| Nowadays,the development of science and technology is speeding up the cross and integration of high and new technologies such as biomedicine,intelligent materials,additive manufacturing and information technology.Especially in our society where the elderly group is more and more large,the problems of multiple diseases co occurrence and chronic disease management have become increasingly prominent.The problems such as taking multiple drugs at the same time and taking the same drug several times every day not only seriously affect the daily life of patients,but also bring many difficulties to the management of drug treatment.The development of a new generation of drug carriers with stress response and intelligent controlled release function has important research value and significant economic and social comprehensive benefits for improving the quality of life of hundreds of millions of patients,facilitating drug treatment management and meeting the needs of treatment schemes.As a new drug controlled release carrier,intelligent hydrogel has multiple environmental response ability,self driving deformation ability,low cytotoxicity and excellent hemolysis.It has been widely used in biological tissue engineering scaffolds,artificial muscles,wound hemostasis and anti inflammatory dressings and electronic skin sensors.However,the smart response self driving hydrogels with good biocompatibility can not meet the actual needs of medical drugs,and can not prepare complex shapes.Moreover,the release effect can not be controlled repeatedly,repeatedly and accurately in the incentive environment.Therefore,the design and preparation of smart drug loaded supramolecular materials with excellent biocompatibility,intelligent response characteristics and drug loading function has become an urgent problem to be solved.Intelligent hydrogel has many kinds and different properties.Among them,intelligent biomedical supramolecular materials can realize "perception","feedback","self driving","shape memory" and "biocompatibility",and can self drive and deform in response to the changes of environmental humidity,temperature,electromagnetic,p H and optical intensity,so as to achieve the desired effect.In the past,most of the traditional drug capsules were made of gelatin,cellulose,polysaccharides and other materials.The drug was gradually released through dissolution or pore structure.Due to its hard quality,large volume and poor release ability,it could not be well solved in nasal feeding and multi drug administration.Bionic intelligent supramolecular hydrogels inspired by biologically intelligent deformable structures provide the possibility to solve these problems,and have broad application prospects in long narrow nasal feeding pipeline devices and biocompatible drug controlled release.Based on the two hydrogel systems of Polyacrylamide / chitosan(PAAm/CS-Odex)and sodium alginate / methacrylic acid two methylamino ethyl ester(Alg/PDMAEMA),a double-layer hydrogel structure with bionic anisotropy was designed based on the self driving principle of wild wheat seed.By introducing different functional chemical groups,hydrogel can be given shape memory,temperature response,ion response and other intelligent capabilities.On the one hand,by adjusting the concentration of N,N ’-methylene bis acrylamide,the cross-linking density of PAAm/CS-Odex bilayer structure is controlled,and a shape memory bionic double-layer structure hydrogel with good swelling self driving property is prepared by using the mold.On the other hand,by adjusting the concentration of Ca2+ ions,Alg/Alg-PDMAEMA hydrogels with gradient density are obtained.The temperature response characteristics of PDMAEMA based double layer interpenetrating network hydrogel are temperature sensitive,and the self-propelled performance of the two layers is tested in different ionic solution environments by the ion response characteristics of the bilayer structure.Finally,we evaluated the microstructures,mechanical properties and biocompatibility of biomimetic hydrogels,and further verified the feasibility of bionic intelligent hydrogel system in biomedical applications.It provided a research basis for obtaining new drug carrier materials with low cytotoxicity,low hemolysis,good mechanical properties and intelligent response characteristics.The research contents and main conclusions of this paper are as follows:(1)based on the PAAm/CS-Odex hydrogel material system,the bilayer structure material was prepared by the mold forming method.By adjusting the content of N,N ’-methylene bis acrylamide,different bi layer structures were constructed,and the bionic intelligent water gel with different network density was obtained.The results showed that with the increase of the content of N,N ’-methylene bis acrylamide,the size of bionic PAAm/CS-Odex type intelligent hydrogel decreased gradually,and the crosslinking density,mechanical strength and strain value increased significantly.The high bonding strength between the two layers of intelligent hydrogel provides a structural foundation for stress expansion and shape memory bending deformation;the different pore density between layers forms swelling anisotropy and generates driving force;with the increase of N,N ’-methylene bis acrylamide content,the expansion bending degree increases.(2)based on the Alg/Alg-PDMAEMA material system,a thermal responsive double-layer hydrogel with biomimetic structure and self growth was prepared.Through the coordination of the alginate chain with Ca2+ diffused in gelatin,the first layer of ionic strength responsive alginate film was prepared.Then,second layers of temperature responsive Alg-PDMAEMA films were prepared by diffusion induced gelation and DMAEMA polymerization at the same time.The results show that the Alg/Alg-PDMAEMA hydrogels with double gradient structure can undergo complex deformation,and spontaneously form a cigar shaped cylinder from the plane triangle through the fine structure design.The bionic planar hydrogel blades can be self driven curled,and the biomimetic hydrogel flowers can produce complex self driving actions such as closure and opening after the change of ambient temperature and ions.In the pre-designed mode,the complex shape conversion from two-dimensional to three-dimensional can be realized by gradually adjusting the temperature and ionic strength,and it is expected to achieve more complex driving behavior through this strategy.(3)in order to verify the biomedical application prospect of the intelligent controlled release bionic hydrogel system,this study simulated the internal environment of the organism,extracted and sterilize the hydrogel through the extraction method,conducted cytotoxicity test by CCK8 method,and tested the biocompatibility of the different proportion of hydrogels.The results showed that Alg/Alg-PDMAEMA hydrogel had acceptable cytotoxicity and good biocompatibility.After introducing PDMAEMA,it was confirmed that the cytotoxicity of the double network interpenetrating polymer hydrogel did not change significantly,and it also verified that PDMAEMA had good cytocompatibility.(4)haemolysis test was performed on four groups of hydrogels of 1h+2h,2h+2h,1h+1h and 2h+1h respectively based on rabbit erythrocytes.Through the absorbance test of the extraction solution and the red blood cell suspension after contact,then determine whether the red blood cell broken and dissolved reaction.The study showed that the hemolytic percentage of the four groups of hydrogels was between 2.57-3.88%,which confirmed that the Alg/Alg-PDMAEMA hydrogel material system had good blood compatibility,which provided a material basis for further exploring the application direction of intravascular injectable drugs and wound dressing. |
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