Mar 11, 2016 | By Alec
Various research teams throughout the world are working hard to make 3D printed blood vessels, skin tissue and even whole organs a reality. Though progress is understandably slow, we are certainly heading in the right direction. Just earlier this week, Harvard researchers revealed their successes with embedding vasculature in 3D printed tissue. Now joining the fray are researchers from the Indiana University School of Medicine, who have gotten their hands on one of the most impressive existing 3D bioprinters: the Regenova by Cyfuse Biomedical, and will use it to pioneer 3D printed skin, inner ear and nipple tissue, among others, for use in regenerative surgery.
If the Regenova 3D printer sounds familiar, that’s probably because it’s one of the most innovative 3D bioprinters currently available. Its manufacturer Cyfuse Biomedical has been carving out its reputation as a biomedical pioneer for a few years now; back in 2015, their reputation helped them gather $12 million for 3D printed human tissue research, while their one-of-a-kind Regenova 3D printer ranks very well our Top 20 3D Bioprinters. That 3D bioprinter has also recently landed in San Diego, where it will also be used for tissue research.
So what makes that machine so interesting? Unlike most currently used competitors, the Regenova does not make use of scaffolds and fluids to ensure the correct placement of each cell. Instead, the Cyfuse Medical 3D printer uses an array of needles on which aggregates of cells called “spheroids” are skewered into their required position, like microscopic pieces of meat on tiny upright kebabs. These cells begin to interact organically and, once fully self-organized, can be freed from their needle supports, leaving a complete section of tissue. This technique has been labelled the Kenzan Method, “Kenzan” meaning “needle array” in Japanese.
Inside the Regenova, stainless steel needles can be found with a diameter of 100-200 micrometers and pitch of 300-400 micrometers. With it, the machine is able to sculpt biological patterns within a range of ~10x10x10mm at 500um resolution. Printed tissues are then able to be fused together to create larger constructs. Each tissue is precisely designed using the Regenova-specific “B3D” 3D design software, which allows users to manipulate the patterns of “spheroids” in a precise, controlled manner. According to Cyfuse Biomedical, this method offers notable advantages over other 3D bioprinting techniques, by reducing cell damage and increasing viability. Its “much gentler approach” eliminates high-velocity liquid flow, which can damage cells and yield low cell numbers. Thanks to the elimination of this factor, the technique is suitable even for the most delicate primary cells, which are often of the highest physiological relevance.
Researchers at Indiana University are now the second group in the US to have access to this innovative technology. According to associate vice chancellor for research David B. Burr (and professor of anatomy, cell biology and biomedical engineering), they will be using it to conduct research in a very varied range of fields that touch tissue engineering and regenerative medicine, from vascular and musculoskeletal biology to dermatology, ophthalmology and cancer. “We have a large and robust group of investigators in these fields who are interested in 3D bioprinting for aspects of their work,” he said. “Having this device positions us, and these investigators, to conduct research and obtain grant funding in new areas that many universities are simply not able to compete for yet.”
According to Dr. Nicanor Moldovan, one of the researchers who will be working with the machine, the Regenova’s tissue results will be far more likely to be approved by the Food and Drug Administration for human use in the future than other methods at their disposal. “Putting the printer in our hands immensely empowers us to do constructs no one has done before,” said the adjunct associate professor of biomedical engineering and of ophthalmology. In particular, they went for the Regenova 3D printer because it doesn’t force cells through nozzles – a method that can leave fragments of biogel in the nozzle.
It was the interest shown by Dr. Moldovan and colleagues, including Keith March, that was instrumental in reaching an agreement with Cyfuse. Under the agreement, the university will be leasing the $450,000 instrument while preparing a grant proposal for purchasing it. “There is a lot to be learned and gained on both sides from this relationship. I think it's very clear that Cyfuse is passionate about helping the researchers at IUPUI generate the best constructs possible to give the best chance of success,” said Cyfuse representative Steven Boikess.
Several research projects are already lined up for the Regenova 3D printer, once it arrives. Assistant professor Karl Koehler will use it to pioneer cranial tissues, such as inner ear and skin, while associate professor John Foley will explore nipple areola reconstruction using the machine. Assistant research professor Nutan Prasain are exploring blood vessel repair through the machine, while associate professor Melissa Kacena hopes to use it for bone construction. “Should this approach be successful, in the future we envision using the patients’ own cells to create a patient-specific, anatomically shaped bone segment to replace one that is missing due to injury or disease,” she said. Professor of biomedical and mechanical engineering Hiroki Yokota, finally, plans to use it to study the bone metastasis of cancer cells.
The machine is thus creating high hopes over at Indiana University, and Dr. Burr went as far as predicting that practically applicable 3D bioprinted tissue for the replacement of tissue suffering from traumatic injury is no less than a decade away. It will take some time, but medical 3D bioprinting is definitely coming, it seems.
Posted in 3D Printing Application
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