Genetic Engineering & Biotechnology News

DEC 2017

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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24 | DECEMBER 2017 | | Genetic Engineering & Biotechnology News See 3D Bioprinting on page 26 dosage. Dr. Roberts said this concept resembles the role of compounding pharmacies, and from a legal and regulatory perspective, could operate in a similar fashion. One company, Aprecia Pharmaceuticals, is already using 3D-printing technology to make medicines. Aprecia's Zip- Dose ® platform produces a tablet by depositing a powder blend containing the drug in a layer. Then, an aqueous binding fluid is applied over the powder, forming a solid tablet that dis- solves very easily, for patients who have difficulty swallowing. Dr. Roberts said that his group has demonstrated suc- cessful formulation of drug tablets using 3D extrusion and inkjet-based printing. In a 2015 article in International Jour- nal of Pharmaceutics, he describes the creation of 3D printed tablets for the drug captopril and a combination of nifedip- ine and glipizide. 1 An osmotic pump was incorporated into the captopril tablet, and the nifedipine/glipizide tablet was printed with sustained-release compartments. According to Dr. Roberts, 3D-printed tablets can be very complex, presenting exciting opportunities for formulation. "There is essentially no solid formulation that can't be repro- duced in some fashion," he said. Human-on-a-Chip In vitro systems that can reproduce the functionality of human organs have been the subject of research and de- velopment efforts in biotechnology for many years. These systems have the potential to streamline drug development and eliminate or minimize animal testing. In his keynote pre- sentation, "Building Phenotypic Body-on-a-chip Models for Toxicological and Efficacy Evaluations in Drug Discovery as Well as Precision Medicine," James Hickman, Ph.D., a professor at the University of Central Florida, outlined his progress in developing phenotypic body-on-a-chip models for drug development and precision medicine. Dr. Hickman published his first papers on cell printing in 2003–2004, 2,3 and has incorporated the technique into current human-on- a-chip protocols. His low-cost gravity-driven flow system for human cardiac, liver, skeletal muscle, and neuronal cells demonstrated survival and continued functionality of all cell types over a 14-day period. Hickman has already been working extensively with L'Oreal—a company that is not allowed to use animals for developing cosmetic products under European Union regula- tions—to develop body-on-a chip systems for the develop- ment of cosmetic products. Dr. Hickman's presentation ad- dressed how the body-on-a-chip system could be integrated into drug discovery by enabling efficacy and toxicity studies in the same system. "They're going to lower the cost eventu- ally for drug development. One of the biggest reasons they'll be able to get the success rate higher [is] by being able to weed out compounds that eventually will be unsuccessful earlier in the process," said Dr. Hickman. A body-on-a-chip system is illustrated in Figure 1. The Importance of Phenotype An often overlooked consideration in 3D printing of cell-based constructs is the phenotype and biological char- acteristics of the primary cells. In his presentation, "The Im- portance of Cell Phenotype in 3D Printing," Ali Mobasheri, D.Phil., a professor at the University of Surrey, U.K., spoke about phenotype in the context of 3D printing cartilage-like tissues. This type of tissue could be used in the near future to engineer transplants for focal defects in damaged joints. Phenotypic appearance of liver, pancreas, and cartilage cells in vivo are shown in Figure 2. According to Dr. Mobasheri, phenotype plays into that technology in two ways. First, the cells have to have the proper phenotype to use in the 3D construct. For example, if the construct will be comprised of bone, the proper pheno- type bone cells must be chosen as starting material. Second, the phenotype also must fulfill requirements of immune tol- erance and acceptability by the patient. "What you want is cells that could be used to fill that gap, and not be rejected by the patient's immune system," said Dr. Mobasheri. A stable phenotype is important in other 3D-printing ap- plications, as well. Dr. Mobasheri said that when 3D printing tissue for drug screening, the phenotype must be correct for the application. For example, if 3D-printed liver tissue is go- ing to be used to screen drugs for a condition like hepatitis or for treating alcohol-induced liver damage, the phenotype of the liver cells used in the construct must replicate the behav- ior of the living organ. Next-Level Skin Grafts 3D-printing platforms for human skin have attracted a lot of interest for their use as grafts for burns or chronic wounds. Pankaj Karande, Ph.D., associate professor of chemical and bio- logical engineering with the Rensselaer Polytechnic Institute, 3D-Bioprinting Conference Showcases Versatility Figure 1. Hesperos measures functional parameters of tissues in multi-organ systems in situ. The system shown is a four-organ body-on-a-chip device with four distinct functional tissues, in which the liver acts upon added compounds through metabolic pathways. Mechanical function of muscle tissues, in this case, cardiac muscle and skeletal muscle, are measured with microscale cantilevers, and electrical activity and conduction in cardiac tissue and neurons are measured using arrays of microscale electrodes. Photo courtesy of Hesperos, Inc. Translational Medicine Feature Continued from page 1

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