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- 1. INTRODUCTION Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology. HOW DOES IT ALL WORK? Just like the complex, multi-cellular tissues found within a living person, 3D bioprinted living human tissues are highly dynamic. New cells are created through cell division; they mature and integrate into the tissue, forming connections with surrounding cells and contributing functionality throughout their lifespan.They become Dynamic tissues that self-organize and exhibit natural metabolic functioning . Bioprinting enables construction of tissues layer by layer, ensuring that each layer contains the relevant cell type(s) and has dimensions that approximate those of native tissue. When multiple cell types are present and organized properly, tissue-specific functions are often enhanced.But it's actually not a new field. Interestingly, this is a book that was published back in 1938. It's titled "The Culture of Organs." The first author, Alexis Carrel, a Nobel Prize winner. He actually devised some of the same technologies used today for suturing blood vessels.In Bioprinting, instead of
- 2. using ink, we're using cells.We can actually see the printhead going through and printing a structure. There's a 3D elevator that then actually goes down one layer at a time each time the printhead goes through. And then finally you're able to get that structure out. You can pop that structure out of the printer and implant it. So the strategy here is – we take a CT scan, an X-ray -- and we go layer by layer, using computerized morphometric imaging analysis and 3D reconstruction to get right down to those patient's own organs. We then are able to actually image those, do 360 degree rotation to analyze the organ in its full volumetric characteristics, and we then are able to actually take this information and then scan this in a printing computerized form. So we go layer by layer through the organ, analyzing each layer as we go through the organ, and we then are able to send that information,to the computer and actually design the organ for the patient. WHY YOU SHOULD LISTEN There's actually a major health crisis today in terms of the shortage of organs. The fact is that we're living longer. Medicine has done a much better job of making us live longer, and the problem is, as we age, our organs tend to fail more, and so currently there are not enough organs to go around. In fact, in the last 10 years, the number of patients requiring an organ has doubled, while in the same time, the actual number of transplants has barely gone up. So this is now a public health crisis. 90 percent of the patients on the transplant list are actually waiting for a kidney. Patients are dying every day because we don't have enough of those organs to go. That's where this field comes in that we call the field of regenerative medicine. It really involves many different areas. You can use, actually, scaffolds, biomaterials -- they're like the piece of your blouse or your shirt -- but specific materials you can actually implant in patients and they will do well and help you regenerate. Or we can use cells alone, either your very own cells or different stem cell populations. Or we can use both. We can use, actually, biomaterials and the cells together. And that's where the field is today. Anthony Atala is the director of the Wake Forest Institute for Regenerative Medicine, where his work focuses on growing and regenerating tissues and organs. His team engineered the first lab- grown organ to be implanted into a human -- a bladder -- and is developing experimental fabrication technology that can "print" human tissue on demand. pic :Surgeon Anthony Atala ,using a 3D printer technology,gave a young patient Luke Massella an engineered bladder 10 years ago; BIOPRINTING ADVANTAGES The potential benefits of 3D culture systems, especially those that contain multiple cell types, are recognized in several fields, including oncology, stem cell and developmental biology, cardiology, and hepatology. Efforts have been underway for many years to develop 3D culture systems that recapitulate native tissue form and function. Patterning techniques have allowed two or more cell
- 3. types to be placed in discrete locations relative to each other, thereby achieving compositional complexity in monolayer cultures . Bioprinting platform uniquely enables thick tissues (often >500 microns in thickness) to be constructed with spatial control in the x, y, and z axes, such that tissue-specific patterns or compartments can be produced that mimic key aspects of in vivo native tissues. Furthermore, because bioprinted tissues are created without dependence on integrated scaffolding or hydrogel components, they have a tissue-like density with highly organized cellular features, such as intercellular tight junctions and microvascular networks. Automated and Reproducible-The high-precision, automated instrumentation ensures reproducibility among bioprinted tissues through tight control of both the composition of the tissue and the geometry. Tissues can be fabricated directly into a wide variety of cultureware or custom chambers designed to maintain and condition 3D tissues, thus minimizing the need for manipulations that can introduce variability. 7 AMAZING USES OF 3D PRINTING IN MEDICINE (WHICH HAVE BEEN ACHIEVED) 1.Printing organs (Credit: 3Dscience.com)Can we grow organs instead of transplanting them? That was the question surgeon Anthony Atala asked during a TED talk in 2010 that went viral. Ten Years ago, Atala, who directs the Wake Forest Institute for Regenerative Medicine, took stem cells from a patient with a failing bladder, grew a new bladder and transplanted it into the patient. Atala's more recent efforts have focused on printing organs, and he has since demonstrated an early experiment to print a transplantable kidney. 2.Studying cancer with printed cells (Credit: BioMedical | Shutterstock)Printing cells could lead to better ways of studying diseases in the lab and then developing therapies. For example, one group of researchers used an automated system to print ovarian cancer cells onto a gel in a lab dish where the cells could be grown and studied. The printing approach could enable scientists to study the tumor cells in a more systematic environment and use them to test out drugs. The study, led by biomedical engineer Utkan Demirci, of Harvard University Medical School and Brigham and Women's Hospital, was detailed in February 2011 in Biotechnology Journal. 3.Printing cartilage & bone
- 4. (Credit: alxhar | Shutterstock)The skeletal system has also become a popular focus of 3D cell- printing efforts. In 2011, the same group from Germany that made the skin used laser printing to create grafts from stem cells that could develop into bone and cartilage. The work was published in January 2011 in the journal Tissue Engineering Part C: Methods. 4.Patching a broken heart (Credit: Broken heart image via Shutterstock)Researchers are working on developing a "heart patch" made of 3D-printed cells that could repair damaged hearts. Ralf Gaebel of the University of Rostock, Germany, and colleagues made such a patch using a computerized laser-based printing technique. They implanted patches made of human cells in the hearts of rats that had suffered heart attacks; the rats' hearts that were patched showed improvement in function, the scientists reported in December 2011 in the journal Biomaterials. 5.Printing skin The last 25 years have seen great advances in creating tissue-engineered skin, which could be used to replace skin damaged from burns, skin diseases and other causes. Recently, scientists have added 3D printed skin to their repertoire. Lothar Koch of the Laser Center Hannover in Germany and colleagues laser-printed skin cells, as reported September 2010 in the journal Tissue Engineering Part C: Methods. 6.Printing blood vessels & heart tissue (Credit: Fraunhofer IGB)Printing some tissue types is already a reality. Gabor Forgacs from the University of Missouri in Columbia and colleagues printed blood vessels and sheets of cardiac tissue that "beat" like a real heart. The work was published in March 2008 in the journal Tissue Engineering. Forgacs and others started a company called Organovo to bring these products to market.A group at the German Fraunhofer Institute has also created blood vessels, by printing artificial biological molecules with a 3D inkjet printer and zapping them into shape with a laser. 7.Printing human embryonic stem cells (Credit: M. Nakamura, Bioprinting Project, Kanagawa Academy of Science and Technology)Stem cells, those magical cells that can develop into many different kinds of tissue in the body, can now be printed, at least in the lab. In a study published Feb. 5, 2013, in the journal Science, researchers from the University of Edinburgh describe a valve-based cell printer that spits out living human embryonic stem cells. The cells could be used to create tissue for testing drugs or growing replacement organs, the scientists report. CASE STUDY 1 TO CREATE 3-D TISSUES AND ORGANS USING STEM CELLS AS THE "INK." Human embryonic stem cells(collected during the birth of a baby,which can grow into any organ of the body,treat diseases etc),can be printed out with a valve-based printing technique, tailored to account for the cells' delicate properties. The cells were loaded into two separate reservoirs in the printer and were then deposited onto a plate in a pre-programmed, uniformed pattern.
- 5. Using stem cells as the "ink" in a 3-D printer, researchers in Scotland hope to eventually build 3-D printed organs and tissues. A team at Heriot-Watt University used a specially designed valve-based technique to deposit whole, live cells onto a surface in a specific pattern. The cells were floating in a "bio-ink," to use the terminology of the researchers who developed this technique. They were able to squeeze out tiny droplets, containing five cells or fewer per droplet, in a variety of shapes and sizes. To produce clumps of cells, the team printed out cells first and then overlaid those with cell-free bio-ink, resulting in larger droplets or spheroids of cells. The cells would group together inside these spheroids. Spheroid size is key, because stem cells need certain conditions to work properly. This is why very precisely controlled 3-D printing could be so valuable for stem cell research. CASE STUDY 2 Researchers 3D Print MicroSwimmers & BioRobots to Carry Cargo Inside Human Body, Fueled by Cells If we can 3D design and 3D print in a really big way, it is of course entirely possible to do things on the less flashy but microscopic level as well, scaling down all these big ideas, and both controlling and improving some of the functions inside the greatest challenge of all: the human body.As 3D printing has progressed, it has been connected more and more with robotics, the 3D printing of robotics, and even what robots can do in performing 3D printing activities themselves — as machines capable of handling complex, tedious, repetitive exercises and tasks. Robots can be scaled up or down — and they can often go where we cannot. Thus is the subject of a research paper by M. M. Stanton, C. Trichet-Paredes, and S. Sánchez titled “Applications of Three- dimensional (3D) Printing for Microswimmers and Bio-Hybrid Robotics” recently published in The Royal Society of Chemistry 2015. 3D printed microswimmers that would be mobile in a way similar to bacteria rotating in movement, as well as carrying ‘cargo.’ • Fully functional and stable for >40 days pic: comparison of a human kidney performance with an engineered kidney(hydroxymidazolam formation )
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