3D Bioprinting
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 typical self-aggregated co-culture models.
Architecture of ExVive™ 3D Bioprinted Human Liver Tissue with distinct hepatocellular (HC) and non-parenchymal cell (NPC) compartments. The automated bioprinting process results in scalable tissues, with tight control of the composition and geometry.
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. Furthermore, under the right conditions, using diseased patient cells in bioprinted tissues can recapitulate the disease phenotype while healthy cells do not under the same conditions. This allows screening for targets and drugs to those targets that block disease progression in cells from an actual human patient with disease. We believe these drugs will be fundamentally more efficacious than drugs discovered using current methodologies.
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, our bioprinted tissues utilize primary human cells where possible in order to produce the in vivo-like physiology most relevant for drug testing. We utilize multiple independent sources for our input cells to allow patient selection and high levels of diversity.
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.
NovoGen Bioprinter® Platform
Our bioprinter technology has been used to create a spectrum of tissues: healthy liver, NASH liver, kidney, intestine, skin, vascular, bone, skeletal muscle, eye, breast and pancreatic tumor.
Sources:
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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.
