Genetic Engineering & Biotechnology News

DEC 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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20 | DECEMBER 2018 | Genetic Engineering & Biotechnology News | the demand and the supply of organs for transplantation. De- velopments in 3D bioprinting technologies have made pos- sible the printing of relatively simple tissues and structures— sheets of skin or cardiac patches, for example. As the technol- ogy matures, more complex organs, such as the retina, liver, and lungs, may follow. Although researchers are still working to print (and gain FDA approval for) functional human organs, 3D bioprinted tissues already have found numerous applications in drug discovery, testing drug toxicity, tissue engineering, consumer product testing, bone transplants, and cosmetic dentistry. The advantages of 3D bioprinting, when compared with other tissue fabrication techniques, include fabrication of anatomically correct shapes, fabrication of porous struc- tures, use of multiple cell types, and controlled delivery of growth factors and genes. One of the biggest challenges to overcome includes driving down the resolution of the print- ing technique enough to enable vascularization of tissues and organs. The possibilities and challenges of this exciting field were discussed at the SelectBIO: 3D-Bioprinting and Tissue Engi- neering conference held recently in Boston. A handful of the scientists who spoke at the conference also discussed their research and insights on bioprinting and tissue engineering with GEN. He Who Controls the Ink… While a primary focus of the early days of the 3D bio- printing revolution has been advancing printer technology, the thing that the printer spits out—the ink—has received far less attention. That's where Boston-based company Cellink comes in. "When I started the company, I realized that there were a lot of printer manufacturers building expensive systems," said Erik Gatenholm, co-founder and CEO at Cellink. "But nobody had taken the approach of focusing on the inks." Gatenholm saw a wide-open opportunity to design and commercialize a suite of standardized biomaterials for bio- printing human tissues and organs. Cellink's bioinks consist of variety of materials—includ- ing gelatin, collagen, alginate, or other natural polymers— and infused with human cells. The inks are custom-designed for specific tissue types and are compatible with the majority of 3D bioprinters on the market. When Gatenholm first launched Cellink in 2016, he tried to partner with 3D printing companies or bioprinting companies, but none wanted to collaborate with such an early-stage company. So, Cellink decided to develop its own cost-effective, mobile line of printers. Coupled with the firm's bioink, Cellink now offers complete 3D bioprinting package solutions for customers, which primarily include academic institutions and pharmaceutical companies. The company has at least 500 systems in use in labs around the world. Gatenholm said that although Cellink's bioinks are cur- rently mostly used to create tissue for the purpose of re- searching and developing new drugs, they have the potential Technologies for 3D bioprinting are already being used to fabricate relatively simple articial tissues and structures such as cartilage, skin, and bone, as well as blood vessels and cardiac patches. (This image depicts a 3D bioprinted vertebra in a petri dish.) As 3D bioprinting technology matures, it may be used to fabricate complex organs such as retina, liver, and lungs. Dr_Microbe / Getty Images Translational Medicine Layer by Layer: 3D Bioprinting on the Rise Continued from page 1 Although approximately 17,000 patients in the U.S. are on the waiting list for a liver transplant, only 6000 liver transplants are performed each year. For patients awaiting a liver transplant, a 3D bioprinted liver tissue may help extend survival until a liver is available. Using its 3D bioprinting technology, Organovo has developed a liver therapeutic tissue, called Novo- Tissues ® , which demonstrated robust function in two models of rare liver diseases, 1) α-1 antitrypsin de'- ciency (AATD) and 2) hereditary tyrosinemia type 1 (HT-1), says Benjamin Shepherd, Ph.D., senior director, therapeutics, Organovo Holdings. Organovo's technology incorporates human liver cells into a printable bio-ink to generate sections of liver tissue by the controlled patterning and deposi- tion of speci'c cell types. The formed tissues exhibit dense cellularity and develop extensive cell–cell in- teractions akin to native tissue, resulting in prolonged tissue viability and function outside of the body, according to Dr. Shepherd. These tissues are then im- planted into the setting of established animal models of liver disease to test for safety, therapeutic e›cacy, and viability. Organovo's NovoTissues for the treatment of AATD was granted orphan drug designation by the FDA in 2017. When the bioprinting technique was evaluated in a model of AATD, the implanted tissues rapidly en- grafted, demonstrated graft retention, and displayed clear evidence of disease modulation through a 90- day evaluation, notes Dr. Shepherd. Characterized by a patient's inability to metabolize the amino acid tyrosine, HT-1 causes severe liver dam- age, and current treatment options are often limited to organ transplantation. Organovo's bioprinted liver tissue demonstrated retention and sustained func- tionality postimplantation in mouse models of this rare inherited disease, notes Dr. Shepherd, adding that the diseased animals showed improvement in liver health and extended survival compared to non- treated animals. "The success of Organovo's bioprinted therapeutic tissue in the above preclinical studies highlights its applicability in treating conditions like HT-1 and AATD, where there is critical unmet need for progressive, novel therapies," says Dr. Shepherd. Q Treating Rare Liver Diseases with 3D Bioprinted Tissue

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