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Coaxial nozzle-assisted 3D bioprinting with built-in microchannels for nutrients delivery

Significance Statement

Bioprinting is an exciting new technique that has been applied to the field of tissue engineering. Because cells require in vitro culturing prior to implantation, the fabricated 3D hydrogel structures must be adequately perfused to allow delivery of growth factors, oxygen, and other nutrients. Thus, the integration of a vascular network as occurs in thick tissues or organs is necessary and the most critical challenge in the successful application of bioprinting.

This study offers a novel 3D bioprinting method based on hollow calcium alginate filaments by using a coaxial nozzle, in which high strength cell-laden hydrogel 3D structures with built-in microchannels can be fabricated by controlling the crosslinking time to realize fusion of adjacent hollow filaments. With nutrition, cells are able to live longer, which allows easy fabrication of larger-scale organs with built-in microchannels as vascular network. This method can also be used in fabrication of hydrogel-based microfluidic devices, cell-based biosensor, and drug screening chips. 

About The Author

Yong He obtained his B.E. in engineering mechanics, at the China University of Mining and Technology in 2001. He obtained his Ph.D degree in mechanical engineering at the Zhejiang University in 2008. He is currently an associate professor at Zhejiang University, College of Mechanical Engineering. Also he is the deputy director of Key Lab of 3D Printing Process and Equipment of Zhejiang Province. His research is focused on the cell printing, development of organs on chips and microfluidic analytical devices. Now he has published above 30 papers and authorized above 30 patents. 

About The Author

Qing Gao receieved his B.E. in School of Mechanical and  Automotive Engineering at Hefei University of Technology in 2012. He is currently a doctoral student in the College of Mechanical Engineering at Zhejiang University. His research focuses on bioprinting and biofabrication. 

About The Author

An Liu receieved his M.S. in School of Medicine at Wuhan University in 2013. He is currently a doctoral student in School of Medicine at Zhejiang University. His research focuses on bone defect repair and regeneration.  

About The Author

Dr Liang Ma received his Ph.D from mechanical engineering Department, University of Washington in Mar 2012. Then He jointed Zhejiang California NanoSystems Institute, Zhejiang University as research associate in Sep 2012. Currently Dr Liang focuses on the fabrication of novel tissue model systems with 3D cell printing. His researches including three aspects: In vitro glioblastoma multiforme (GBM) invasion model; 3D follicular model for in vitro maturation; 3D liver model for HBV infectious.   

 

Journal Reference

Biomaterials. 2015:203-15.

Gao Q1, He Y2, Fu JZ1, Liu A3, Ma L4.

Show Affiliations
  1. The State Key Lab of Fluid Power Transmission and Control, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China; Key Laboratory of3D Printing Process and Equipment of Zhejiang Province, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China.
  2. The State Key Lab of Fluid Power Transmission and Control, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China; Key Laboratory of3D Printing Process and Equipment of Zhejiang Province, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: [email protected]
  3. Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
  4. Zhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou 310058, China.

Abstract

This study offers a novel 3D bioprinting method based on hollow calcium alginate filaments by using a coaxial nozzle, in which high strength cell-laden hydrogel 3D structures with built-in microchannels can be fabricated by controlling the crosslinking time to realize fusion of adjacent hollow filaments. A 3D bioprinting system with a Z-shape platform was used to realize layer-by-layer fabrication of cell-laden hydrogel structures. Curving, straight, stretched or fractured filaments can be formed by changes to the filament extrusion speed or the platform movement speed. To print a 3D structure, we first adjusted the concentration and flow rate of the sodium alginate and calcium chloride solution in the crosslinking process to get partially crosslinked filaments. Next, a motorized XY stages with the coaxial nozzle attached was used to control adjacent hollow filament deposition in the precise location for fusion. Then the Z stage attached with a Z-shape platform moved down sequentially to print layers of structure. And the printing process always kept the top two layers fusing and the below layers solidifying. Finally, the Z stage moved down to keep the printed structure immersed in the CaCl2 solution for complete crosslinking. The mechanical properties of the resulting fused structures were investigated. High-strength structures can be formed using higher concentrations of sodium alginate solution with smaller distance between adjacent hollow filaments. In addition, cell viability of this method was investigated, and the findings show that the viability of L929 mouse fibroblasts in the hollow constructs was higher than that in alginate structures without built-in microchannels. Compared with other bioprinting methods, this study is an important technique to allow easy fabrication of lager-scale organs with built-in microchannels.

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Coaxial nozzle-assisted 3D bioprinting with built-in microchannels for nutrients delivery. Global Medical Discovery