Utilizing bioprinting to engineer spatially organized tissues from the bottom-up

Abstract

In response to the growing demand for organ substitutes, tissue engineering has evolved significantly. However, it is still challenging to create functional tissues and organs. Tissue engineering from the 'bottom-up' is promising on solving this problem due to its ability to construct tissues with physiological complexity. The workflow of this strategy involves two key steps: the creation of building blocks, and the subsequent assembly. There are many techniques developed for the two pivotal steps. Notably, bioprinting is versatile among these techniques and has been widely used in research. With its high level of automation, bioprinting has great capacity in engineering tissues with precision and holds promise to construct multi-material tissues. In this review, we summarize the techniques applied in fabrication and assembly of building blocks. We elaborate mechanisms and applications of bioprinting, particularly in the 'bottom-up' strategy. We state our perspectives on future trends of bottom-up tissue engineering, hoping to provide useful reference for researchers in this field.

Keywords: Assembly; Bioprinting; Bottom-up; Building blocks; Tissue engineering.

Fig. 1

Workflow of bottom-up tissue engineering. In bottom-up tissue engineering, biomaterials, cells and biomolecules (to support the survival of cells, direct the differentiation or other functions) (A) are the basic components to fabricate building blocks. The structure and size of building blocks depends on its application and fabrication method (B), while cell spheroids, organoids, cell fibers or microgels of specific shapes (C) are commonly used. Then the building blocks are assembled through self-assembly, manual assembly or bioprinting (D) to an organized artificial tissue (E)

Fig. 2

Mimic fundamental units of living tissues. A Haversian bone–mimicking bioceramic scaffolds (from Zhang M, Lin R, Wang X, et al. Sci Adv. 2020;6(12), reproduced under the terms of Creative Commons Attribution NonCommercial License 4.0). B Microscale hexagonal model mimicking liver lobules (Reproduced with permission, Ma X, Qu X, Zhu W, et al. Proc Natl Acad Sci. 2016;113(8):2206–2211). C Core–shell bioprinted liver sinusoid-like model (from Taymour R, Chicaiza-Cabezas NA, Gelinsky M, Lode A. Biofabrication. 2022;14(4): 045019, reproduced under the terms of Creative Commons Attribution 4.0 license). D High cell density tissue with vascular network (from You S, Xiang Y, Hwang HH, et al. Sci Adv. 2023;9(8):eade7923, reproduced under the terms of Creative Commons Attribution license)

Fig. 3

Multiple nozzles or reservoirs for multi-material bioprinting. A each nozzle corresponding to one component of tissues (Reproduced with permission. Copyright 2014, WILEY‐VCH Verlag GmbH & Co.); B different bioinks in each reservoir can be deposited in specific area (Reproduced with permission. Copyright 2016, WILEY‐VCH Verlag GmbH & Co.)

Fig. 4

Novel structure in nozzle for multi-material bioprinting. A Using spiral valve to mix different materials (from Chávez-Madero C, de León-Derby MD, Samandari M, et al. Biofabrication. 2020;12(3):035023 Reproduced under the terms of the Creative Commons Attribution 4.0 license.); B using co-axial nozzle to print different bioinks simultaneously (Reproduced with permission Copyright 2017, American Chemical Society)

Fig. 5

Transition of bioinks for multi-material DLP bioprinting. (A) changing the bioink container after printing specific layers (from Orellano I, Thomas A, Herrera A, et al. Adv Funct Mater. 2022;32(52):2208325. Reproduced under the terms of the Creative Commons Attribution- NonCommercial License.); B rapid switch of bioinks by a pneumatic-driven pump (Reproduced with permission Copyright 2018, WILEY‐VCH Verlag GmbH & Co.)