Study On Improvement Of Mechanical Properties And Biocompatibility Of 3D Printed ODMA-GelMA Hydrogel By Layer Self-assembly Method

In order to realize the replacement of tissues and organs in the treatment of cardiovascular diseases,it is imperative to find a suitable bio-ink for three-dimensional construction to print the replacement of tissues and organs.GelMA hydrogel,as a kind of biomaterial with good biocompatibility and cell activity,has been widely used in bio-ink printing.However,the mechanical properties of the bio-ink printing are not excellent,so it is necessary to improve the mechanical properties and further improve its biocompatibility in order to be used for the printing of artificial blood vessel materials.By inserting ODMA into GelMA,the ODMA-GelMA hydrogel can be made more ductility and elasticity.The purpose of this paper is to improve the mechanical properties and biocompatibility of ODMA-GelMA hydrogel,so that it can meet the performance requirements as a substitute for artificial blood vessels.In the experiment,a 3D printer was used to print the ODMA-GelMA hydrogel,and the artificial vessel structure with hollow tube was printed,and adopt layer-by-layer self-assembly method to construct（RSF/CHI）_nmultilayer composite film on the surface of ODMA-GelMA hydrogel.The hydrogel after assembling the multilayer composite film was characterized by SEM,and its stress and strain,Young’s modulus and swelling rate were measured,and the mechanical performance parameters of the biomaterial were obtained.Next,He La cells were used to test cell compatibility,CCK-8 reagent and fluorescent double staining reagent were used to test the survival of the cells in the hydrogel,and then the hydrogel extract was injected into the tail vein of the mouse and the mouse was dissected.The tissues were prepared into slices to observe the biological activity of the hydrogel in the body.The hydrogel extract is used as the source of environmental contact for the model organism of Caenorhabditis elegans,and analyze the body length,survival rate and movement speed of the nematode through its entire survival period,and obtain the long-term toxic effect parameters of the hydrogel material on the organism.By studying the mechanical properties,cell compatibility,blood compatibility,acute and long-term toxicity effects of ODMA-GelMA hydrogels assembled（RSF/CHI）_nmultilayer composite membranes,the results show that:（1）Assembly（RSF/CHI）_nmultilayer composite film can improve the mechanical properties of hydrogels,so that the compressive performance of hydrogels,toughness and strength are improved,and the assembly can be obtained through the observation and analysis of the cross-section after the（RSF/CHI）_nmultilayer composite membrane,the pore size of the hydrogel becomes tighter and the pore size becomes smaller,which is why its performance has improved.（2）Cell compatibility and blood hemocompatibility:The cell proliferation was detected through the CCK-8 experiment and the fluorescence double staining experiment.The results showed that the hydrogel extract was not toxic to the cell growth,and the cell proliferation was good.And as the number of assembled layers increases,the number of cell proliferation increases.In the experiment to detect the hemolysis rate of composite hydrogel,the hemolysis rate of the hydrogel extract of the assembled（RSF/CHI）_ncomposite membrane is lower than the hemolysis rate of normal non-hemolytic materials,so it is satisfied as Hemolysis conditions of artificial blood vessel materials.（3）Acute toxicity in vivo:The acute in vivo toxicity of the material was detected by injecting the hydrogel extract into the tail vein of mice.The results showed that no obvious inflammatory reaction was observed in the tissue sections of the heart,liver,spleen,lung,kidney and brain 7 days after the injection of the extract.No significant toxicity of the composite hydrogel material was detected in mice and it affected the normal tissues and organs of mice,indicating good biocompatibility in vivo.（4）Long-term toxic effects in vivo:There were no significant differences in life span,body length and swimming rate of nematodes after adding hydrogel extract compared with those without.However,the progeny number of C.elegans decreased significantly,suggesting that we should not ignore the long-term toxicity of C.elegans.Through the modification analysis of ODMA-GelMA hydrogel,the ODMA-GelMA hydrogel with（RSF/CHI）₁₀multilayer composite film was obtained.The comprehensive evaluation of the ODMA-GelMA hydrogel was better improved from the aspects of mechanical properties,biocompatibility and economy,which can be used as 3D printing material for artificial blood vessels.