microgel and combining a multilayer DNA circuit,we propose a conditional responsive smart micro-gel swelling system that can respond to specific signal pathways according to environmental stimuli.The smart hydrogel is pre-programmed with a variety of signal pathways,and specific signal pathways would be selectively executed according to external conditions,eventually give a feedback of swelling.