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  1. If you are interested in learning about advanced digital technologies in head and neck reconstruction please check out this conference website: http://www.adt-conference.com/ The 2017 ADT meeting is hosted by the Facing Faces Institute in Amiens and will help identify and explore the future role of innovative digital technology in head and neck reconstruction. Between a myriad of advanced emerging technologies, specific focus will be placed on: Advanced Applications in Head and Neck Reconstruction Bernard Devauchelle, MD, PhD (Amiens, France) Biomaterials and Tissue Engineering Stephen Feinberg, MD, PhD (Ann Arbor, USA) Theragnostic Applications of Magnetic Nanoparticles Florence Gazeau (Paris, France) The Parametric Human Project Azam Khan, PhD (Toronto, Canada) The conference will cover a range of topics that address advanced digital technology in relation to head, neck, and cranio-maxillo-facial reconstruction. Let me know if you have any questions!
  2. Tissue engineering can't expand into three dimensions as long as cells can't access oxygen and nutrients via blood vessels. This remains a big challenge for the printable organ and tissue engineering communities. Monica Moya and Elizabeth Wheeler, biomedical engineers at Laurence Livermore National Laboratory, are working on a way to solve this “plumbing problem,” as Moya puts it, using 3D bioprinting. Moya has previously developed microfluidic devices to test the effect of mechanical cues on vessel growth, and published her work in the journal Lab on a Chip. Now she and Wheeler are collaborating on moving to a 3D printing platform. Lawrence Livermore National Laboratory published a blog post last month describing their recent work. First, they had to make sure that the printing techniques were compatible with cell viability. They had to change out the extrusion and fluidic parts of a standard 3D-printer, to eliminate the high temperatures and shear forces that would kill the cells. The bioink, a fluid with biological components, contains endothelial cells, fibrin, and fibroblast cells. The viscosity had to be finely controlled, so that it would remain liquid inside the printer, and gel once in contact with the bed, to print out the tissue support for the vessels. To make tubular vessels, a mixture of alginate (a polysaccharide isolated from seaweed) and fibroblast cells, is printed from a coaxial needle (a needle within a needle) resulting in printed vessel structures, called biotubes. Finally, more tissue bio-ink is laid down, enveloping the biotubes. The biotubes are hardened by flowing calcium solution through the tubes. The tissue patch starts to grow its own vessels, but it looks like spaghetti, with no organization. The alginate and calcium tubes eventually dissolve, leaving the vessels formed by the cells. Future planned developments include directing the vessel formation with nutrient and mechanical cues. The youtube video demonstrates the printing process: The photo above shows Monica Moya holding a dish with several of these biotubes. She explained their reasoning, “If you take this approach of co-engineering with nature you allow biology to help create the finer resolution of the printed tissue. We’re leveraging the body’s ability for self-directed growth, and you end up with something that is more true to physiology. We can put the cells in an environment where they know, ‘I need to build blood vessels.’ With this technology we guide and orchestrate the biology.” Moya and Wheeler did an AMA on Reddit back in December to discuss their work with interested members of the public. They have made tissue patches the size of one square centimeter, the size of a fingernail. Future directions include larger tissue patches. Potential applications of this work include drug testing, toxicology studies, and implantable tissues. Moya and Wheeler’s work is part of a larger project called iCHIP (in vitro Chip-based Human Investigational Platform) looking to create a “human on a chip” where different teams are working on making tissue models of the stomach, liver, heart, kidney, brain, blood–brain barrier, immune system, and lungs, also described in a blog post on the Lawrence Livermore National Laboratory website. Photo credit: Lanie L. Rivera Lawrence Livermore National Laboratory
  3. Following the current interest and significant recent advances in three-dimensional printing, the field of tissue engineering is increasingly seeking to adapt this technology for the fabrication of biological tissues, and potentially entire organs, for clinical transplantation. Despite significant demand for vascular grafts for clinical procedures such as coronary bypass surgery, the manufacture of synthetic blood vessels has proved to be problematic. Due to a tendency to cause thrombosis and a lack of growth potential, failure is not uncommon for conduits produced from conventional materials, especially in smaller diameter vessels. As a result, there is great interest in the development of a tissue engineered alternative, and three-dimensional bio-printing may hold the solution. Freeform droplet-based laser bio-printing is an orifice-free printing approach which has been used to generate straight and branched cellular tubes, the fundamental component of engineered blood vessels. As droplet-based laser printing does not require a nozzle, it is particularly well suited to handling the viscous bio-inks often required for tissue engineering purposes without the risk of clogging. By utilising an alginate hydrogel bio-ink capable of carrying a population of living cells, researchers from the University of Florida and Tulane University have printed straight and bifurcated (Y-shaped) tubular structures, demonstrating the promise of 3D-printing technologies for vascular tissue engineering applications. The generation of branched structures is of particular value as these are a fundamental component of native vasculature. Layer-by-layer deposition of droplets of either an 8% alginate solution or a 2% alginate-fibroblast cell suspension was printed following a predesigned pattern. A Z-platform was used to lower each deposited layer, step-wise, into a CaCl2 crosslinking solution to induce gelation of the printed alginate, with each step being the same depth as the height of the previous layer of un-gelled alginate. Initially, acellular straight-line tubes were printed to similar dimensions as human blood vessels, 170 individual layers built over 30 minutes to a height of 5.1mm, to form a tube with an internal diameter of 5mm. Subsequently, 5mm long, 45° Y-shaped tubes were produced, utilising the buoyancy provided by the calcium chloride crosslinking solution to support the formation of overhanging and spanning structures, and taking around two hours to complete. With the printing conditions thus optimised the team then introduced cellular bio-ink into the printing process and reproduced both straight and Y-shaped constructs with an incorporated live cell population. Loading the alginate solutions with cells appeared to disrupt droplet formation to an extent, leading to an increase in the minimum thickness of the vessel walls that could be produced, but the cell viability was considered to be acceptable for a printed bio-ink, and cell numbers were shown to increase over a 24 hour incubation, suggesting that the cells were healthy and proliferative following the bio-printing process. As well as successfully demonstrating the potential of droplet-based laser bio-printing for the tissue engineering of blood vessels and similar tubular structures, this work represents the first example of an overhang being incorporated into a cellular bio-printed construct. Although further development and eventual clinical testing will ultimately be required to determine the suitability of these three dimensional printed blood vessels for therapeutic use, this success brings us a step closer to the use of viable 3D-printed constructs in life-saving vascular graft surgery. Image Credits: http://cellimagelibrary.tumblr.com Biofabrication
  4. Scientists at the Wake Forest Institute for Regenerative Medicine in North Carolina, USA, have taken the next step towards printing living replacement parts for our bodies. In a study published in the February 15th edition of Nature Biotechnology, the scientists revealed the ITOP (Integrated Tissue-Organ Printer). This 3D printer, which has been in development for over 10 years, is able to form structured living tissue, including ears, bones and muscles, which look and function like the real thing. One of the biggest hurdles currently for printing body parts involves giving them the right shape and structure, rather than just making a mass of biological goop. Unfortunately, human cells are extremely sensitive, and many of the components that a 3D printer could use to give structure are also toxic, preventing the replacements from living happily over the long-term. However, the team came up with a specific layering pattern incorporating two key pieces of technology. The first breakthrough is the optimised layering of two scaffolding materials, with each material having a part to play in generating the final living structure. One of the materials is very strong but toxic, and gives the body part its overall structure during the printing process, before being washed away immediately afterwards. In the meantime, the second material has been held in place by the shell, and has had the time it needs to harden. This material gives long-term stability to the living tissue without toxicity. Eventually it will be replaced by the body part’s own secretions, making it just like those we can already find in our bodies. The second key technology is the incorporation of empty tunnels within the layers. These allow the transfer of life-giving oxygen and nutrients throughout the living tissue. The team was able to 3D print an ear, small pieces of bone, and some muscle tissue. More importantly, all of these retained their structure, and carried out their basic functions. For example, the 3D-printed bone produced calcium, the ear produced cartilage, and the muscle rearranged itself into the proper structure for exerting force. These beginning steps set the stage for the next phase in custom-printing replacement body parts. Many hurdles still stand between the ITOP and its use in healthcare, such as figuring out how well the body tolerates the 3D printed replacements. However the research of this team is a huge step toward printing living, functioning replacements for our bodies. And the advantage of 3D-printing compared to other techniques is the extreme level of control, both over the construction of the replacement, and the tailoring of each piece to suit the subject perfectly. Image Credits: Science BBC
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