Experimental Study Of Mechanically Enhanced Light Crosslinkable Gelatin-hyaluronic Acid Composite Hydrogel For 3D Bioprinting

Objective: To investigate the problems related to the poor mechanical properties and degradability of common hydrogels.In this study,Gel MA-HAMA composite hydrogels were prepared by using Gelatin Methactyloyl(Gel MA)and Hyaluronic Acid Methacryloyl(HAMA)hydrogels to investigate the differences of their physicochemical properties and the feasibility of their application in 3D bioprinting.Method: Part I: The composite hydrogels with different mass percent concentrations and ratios were prepared and characterized physicochemically,including morphological and structural observations,swelling properties,degradation properties,rheological properties and compression properties,to investigate the differences in physicochemical properties between single network hydrogels and composite hydrogels.Part II: Selecting suitable groups of composite hydrogels for 3D bioprinting and biocompatibility assessment based on the experimental structures in Part I.The study includes printing of hydrogel scaffolds with/without cells,culturing of cells on the surface of hydrogels,culturing of cell-laden hydrogel scaffolds in vitro,and subcutaneous implantation of hydrogel scaffolds without cells in the back of SD rats to investigate the printing,molding performance,and in vivo and in vitro biocompatibility of composite hydrogels.Result: Compared with the single network hydrogel,the composite hydrogel has no significant difference in morphological structure,the in vitro degradation rate is significantly delayed,the mechanical properties are significantly enhanced,and the mechanical properties can be adjusted by changing the concentration and ratio of components.The composite hydrogel has the same shear thinning characteristics as Gel MA hydrogel,which can meet the needs of extruded 3D bioprinting.It’s swelling performance is lower than single network hydrogels.The composite hydrogel can be deposited and shaped by the extruded 3D bioprinter with smooth printing process and stable printing scaffold.Its biocompatibility is similar to that of Gel MA hydrogel,which does not show obvious cytotoxicity and can provide a good living environment for cells.Conclusion: Gel MA hydrogel is one of the commonly used bioactive materials in the field of tissue engineering,and its biosafety has been fully proved.The biocompatibility of Gel MA-HAMA composite hydrogel is not significantly different from Gel MA hydrogel with significantly enhanced mechanical properties.Moreover,Gel MA-HAMA composite hydrogel can be well used for printing hydrogel scaffolds by 3D bioprinters with controllable printing parameters and easy cross-linking curing method,which is an ideal material for 3D bioprinting hydrogel.