Construction And Application Of Hierarchical Multi-functional Hydrogel Based On Polyacrylamide And Poly(n-isopropylacrylamide)

Hydrogels with large amount of water content and good biocompatibility have great application value in the field of biomedicine.The extracellular matrix-like hierarchical network structure also makes hydrogels have natural advantages in simulating living tissues.The three-dimensional network of hydrogels can not only provide good anchor points for cells,but also facilitate biological-related chemical and physical signals transmission which promote cell proliferation and differentiation.However,the inherent weak mechanical properties and the single function of the hydrogel is far from meeting the needs of practical applications.But hydrogel also has the advantage of being highly inclusive.Both the high strength and multifunction can be achieved through nanofillers blending or crosslinking with some other materials.However,the human tissue is very complex,with multiple hierarchical structures and diverse functions.Therefore,the development and application of hierarchical and multi-functional composite hydrogels have received extensive attention in the field of biomedicine.Usually,the preparation of composite hydrogels is divided into two methods.One is to form a binary or ternary hydrogel network by cross-linking different types of polymers with each other,and the second is to fill the hydrogel network with nanofillers such as:gold nanoparticles,graphene,carbon nanotubes,etc..Although the first method may realize the construction of multiple functional hydrogels,it is difficult to meet some high-strength medical application scenarios such as tissue scaffolds due to the limitations of the inherent weak mechanical properties of the polymer chain itself.And the second method can produce hydrogels with high mechanical properties,but the required large amount of fillers may inhibit stimuli-responsive properties of the polymer.Therefore,the preparation of hierarchical and multi-functional composite hydrogels is still difficult.This thesis will explore the preparation and application of hydrogels from two aspects of hierarchical and multi-functional,and prospect its possible development directions and challenges in the field of biomedicine.1.First,we explored the properties and functions of hot materials:gold nanoparticles and carbon nanomaterials.A hybrid nanomaterial of gold nanostars/multiwalled carbon nanotubes?MWCNTs?was synthesized by two-step reduction via the control of several synthetic conditions such as the reducing agent,p H value,concentration and ratio of reagents.The material shows good biocompatibility and high photothermal conversion efficiency,demonstrating its applicability in photothermal therapy.The lack of surfactant in the synthesis process made the hybrid nanomaterial cell-friendly.The MWCNT/gold nanostars hybrid nanomaterial presented 12.4%higher photothermal efficiency than gold nanostars alone and showed a 2.4-fold increase over gold nanospheres based on a heating test under 808 nm laser irradiation.Moreover,the MWCNTs/gold nanostars at low concentration?0.32 nM?exhibited remarkably improved photothermal cancer cellkilling efficacy,which may be attributed to the surface plasmon resonance absorption of the gold nanostars and the combined effects of enhanced coupling between the MWCNTs and gold nanostars.Collectively,these results demonstrate.Then,the prepared gold nanostars were used to chemically modify the surface of polyacrylamide?PAAm?hydrogels for the construction of hierarchical composite hydrogel system with micro-nano scale surfaces?micro-scale PAAm pore structure and nano-scale gold nanostar array?,and explored its effect on bone marrow mesenchyme pro-differentiation of mouse marrow mesenchymal stem cells?MMSCs?.The results show that the high hardness PAAm hydrogel can promote the differentiation of MMSCs into osteoblasts.The surface roughness of PAAm hydrogel modified by gold nanostars has been significantly improved,and the MMSCs can be more easily differentiated into osteoblasts.This hierarchical surface structure constructed by using nanoparticles and pores of hydrogels has potential application value for tissue engineering.2.Two different strategies were developed to prepare stimuli-responsive multifunctional composite hydrogels.First,the?-cyclodextrin??CD?with amphiphilic configuration property was used to demonstrate a facile strategy for the preparation of flexible polyaniline?PANI?-containing conductive hydrogel networks based on preorganized?CD-containing N-isopropylacrylamide??CD-PNIPAM?hydrogels.These materials exhibit high conductivity(0.64 S m^-1),excellent thermoresponsive and self-healing properties.The resulting hybrid hydrogels also contain homogeneous,interconnected macropores and exhibit perfect integration between the host phase??CD-PNIPAM?and the PANI phase,which results in improved mechanical properties and remarkable stability.Second,a simple strategy was demonstrated for achieving controlled drug release and real-time monitoring using an interpenetrating binary network consisting of a graphene aerogel and a poly?N-isopropylacrylamide?hydrogel with incorporated polydopamine nanoparticles?PDA-NPs?.Owing to the good physical properties of graphene and the embedded PDA-NPs,the hybrid hydrogel shows enhanced mechanical properties and good electrical conductivity.In addition,the hybrid hydrogel also shows dual thermo-and near-infrared responsiveness,as revealed by the controlled release of a model drug.In addition,as the hydrogel exhibits detectable changes in resistance during drug release,the drug-release behavior of the hydrogel can be monitor in real time using electrical signals.Moreover,owing to the abundance of catechol groups on the PDA-NPs,the hybrid hydrogel shows good tissue adhesiveness,as demonstrated using in vivo experiments.Thus,the developed hybrid hydrogel exhibits considerable practical applicability for drug delivery and precision medicine.