| | JUNE 20199CIOReviewmethods and bioinks. Bioprinting exists as 2D bioprinting (laying down a monolayer of living cells with a bioprinter), 3D bioprinting (erecting 3D cell-containing structures), and 4D bioprinting. 4D bioprinting is the creation of 2D or 3D objects specifically engineered to respond in predicted, anticipated ways to user-demands or a changing environment. The response is a self-actuated shape-morphing, cellular differentiation, tissue patterning, biological characteristic alteration or functionality development.· You've mentioned digital biomanufacturing. What will this provide for bioprinting?Like digital manufacturing in the parts and equipment world, digital biomanufacturing improves the manufacturing of biological products by using the newest computer-aided design and manufacturing technologies. Digital approaches here include such advances as cloud-based applications, machine learning, artificial intelligence and autonomation. In 3D bioprinting some are now generating digital (in silico) models to simulate and analyze the printer's activity and input materials, with the goal of guiding and optimizing the printing process. Instruments monitoring and controlling these activates are becoming interconnected, with more and higher quality data being collected. Monitoring is improving, analysis is becoming richer, and models are beginning to describe a true predictive control-based "process network".· What are some of bioprinting's specific products, applications, and markets?Well, that's a big and exciting question and can only be outlined here. 3D bioprinting is supporting basic research in such applications as creating cell, tissue and organ models of both nature and function. It is being applied in medical research in many types of advanced cell-based assays for clinical diagnostics and models of a tissue's response to therapy. 3D printed structures have been reported to provide the best biomimetic modeling of natural tissues for viral progression assays. They're being applied in clinical testing, assays and diagnostics­including companion diagnostics. In regenerative medicine, we are beginning to create synthetic tissues and organs for transplantation. Structures are already demonstrating great success include bioprinted heart valves, cartilage, cartilaginous tissues, trachea, skin and blood vessels.· What is the status of the commercialization of equipment and materials for bioprinting?There have been CMOs providing bioprinting services for some time, as well as the commercial availability of small, inexpensive printers for research--some of which even have options providing capability for small manufacturing processes. There are a few vendors larger 3D bioprinters capable of large-scale, high-throughput and regulated manufacturing. Each efficiently provides selected printing styles and production capabilities. As for materials, we are seeing more commercially available bioinks and bioink-qualified components. Beyond nutrient and shear-protection components, bioink contains high-molecular weight polymers (either natural or synthetic) that mimic an extracellular matrix to support the adhesion, proliferation, and differentiation of the component cells.· What do you see in the future for bioprinting and in the applications you've identified?Each bioprinting technology has advantages and limitations. Some are very accurate and precise, others are fast and move much volume. Construct design is moving from rather simple to complex, and is now incorporating many substructures and cell-types. Therefore, bioprinting is moving from simple operations to model-controlled, multi-material, interpenetrating networks using multi-mode deposition techniques. Advances are rapidly occurring from the topology of the printed structures, to the types of material components employed, to the digital techniques applied in direct the printing. So, in the printing technology itself we envision that one day application of a cloud-based platform, such as GE's PredixTM, will enable powerful manipulation of data to better support the advancing complexity of bioprinting processes. As for products, there is no doubt that bioprinting will provide new multiwall assay formats of highly organized 2D structures, and elegant biomimetic 3D models of normal and diseased tissues. We are already seeing the design of bioartificial tissue replacement therapies fabricated from cell-seeded 3D printed bioartificial nanocomposites, as well as vascularized tissues developed from 4D bioprinting-based constructs. Like digital manufacturing in the parts and equipment world, digital biomanufacturing improves the manufacturing of biological products by using the newest computer-aided design and manufacturing technologies
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