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Polymer and biopolymer derived hydrogels are ideal for replicating human tissue (the extracellular matrix of which is itself a hydrogel).
The fabrication and reproduction of human tissue for medical training and diagnostic purposes is a costly but critical component of quality healthcare. Tubular constructs represent a common type of structure in human anatomy and include renal, vascular, pulmonary, and gastrointestinal tissues. Tubular constructs are geometrically simple, but the fabrication of these structures is still a challenge. Synthetic vessels—composed of biological hydrogels such as collagen—are currently fabricated by casting or rolling a polymeric material around a mandrel, wherein the diameter of this mandrel dictates the size of the lumen. This approach can yield tubular constructs with biological and mechanical properties that are comparable to human blood vessels. However, these approaches are challenged by the cost, as well as the fabrication of small lumen diameters (<1 mm) and arbitrary length tubes (>10 mm).
We recently reported a methodology (in collaboration with the Theberge laboratory at the University of Washington) to fabricate hydrogel-based tubular conduits based on the extrusion of shear-thinning hydrogels from a customizable 3D printed coaxial nozzle.
Different nozzle geometries can be modeled via computer-aided design (CAD) and 3D printed in order to generate tubes or coaxial filaments with different cross-sectional geometries. We were able to fabricate tubes with luminal diameters or wall thicknesses as small as ~ 150 µm. Moreover, these tubes can be functionalized with collagen I to enable cell adhesion, and human umbilical vein endothelial cells (HUVECs) can be cultured on the luminal surfaces of these tubes to yield tubular endothelial monolayers. Our approach enables the rapid fabrication of biofunctional hydrogel conduits which can ultimately be utilized for engineering in vitro models of tubular biological structures, such as blood vessels.
This is just one example that demonstrates how 3D printing is poised to change how we think about research and products of the future. Coaxial nozzles, such as the one we designed, can be rapidly designed and produced via SLA printing within a manner of hours. Without a 3D printer in house, a materials laboratory like ours could not have produced such nozzles without a significant amount of time and investment into machining and assembling individual parts. We hope to make our own designs widely available. Thus, in the spirit of the openness of the 3D printing community, the STEP and STL files of our nozzles are available for those interested in printing their own.
About the Nelson Laboratory: The Nelson laboratory develops stimuli-responsive materials and bio-hybrid materials that are compatible with additive manufacturing (AM) processes. They particularly focus on developing materials for AM that can impact applications in the life sciences.
About the Author:
Alshakim Nelson is an Assistant Professor in the Department of Chemistry at the University of Washington. He received his Ph.D. in organic chemistry from the University of California, Los Angeles in 2004, where he worked with Sir J. Fraser Stoddart on carbohydrate-containing polymers and macrocycles. He was then an NIH postdoctoral fellow at the California Institute of Technology working for Professor Robert Grubbs on olefin metathesis catalysts for the formation of supramolecular ensembles. Dr. Nelson joined IBM Almaden Research Center in 2005 as a Research Staff Member where he focused on the synthesis of nanomaterial building blocks that enabled large area nanomanufacturing via self-assembly. In 2015, Dr. Nelson joined the faculty at the UW, where his research group focuses on the synthesis, characterization, and processing of stimuli-responsive hydrogels for 3D printing. Dr. Nelson has over 40 publications and 11 issued patents. His honors and awards include recognition as an IBM Master Inventor, ACS PMSE Young Investigator, Kavli Foundation Fellow, NSF CAREER award, and 3M Non-Tenured Faculty Award.
Author’s Representative Publications:
Wong, J.; Gong, A. T.; Defnet, P. A.; Meabe, L.; Beauchamp, B.; Sweet, R. M.; Sardon, H.; Cobb, C. L.; Nelson, A. 3D Printing ionogel auxetic frameworks for stretchable sensors. Adv. Mater. Technol. 2019, 4, 1900452.
Shafranek, R. T.; Leger, J. D.; Zhang, S.; Khalil, M.; Gu, X.; Nelson, A. Sticky ends in a self-assembling ABA triblock copolymer: the role of ureas in stimuli-responsive hydrogels. Mol. Sys. Des. Eng. 2019, 4, 91.
Fellin, C. R.; Adelmund, S. M.; Karis, D. G.; Shafranek, R. T.; Ono, R. J.; Martin, C. G.; Johnston, T. G.; DeForest, C. A.; Nelson, A. Tunable temperature- and shear-responsive hydrogels based on poly(alkyl glycidyl ether)s. Polym. Int. 2019, 68, 1238.
Saha, A.; Johnston, T. G.; Shafranek, R. T.; Goodman, C. J.; Zalatan, J. G.; Storti, D. W.; Ganter, M. A.; Nelson, A. Additive manufacturing of catalytically active living materials. ACS Appl. Mater. Interfaces 2018, 10, 13373.
Basu, A.; Saha, A.; Goodman, C.; Shafranek, R. T.; Nelson, A. Catalytically initiated gel-in-gel printing of composite hydrogels. ACS Appl. Mater. Interfaces 2017, 9, 40898.
Karis, D. G.; Ono, R. J.; Zhang, M.; Vora, A.; Storti, D.; Ganter, M. A.; Nelson, A. Cross-linkable multi-stimuli responsive hydrogel inks for direct-write 3D printing. Polym. Chem. 2017, 8, 4199.