Template-Enabled Biofabrication of Thick 3D Tissues with Patterned Perfusable Macrochannels

Elham Davoodi; Hossein Montazerian; Masoud Zhianmanesh; Reza Abbasgholizadeh; Reihaneh Haghniaz; Avijit Baidya; Homeyra Pourmohammadali; Nasim Annabi; Paul S Weiss; Ehsan Toyserkani; Ali Khademhosseini

doi:10.1002/adhm.202102123

Template-Enabled Biofabrication of Thick 3D Tissues with Patterned Perfusable Macrochannels

Adv Healthc Mater. 2022 Apr;11(7):e2102123. doi: 10.1002/adhm.202102123. Epub 2022 Jan 12.

Authors

Elham Davoodi^{1

2

3

4}, Hossein Montazerian^{2

3

4}, Masoud Zhianmanesh⁵, Reza Abbasgholizadeh⁴, Reihaneh Haghniaz⁴, Avijit Baidya⁶, Homeyra Pourmohammadali⁷, Nasim Annabi⁶, Paul S Weiss^{2

3

8

9}, Ehsan Toyserkani¹, Ali Khademhosseini⁴

Affiliations

¹ Multi-Scale Additive Manufacturing Laboratory, Mechanical and Mechatronics Engineering Department, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
² Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
³ California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁴ Terasaki Institute for Biomedical Innovation, Los Angeles, CA, 90024, USA.
⁵ School of Biomedical Engineering, University of Sydney, Sydney, New South Wales, 2006, Australia.
⁶ Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁷ Department of System Design Engineering, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
⁸ Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁹ Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

Abstract

Interconnected pathways in 3D bioartificial organs are essential to retaining cell activity in thick functional 3D tissues. 3D bioprinting methods have been widely explored in biofabrication of functionally patterned tissues; however, these methods are costly and confined to thin tissue layers due to poor control of low-viscosity bioinks. Here, cell-laden hydrogels that could be precisely patterned via water-soluble gelatin templates are constructed by economical extrusion 3D printed plastic templates. Tortuous co-continuous plastic networks, designed based on triply periodic minimal surfaces (TPMS), serve as a sacrificial pattern to shape the secondary sacrificial gelatin templates. These templates are eventually used to form cell-encapsulated gelatin methacryloyl (GelMA) hydrogel scaffolds patterned with the complex interconnected pathways. The proposed fabrication process is compatible with photo-crosslinkable hydrogels wherein prepolymer casting enables incorporation of high cell populations with high viability. The cell-laden hydrogel constructs are characterized by robust mechanical behavior. In vivo studies demonstrate a superior cell ingrowth into the highly permeable constructs compared to the bulk hydrogels. Perfusable complex interconnected networks within cell-encapsulated hydrogels may assist in engineering thick and functional tissue constructs through the permeable internal channels for efficient cellular activities in vivo.

Keywords: 3D bioprinting; additive manufacturing; biofabrication; cell-laden hydrogels; gelatin methacryloyl.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Bioprinting* / methods
Gelatin*
Hydrogels
Methacrylates
Plastics
Printing, Three-Dimensional
Tissue Engineering / methods
Tissue Scaffolds

Substances

Hydrogels
Methacrylates
Plastics
gelatin methacryloyl
Gelatin

Grants and funding

R01 AR073135/AR/NIAMS NIH HHS/United States