Fabrication Of Hollow Microfiber Via 3D Printing-Assisted Coaxial Microfluidic Chips And Its Research As Biomimetic Blood Capillary

Blood capillaries are widely distributed in the human body and have important physiological functions such as blood transport,substance exchange and immune regulation.The structure and function simulation of blood capillaries in vitro play an important role in understanding the function of blood capillaries and constructing artificial tissues and organs.At present,in the field of tissue engineering,hollow hydrogel fiber is recognized to be more suitable for simulating natural blood capillaries.Among preparation methods of hollow hydrogel fiber,coaxial microfluidic technology is a common method.However,the traditional lithography-based fabrication method has some disadvantages such as long time and complex operation,and it is not conducive to the preparation of coaxial microfluidic chips with three-dimensional structure.Based on this,a coaxial microfluidic chip manufacturing strategy based on 3D printing is proposed in this paper.The coaxial microfluidic chip is fabricated by a template of 3D-printed hydrogel.Furthermore,hollow hydrogel fibers were prepared by the rapid ion cross-linking reaction of sodium alginate with calcium ion,barium ion and so on.On this basis,the physicochemical and cytological properties of hollow hydrogel fibers as biomimetic blood capillaries were studied systematically.The main contents and conclusions of this work are as follows:(1)3D printing-assisted preparation of coaxial microfluidic chip: the template of microfluidic chip is prepared by the using of gelatin hydrogel as 3D printing ink and the controlling of the printing extrusion pressure,and then the template is processed by the curing of PDMS at high temperature.Finally,the coaxial microfluidic chip is obtained.The experimental results show that the coaxial microfluidic chip has obvious height difference between the inner and outer channel,which can meet the needs of coaxial flow.Moreover,the channel size of the coaxial microfluidic chip can be adjusted by controlling the parameters of3 D printing.(2)Preparation and characterization of hollow hydrogel fiber: low concentration calcium chloride or barium chloride solution is introduced into the inner channel of the coaxial microfluidic chip.Sodium alginate solution or the mixed solution of sodium alginate and methacryloyl gelatin is introduced into the outer channel.Hollow hydrogel fiber is obtained by the ion cross-linking reaction of alginate with calcium ion or barium ion.The experimental results show that hollow hydrogel fibers with multiple structures can be prepared by coaxial microfluidic chips with different structures,and their inner and outer diameters can be adjusted by controlling the flow rate of the solution in the channel.In addition,the hollow hydrogel fiber with double shell structure can be obtained by further post-processing.And the second shell thickness of the double-shell hollow hydrogel fiber can be controlled by the illumination time and the soaking time of the fiber in the monomer solution.(3)The characterization of hollow hydrogel fiber as biomimetic blood capillary: firstly,the physicochemical properties of hollow hydrogel fiber are characterized systematically.The results show that the hollow hydrogel fiber which can occur obvious capillarity has good material transport ability.And it has blood compatibility in accordance with the national standard of hemolysis test,good semi-permeability which can meet the exchange of small molecular substances and prevent the leakage of red blood cells and good mechanical properties.Secondly,the cell experiments show that endothelial cells can grow and proliferate well and express characteristic CD31 protein in the wall of hollow hydrogel fiber.On this basis,the barrier function of hollow hydrogel fiber with or without endothelial cells is further studied on substances of different sizes.The results show that the hollow hydrogel fiber prepared in this work allow the entry of small molecules and prevent the entry of macromolecules and cellular substances,which is a similar to the barrier function of natural blood capillaries.In a word,the coaxial microfluidic chip assisted by 3D printing is prepared,and the hollow hydrogel fiber is further prepared by microfluidic chip.The feasibility of hollow hydrogel fiber as blood capillary is studied systematically,which provides a new method and idea for the construction and functional simulation of biomimetic blood capillaries in vitro.