| Extrusion bioprinting can build bionic tissues and organs due to the precise control of three-dimensional structure,cell distribution,and biological signal,and it has the characteristics of low cost,simple equipment,a wide range of biomaterial inks,and biomimetic printing cell density,indicating that it is an up-and-coming bioprinting technology for industrial applications in drug screening.Biomaterial ink,the key element of bioprinting technology,needs to have both printability and biological activity for constructing shape-like and functionlike tissue.Extrusion type biomaterial ink requires rapid deposition and formation during the printing process,which leads to the lack of extruded biomaterial ink that can be selfsupporting bioprinting.This paper proposes water-soluble hydroxyethyl cellulose(HEC)added as a rheological agent to biomaterial inks for adjusting the performance of bioinks,and developped selfsupporting HEC composite biomaterial inks,HCSG and HECM.On this basis,we bioprinted bionic auricle,liver-like lobule,and breast tumor tissue.Then,printed breast tumor tissues were used to screen 13 isoflavone carbamate derivatives for their anticancer activity.The first part of the paper describes the construction and functional verification of the extrusion based bioprinter.First,we built a mechanical extrusion bioprinter.Then,the printer’s basic performance parameters were determined by testing the temperature control range,printed scaffold size,adaptable nozzle size,printable material,extrusion power,and printing speed.The mechanical extrusion bioprinter has market application potential.The second part of the thesis is the systematic study of the HEC composite biomaterial ink and the bioprinting of the bionic auricle.The effects of different concentrations of HEC on the printability,hydrogel formability,degradation rate,degradability,molecular permeability and biocompatibility of HEC composite biomaterial inks were investigated.Then,we bioprinted centimeter-sized bionic ears with HCSG.The results show that the HEC composite biomaterial inks can be self-supporting bioprinted without affecting hydrogel crosslinking.HCSG has high molecular permeability and certain universal cell compatibility,and can be constructed tissues with complex geometric structure,indicating it has great potention in bioprinting application.The third part of the paper describes the performance of HECM and the bioprinting of hepatic lobules.First,we prepared HECM with different concentrations.Then,the hydrogel formability,printability and biological activity of HECM were investigated.Using with primary hepatocytes encapsulated in HECM,we bioprinted hepatic lobule-like tissue,and tested its albumin synthesis function and metabolithe dLECM was fabricated and characterized,enzyme activity.The results show that HECM can be extruded to print high-fidelity 3D scaffolds,the biological activity is liver-specific,and the printed hepatic lobule-like tissue have good liver biological functions,which indicates that HECM has a good application prospect in liver tissue engineering.The fourth part of the thesis describes the construction of breast tumor tissue and application for compounds anti-tumor activity screening.Firstly,the biological activity on MCF7 cells of HCSG were investigated.Secondly,we bioprinted MCF7 cells encapsulated in HCSG for constructing the breast tumor microsphere model,which was compared with other models on the cell viability and drug effects.Finally,based on the bioprinted breast tumor microsphere model,the anti-tumor activities of 13 isoflavone carbamate derivatives were tested and compared.The results show that the biological activity of HCSG is similar to Geltrex on MCF7 cells and the bioprinted breast tumor tissue mimics the tumor microenvironment.Comparing with the 2D culture model,the drug sensitivity of bioprinted breast tumor tissue is low,and the drug structure affects the drug sensitivity. |
PDF Full Text Request