Fabrication Of Cell-Integrated Flexible Film Substrates And Their Biomedical Applications

As an important branch of material science,thin film material is experiencing a rapid evolution in recent decades.Up to date,various film materials have been developed and have found wide application prospects in the field of sensing,electrical devices,optical devices,drug release,cell culture and so on.Among them,flexible thin film materials are receiving extensive attention and research for their excellent flexibility and adaptability.Two-dimensional(2D)cell culture occupies an important position in the basic research of cell biology and drug test,owing to the advantages of low cost and easy operation.To enable normal proliferation and maintain structure and function of cells in vitro,the key is providing a microenvironment that similar to in vivo one,including oxygen,carbon dioxide,nutrient supply and temperature,etc.Based on this cell functional layer,it is conducive to carrying out drug screening,toxicity testing,viral or microbial studies and even tissue engineering,exploring microscopic biological mechanisms and providing a research platform for practical clinical applications.However,most existing2 D cell culture is limited to the solid substrates where cells can only extend on the plane,which restricts the interaction between cells and the substrate.In addition,the current substrates are usually lack of elaborate design on surface morphology,and thus unable to well simulate the microenvironment in vivo.More importantly,the biomedical values of these cell-integrated flexible films have been seldom explored and extended.Therefore,the development of novel flexible substrates for cell integration has a milestone significance for promoting the development of biology,medicine,pharmacy and other disciplines.In this paper,we will conduct cell culture based on flexible thin film materials,study the interaction between materials and cells,and apply it to construct biohybrid robots,organ-on-a-chip,medical patches and other biomedical fields.The main research contents are as follows:(1)Based on biocompatible methacrylated gelatin(GelMA)hydrogel scaffold,a paralleloriented carbon nanotube(CNT)layer,an anisotropic structure layer and a non-close-packed structural color layer were successively integrated with the scaffold to obtain a conductive structural color hydrogel substrate for constructing bio-hybrid robots.Based on template method,parallel CNT-integrated GelMA microneedle(MN)patches with cytokine encapsulation and MXene-integrated MN patches loaded with adenosine were fabricated,respectively.(2)When applied for cell culture,the influence of micro/nano structure distributed on the surface of the thin film materials on cell adhesion,proliferation,differentiation and orientation was investigated.In addition,the driven efficiency of cardiomyocytes on flexible substrates,which could convert weak cell behavior into observable displacement change,was also explored.By utilizing the structural color layer as an optical indicator,parameters of the composite system such as the movement ability could be visually monitored.(3)Based on the integration of cardiomyocyte-driven conductive structural color hydrogel substrates and advanced microfluidic technology,a visualized heart-on-a-chip system was developed.With the pumping of drugs such as isoproterenol solution,the movement speed of the biohybrid robot was observed and recorded to realize the rapid evaluation of the drug effect.In addition,a disease model was constructed to observe the therapeutic effect of drugs on the disease for drug screening.Except for the movement speed of biohybrid robots,the structural color layer could also reflect the viability and contraction frequency of cardiomyocytes by optical signals,thus ensuring the visualization for drug screening.(4)Based on flexible GelMA hydrogel MN array patch,induced pluripotent stem cells(i PSCs)were successfully induced into rhythmically beating cardiomyocytes.When applied for treating myocardial infarction models on mouse,the cardiomyocyte-integrated flexible MN array patch loaded with cytokines showed effect on inhibiting left ventricular wall thinning and maintaining the cardiac function.(5)Based on MXene-integrated MN patches with adenosine encapsulation,the release of adenosine could be accelerated upon NIR irradiation,attributed to the excellent photothermal conversion capacity of MXene.When applied for treating animal models,it was demonstrated that the composite patches could promote angiogenesis and thus facilitate the repair process of wounds.