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3D-printed antimicrobial teeth, blood vessels, heart valve made with co-polymer hydrogels

3D-printed antimicrobial teeth, blood vessels, heart valve made with co-polymer hydrogels

29-Jul-16

All implants in medicine suffer from biofilm formation, so giving them antibacterial properties would be beneficial. Hence the process of 3D printed antimicrobial medical devices has even wider applications. With the advent of 3-D bioprinting, cells can now be dispensed from the printer onto a biologically compatible scaffolding, layer by layer, to create a three dimensional viable tissue. Recently, researchers have found some amazing healthcare and biological applications for 3-D printing technology, called bioprinting. From custom prosthetics to living tissue, 3-D printing is a versatile means of providing cost effective and individualized care to patients. Biomaterials have been adapted for 3-D bioprinting, including co-polymer hydrogels. Alginate, for example, is a naturally occurring anionic polymer with many attractive features for biomedical applications, including low cost, excellent biocompatibility, low toxicity, and a variety of cross-linking capabilities.

The current status quo of dental fillings and implants could face a significant overhaul in the coming years, thanks to the advent of 3D printing. Researchers in the Netherlands have successfully created a 3D-printed tooth implant made from an antimicrobial resin that kills harmful bacteria in the mouth- resulting in a tooth that effectively cleans itself. To test the efficacy of the antimicrobial plastic, the researchers coated samples of the resin in a mixture of the saliva and Streptococcus mutans bacteria - a significant contributor to tooth decay. The antimicrobial material killed 99% of the bacteria, whereas a sample of untreated resin resulted in 99% of the bacteria remaining. Chemistry professor Andreas Hermann, who leads the polymer chemistry and bioengineering group at Groningen, and Yijin Ren, head of the university's orthodontic department, agreed that they could go a step further. Hermann says. "We designed the materials in such a way that once bacteria settle on the material the positively-charged groups make holes in the microbes and the bacteria then die." Then, they printed the teeth using a Formlabs Form 1 3D printer and a process called stereolithography, which involves depositing the liquid polymer into a mold, layer by layer, and then hardening it with a laser. To make it work, the viscosity of their antimicrobial plastic had to be the same as a conventional one. Herrmann: 'We have tested printed objects with saliva. All the components are already being used in humans, but more tests are needed before we can bring these 3D antimicrobials to the market.' The first applications will probably be in orthodontics, where 3D printed retainers and aligners are already in use. In the longer run, 3D printed crowns with antimicrobial properties could be an option.

In what may be a critical breakthrough for creating artificial organs, Harvard researchers say they have created tissue interlaced with blood vessels. Using a custom-built 4-head 3-D printer and a "disappearing" ink, materials scientist Jennifer Lewis and her team created a patch of tissue containing skin cells and biological structural material interwoven with blood-vessel-like structures. Reported by the team in Advanced Materials, the tissue is the first made through 3-D printing to include potentially functional blood vessels embedded among multiple, patterned cell types. All current regenerative projects have faced the same problem when trying to build thicker and more complex tissues: a lack of blood vessels. Lewis's group solved the problem by creating hollow, tube-like structures within a mesh of printed cells using an "ink" that liquefies as it cools. The tissue is built by the 3-D printer in layers. A gelatin-based ink acts as extracellular matrix-the structural mix of proteins and other biological molecules that surrounds cells in the body. Two other inks contained the gelatin material and either mouse or human skin cells. All these inks are viscous enough to maintain their structure after being laid down by the printer. A third ink with counter-intuitive behaviour helped the team create the hollow tubes. This ink has a Jell-O-like consistency at room temperature, but when cooled it liquefies. The team printed tracks of this ink amongst the others. After chilling the patch of printed tissue, the researchers applied a light vacuum to remove the special ink, leaving behind empty channels within the structure. Then cells that normally line blood vessels in the body can be infused into the channels.

A critical requirement for tissue-engineered heart valves is that the engineered valve must be able to mimic the physiological function of the native valve, including the natural geometry and performance of the valve root, cusps, and sinus wall, all of which are essential for healthy coronary blood flow. Tissue-engineered heart valves must also have the same intrinsic asymmetry as the root, which prevents cusp deterioration. 3-D "bioprinting" technology has been used by researchers at Cornell University to fabricate living heart valves that possess the same anatomical architecture as the original valve. This research is described in a paper by Jonathan T. Butcher, associate professor of biomedical engineering at Cornell University, and others published in the Journal Biomedical Materials Research. Biomaterials have been adapted for 3-D bioprinting, including co-polymer hydrogels. "Alginate-based hydrogels are particularly attractive for bioprinting because of their broad range of viscosities at room temperature," says Butcher. "This is important because hydrogels have tight requirements with regard to viscosity and gelling speed for accurate printing." Butcher's team conducted bioprinting that utilized an alginate/gelatin hydrogel system that included smooth muscle cells and valve interstitial cells. A dual-syringe system was used to mimic the structure of the valve root and leaflets, two key valve structures. The team successfully fabricated living aortic valve conduits with strong anatomical resemblance to the native valve. The results demonstrate that anatomically complex, heterogeneously encapsulated aortic valve hydrogel conduits can be fabricated with 3-D bioprinting.
"3-D tissue printing combines the disciplines of quantitative image analysis, computer-aided design, and manufacturing to develop a real entity-in this case, a living tissue-in a fraction of the time that any other traditional mechanical engineering process would," says Butcher. "Many people may spend their entire thesis working on just one part of this process, but without performing the whole process to completion, they won't know how to improve the system. Researchers gain a much greater appreciation for this systematic approach and can build a larger toolset, while having much more fun being creative in the process." Butcher believes bioprinting will gain much more traction in the tissue engineering and biomedical community over the next five years, "potentially even becoming the standard in complex tissue fabrication," he adds. "I hope that people use this technology in the future to target a higher level of tissue complexity, like glandular and highly vascularized and innervated functional tissues."

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