Will Shu
Will Wenmiao Shu, Ph.D.
Department of Biomedical Engineering,
University of Strathclyde, Glasgow,
United Kingdom.
Email: will.shu@strath.ac.uk


Will Wenmiao Shu is the Hay Professor in Biomedical Engineering at the University of Strathclyde (Glasgow). He obtained his PhD at the Engineering Department from University of Cambridge, UK. His research interests cover a range of biomedical engineering topics including 3D biofabrication, biosensors, microsystems and their applications for regenerative medicine. He led the research to demonstrate the first bioprinting of human embryonic stem cells (h-ESCs) and human induced pluripotent stem cells (h-iPSCs), paving the way for their applications on animal-free drug testing and 3D printed organs. He held a visiting position at Stanford University. He is an editorial board member for IOP Biofabrication Journal and serves as a board director of the International Society for Biofabrication (ISBF).


Rapid 3D Fabrication of Tubular Organs through Micro Dip Coating

Statement of Purpose: Tubular organs such as the blood vessels, trachea, intestine, biliary and urinary tract are important due to their high demand in surgical procedures. Repopulation of decellularized tissues and organs has been reported to regenerate 3D tissue and can be used as a platform for drug discovery and organ transplantation, but this approach relies on the availability of donated organs so difficult to be scaled up indefinitely. Other fabrication methods of tubular organs present major challenges in tissue engineering including the selection of suitable cells, biomaterials or complex machinery to create the viable, complex tissue constructs. We here present a new, inexpensive, and simple approach to rapid biofabrication that generates cell-laden tubular structures with tuneable micron resolution and the ability to generate multiple layer hydrogel tubular structures.

Methods:  The fabrication method involves micro dip-coating of cell-laden hydrogels covering the surface of a metal bar, into the cross-linking reagents calcium chloride or barium chloride to form hollow tubular structures. This method can be used to form single layers with thickness ranging from 126 to 220?μm or being repeated to form multilayered tubular structures. This fabrication method uses alginate hydrogel as the primary biomaterial and a secondary biomaterial can be added depending on the desired application.

Results: We first demonstrate the feasibility of this method using a range of hydrogel materials (including alginate, gelatin and collagen) to produce highly viable cell-laden biological tubular structures within a few seconds. Mouse dermal embryonic fibroblast cells, human embryonic kidney 293 cells containing a tetracycline-responsive, red fluorescent protein (tHEK cells) were used to verify the concept of the technology. Then, human stem cell derived organoids were used to regenerate a transplantable bile duct. The in-vivo study has shown successful transplantation and the bio-functions of the biofabricated bile duct in mice.

Figure 1. Alginate hydrogel tubular structures fabricated by the new micro dip-coating method. Fabricated single-layer alginate hydrogel tubular structures with various diameters with descending diameters from left to right.

Conclusions: In this study, we have developed a new rapid 3D biofabrication technique for making cell-laden hydrogel tubular structures. Tubular structures from submillimeter, or a few hundred micron range, to greater diameters with an ability to control the thickness of the tube walls have been fabricated using the micro dip-coating technique. This approach may incorporate other biomaterials within alginate hydrogel to help cell biologists to bypass lengthy, complicated and expensive fabrication approaches. The fabrication method is gentle to live cells while maintaining high cell viability within the tubular structures. Human stem cell derived biliary tree has been demonstrated as the first transplantable tubular organs using this new technique. Future work is focused on extending this approach other types of tubular organs such as kidney, lymph vessels, blood vessels, trachea and intestine.

1. Tabriz, A. G., Mills, C. G., Mullins, J. J., Davies, J. A., & Shu, W. Frontiers in bioengineering and biotechnology, (2017): 5.
2. Sampaziotis, F. et al, Nature Medicine, (2017):  Accepted.

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  September 15, 2017