Phenotypically relevant generation of liver models through bioprinting

Liver tissue is generally divided into lobes, lobules, hepatocytes, and sinusoids. These structures are characterized by having a highly complex micrometric vascular network, where the whole tissue have a few millimeters in its thickness and several centimeters on its length.

To engineer multiscale heterogeneous tissues, a sophisticated and rapid tissue engineering approach is required. Even though bioprinting is always presented as an option for addressing structural problems when building tissues, its precision when extruding a tissue of few millimeters is on the range of 100s of micrometers, and therefore, being unable to recreate the complex micrometric vascular structure.

For that reason, our group developed an advanced bioprinting technique where the precision of more established techniques, such as classic printing or molding, is used to give the extra precision that bioprinting lacks. The technique, called preset bioprinting, was used to fabricate hepatic lobules including hepatic cells, endothelial cells, and a lumen. The endothelial cells surround the hepatic cells, the exterior of the lobules, the lumen, and finally, become interconnected with each other. Compared to hepatic cell/endothelial cell mixtures, made without the preset bioprinting, the fabricated hepatic lobule showed higher albumin secretion, urea production, and albumin, MRP2, and CD31 protein levels, as well as, cytochrome P450 enzyme activity.

Additionally, the use of the preset bioprinting device associated to microfluidics enabled the production of phenotypically relevant liver organoids. The structural integrity was maintained by several days engendering an increased performance of cellular function. Moreover, these micro-spheroids once injected into animals showed a better engraftment, bringing to light the importance of phenotypically relevant models not only for drug screening but also regenerative medicine.

Presented by Paulo André Marinho, Head of Scientific Strategy at T&R Biofab.

Interview

Question 1: What drives you?
The possibility to work with techniques and science that will impact people’s lives is what drives me.

Question 2: Why should the delegate attend your presentation?
Any delegate that is interested on state-of-the-art bioprinting techniques that could be used to address tissue engineering structure problems to improve efficacy or phenotype should attend the talk.

Question 3: What emerging technologies / trends do you see as having the greatest potential in the short and long run?
There is not one emerging technology that could be seem as the one with most potential. In my humble opinion, the combination of several technologies in a multidisciplinary context is the key to generate or innovate with regards to new medical products/solutions. On that sense, bioprinting associated to exceptional biomaterial and stem cell technology seems to be a combination that will certainly lead the biomedical devices in the near future.

Question 4: What kind of impact do you expect them to have?
The expectation is either to improve current used technologies, resulting into more efficient or safer products, or to generate completely new products that couldn’t be imagined 10 to 20 years ago.

Question 5: What are the barriers that might stand in the way?
3 points could be enumerated.
Firstly, proper investment associated with time are needed to develop these technologies.
Secondly, a more detailed discussion with regulatory agencies to educate and speed their process
Lastly, the support from big pharma/medical companies that benefit from their brand name, customers and marketing power to adopt and launch these technologies

About Paulo André Marinho
During his academic research, Paulo studied how to make Induced Pluripotent Stem Cells technology fully available for the scientific community using Bioreactors and Design of Experiments.

Afterwards, he spent 5 years in France together with L’Oréal, where he oversaw a group of Tissue Engineering, leading an international team working in several projects, among them: Bioprinting, New Artificial Skin Models, and Scaffolding. In 2017, he moved to South Korea, where he developed in vitro Hair Models with Amore Pacific.

Lastly, he became the head of scientific strategy in T&R Biofab; his activities are related to business development, scientific communication and strategy development about Bioprinting, Stem Cells and Biomaterials.

About T&R Biofab
T&R Biofab is a science-driven and product-oriented company which has developed and produced their own 3D Bio-printing System for the creation of biodegradable scaffolds, Bio-ink, 3D Organoid Models, Cytotherapeutic Agents, and Artificial Organs. Additionally
Currently, after securing key IP, filing over 100 patents, and expanding our area of research, using iPS cells and special biomaterials; T&R has the core technology to develop artificial organs such as skin, heart, and liver, having publications on the most renown scientific journals of the world (Biofabrication, Biomaterials, Small, Nature Communications, Advanced Materials, etc.)

Paulo André Marinho is speaker at the 2022 edition of the 3D Bioprinting Conference, part of the 3D Medical Printing Series.

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