Technology Platform

3D Bioprinted Human Tissue

3D bioprinting is the automated fabrication of multicellular tissue via spatially defined deposition of cells. The ability to spatially control deposition in the x, y and z axes allows for creation of tissue-specific patterns or compartments, with in vivo-like architecture that mimics key aspects of native biology.

3D bioprinted tissues exhibit a microenvironment more suited to in vivo-like cellular function in comparison to traditional 2D monoculture (or monolayer co-cultures), as well as maintenance of a more defined architecture than is observed in self-aggregated co-culture models.

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Architecture of ExVive™ 3D Bioprinted Human Liver Tissue with distinct hepatocellular (HC) and non-parenchymal cell (NPC) compartments.

3D bioprinted tissues exhibit tissue-like density with highly organized cellular features, such as intercellular tight junctions and microvascular networks. The ability to create architectural compartments, with different cell types placed in discrete locations relative to each other, results in a microenvironment with cell-cell interactions similar to that of native tissues. This in turn results in proper expression and localization of key cellular functions – such as key metabolic enzymes and key transporters – over several weeks in culture. The responses of 3D bioprinted tissues to acute or chronic exposure of drugs and known toxins resemble what is observed in vivo and in the clinic.

The automated bioprinting process results in scalable tissues, with tight control of the composition and geometry. We have the capacity to produce thousands of tissues per month in our 6,000 sq ft clean manufacturing suite, to support our drug testing and therapeutics applications.

Bioprinting Process

Our bioprinting process starts with the identification of key architectural and compositional elements of a target tissue, and the creation of a design that can be utilized by a bioprinter to generate that tissue in the laboratory environment. The next step is to develop the bioprocess protocols required to generate the multi-cellular building blocks—also called bio-ink—from the cells that will be used to build the target tissue. While the bioprinting process is cell-agnostic, most of our bioprinted tissues utilize primary human cells in order to produce the in vivo-like physiology most relevant for drug testing and therapeutic applications. We source many of our input cells through our subsidiary, Samsara Sciences.

The bio-ink building blocks are then dispensed from a bioprinter, using a layer-by-layer approach that is scaled for the target output. Proprietary biogels may be incorporated for temporary support or as filler to create channels or void spaces within tissues to mimic features of native tissue. The bioprinting process can be tailored to produce tissues in a variety of formats, including micro-scale tissues contained in standard multi-well tissue culture plates. 

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Our bioprinter technology has been used to create a spectrum of tissues: liver, kidney, intestine, skin, vascular, bone, skeletal muscle, eye, breast and pancreatic tumor.

Sources:

Norona LM, et al. (2016) Tox Sci. 154(2):354-367
Nguyen DG, et al. (2016) PLoS One. 11(7):e0158674.
King SM, et al. (2017) Front Physiol. 8:123.
Madden LR, et al. (2018) iScience. 2:156-167