Connor Although, the materials and accuracy of

  Connor McLaughlin Ryan StackAidan LeeMajor introductions of 3D printing into Bioengineering Stereolithography or 3D printing was first introduced to the world in 1984 by a french team led by Charles W Hull. The idea quickly caught on among large corporations looking for a cheaper, faster and all around more efficient way to prototype industrial design products. The first 3D printer created by Charles W Hull costed around 100,000 dollars and could only print in low grades plastics to a relatively low accuracy. The printer was mainly used to make specific parts, purchased by companies outsourcing for a cheaper way to develop expendable prototypes. Although, the materials and accuracy of the first 3D printer did not show extreme promise the idea of being able to quickly, cheaply and easily customize any part that could be drawn on a 3D software showed extreme promise. Quickly over the years the 3D printer advanced extremely quickly in its ability to print in high quality plastics and even metals. It also improved by printing them to a very high degree of accuracy. Yet maybe the most influential and important application for 3D printing did not occur until it was brought into the world of bioengineering. Only 15 years after the first 3D printer was created, in 1999 the first human kidney was created by printing with a mix of human kidney cells and stem cells. 3D printing proved to be extremely useful in organ transplant for a plethora of reasons. For one, prior to the insertion of the newly 3D printed organ into the patient’s body, a 3D printed model of the subjects abdomen is created, so that the organ can be printed to the perfect size, shape and orientation as needed. This prevents the issue of an adult with a larger kidney not being able to donate to a child because the size of the organ. 3D printing allows the size of the organ to be printed to the exact specifications needed. Additionally, because the kidney cells are not coming from another human there is no fear of rejection. Prior to the 3D printing of organs about 17 percent of organ transplants ended in rejection, but because 3D printed organs are comprised of stem cells the printed organ practically turns into the hosts own body part and therefore there is no fear of rejection. 3D printing was around for awhile before being used in the medical community. One challenge facing 3D printing organs is that the materials used in standard 3D printers are plastics and metals. Obviously, living and nonliving biomaterials are required to properly print an organ. Again in 1999, scaffolding of a human bladder was printed by a Wake Forest lab.  Scaffolding is a 3D cluster of protein like fibers that is normally used to help regenerate tissue. The 3D printed scaffolding was then coated with cells from the patient, to reduce the chances it was rejected by the body. The cells regenerated, using the scaffolding as something to attach to and grew until they could support themselves as an organ.One specific study focused on the growing applications of scaffolding produced through a 3D printing. Scaffolding functions as an artificial extracellular matrix for patient cells to bind to.  The cells can grow once on scaffolding with them being the patient’s cells, its less likely for it to be rejected by the patient’s body. Scaffolding produced through a 3D printer is much more accurate and precise compared to models previously produced.  The materials used for scaffolding when being 3D printed are crucial for its function.Scaffolding is being used to help regenerate a type of tissue, so obviously it must be created with ingredients found in the body or similar. Some important factors to consider when determining scaffolding materials are,”biocompatibility, biodegradability, pore interconnectivity, pore size, porosity, and mechanical properties” (Do, Anh-Vu). Every patient situation is different therefore the materials used will vary.  If a scaffold is meant to degrade quickly once entered into the body it will be made out of different material than a scaffold meant to last a long time.  As cells grow and tissues form, the scaffolding will be under more and more pressure.  If not printed with the correct materials, the scaffolding could break apart, changing the initial design and possibly interfering with other cells and tissues.  “Naturally derived materials such as alginate, chitosan, collagen, fibronectin, and hyaluronic acid have an advantage over synthetic materials as they provide more innately biological functions” (Do, Anh-Vu). Using natural materials improves the chances of cells regrowing naturally on the scaffolding to produce tissues.  If the materials of the scaffolding are similar to those of the extracellular matrix then the cells will feel more natural it is very similar to what it is like in the body.  There are some synthetic polymers that mimic some natural materials like collagen.  In some cases synthetic polymers can be stronger and take longer to degrade, but the lack of biological activity in synthetic materials cause tissue regeneration leads to their occasional infectivity.With certain parts of the body require synthetic scaffolds.  One example is metals, that can be 3D printed to produce a scaffold. Specific metals like, “iron, cobalt, chromium, stainless steel and titanium alloy” (Do, Anh-Vu) can be 3D printed into scaffolding.  The advantage to printing metals is their strength.  This strength is similar to bone strength, this is a reason why bone scaffolds are commonly printed with metals.  However, 3D printing technology is still developing and not all metals can be 3d printed.  This is one of two disadvantages to 3D printing scaffolding.  The other is that metals corrode and can possible harm the body if the metals start breaking down releasing metal into the rest of the body.  Specifically, “iron-manganese (Fe-Mn) alloy was suitable for bone scaffold fabrication” (Do, Anh-Vu). Shown through studies, iron’s ability to degrade slowly overtime makes it safe to be put in the body.  Also, iron and manganese are both commonly found in the body and would be able to be broken down if released in small portions into body.Another common material used in 3D printed scaffolds, that is not natural is ceramics.  The main factors that encourage its use in the body include the fact that ceramics are very strong and do not degrade quickly.  Materials found in scaffolding like, “Hydroxyapatite (HA), itself a ceramic, is commonly found in human teeth and bones” (Do, Anh-Va).  With this commonality, a ceramic scaffolding with Hydroxyapatite could function well in bone regeneration. Similar materials and shapes allows cells to easily regenerate on the 3Dprinted scaffold. Another material commonly 3D printed ceramic is CaSiO, or Calcium silicate.  Calcium is commonly found in bones, already making it a good fit for bone scaffolding.  Not only does it have similar materials but, “pore morphology, pore size and porosity of the scaffold could be controlled” (Do, Anh-Va).  This is crucial to the functionality and regeneration of the cells.  The scaffolding need to “feel” natural to the cells in order for them to attach and grow into tissue.  If the scaffold does not mimic the extracellular matrix found in the body the cells will likely not function properly, making the scaffold ineffective. 3D printed scaffolding can include a wide range of materials, all requiring different types of 3D printers and techniques in order to produce the most accurate replication of extracellular matrix, each specific to a part of the body”You know I’m a surgeon and everyday I have to deal with my patients and the needs that they have. The best thing that we can do for our patients is to replace their defective tissues with their own tissues and that’s what this technology is all about.” (Atala) In 2008 3D printing made another great advancement in the world of bioengineering when the first 3D printed prosthetic limb was created. The limb was an arm with all the incorporated parts of a biological limb but was 3D printed as is, with no need for future assembly. 3D scanning also allows for the 3D printed limb to be scaled and incorporated perfectly onto the subjects body so that right after it is finished it can be put to use. There are countless advantages to this new form of using 3D printing to created prosthetics. For one on average a commercially produced prosthetic limb typically costs between 5,000 and 10,000 dollars while 3D printed prosthetic limbs can cost as low as only 50 dollars. Additionally, it only takes about a day to make a 3D printed prosthetic limb while it could take about 1 week to a month to produce and calibrate a normal prosthetic. 3D printed limbs also offer an amazing amount of versatility. Prosthetics made from 3D printing can be easily customized, and created to suit the owner. Artistic, rugged, and specialty designs have been made to suit specific activity use, including outdoor activities such as biking. This level of customizability would cost a fortune with current prosthetics.The last major introduction of 3D printing into the world of biomedical engineering was in 2016 when Daniel Kelly’s lab announced being able to 3D print bone, called hyperelastic bone. The main component of the hyperelastic bone is hydroxyapatite , a calcium mineral similar to that of what is found in our own bones, and two other polymers used in medicine and tissue engineering. The hyperelastic bone acts as a scaffold, that can be inserted into the body, to help regrow the patients damaged bone. It does this my encouraging new bone cells to come in and rebuild the damaged area by attaching themselves to the bone like scaffold. Because the hyperelastic bone is 3d printed it is also highly cost effective and can be printed to fit any place necessary. It is highly flexible which can allow it to be cut and reformed during surgery to ensure it can be adopted flawlessly into the patient’s body. This new and highly promising method of bone scaffolding is head and shoulders over other techniques in its field. Other scaffolds are often rejected by the bodies immune system because of the materials they are made of. Scaffolds that are made of various metals can be attacked by the immune system, which stops the bone regeneration and often leads to infection. The solution to this problem, prior to the hyperelastic bone was to use ceramic scaffolds, but these are very brittle and are difficult to insert into the body. Hyperelstic bone, solves both of these problems by being biocompatible, as well as being strong and flexible. Hyperelastic bone is the closest thing we have in the modern day to mimicking real bone inside the body. The earliest study of the 3D printer was introduced in 1984 by Charles W. Hull, more recently however, 3D printers have been able to be used in order to create bone implants for people to help support their bones or help the bones to properly heal. The earliest study of implants being 3D printed and then used is in the 1990’s with surface textures orthopedic implants made from a 3D printed ceramic shell. In this study the researchers attempted to see how viable it was to use 3D printing in order to create parts for orthopedic implants. Curodeau, Sachs, and Caldarise tested this by stress testing 3D printed implants and comparing the results against implants made by casting. What was concluded from the study was despite the precision of the 3D printed parts, the parts did not work as well as made by casting. In their publication the authors say, “The cast implants that were produced for this research were tested through standardized ASTM mechanical pull test and in vivo test on dogs. The results which are presented in Ref. 13, showed that the 3D printed texture designs had significantly greater failure stress and accelerated bone in-growth as compared to standard sintered porous surfaces.”(Curodeau, Sachs, Caldarise, 2000). This early study shows that in the beginning, 3D printed implants made with early printers were unable to handle as much force as those made by casting. During their tests they were constrained by how precise the 3D printers at the time were able to print out the implants and the materials available at the time. Despite the results showing that 3D printed implants didn’t work as well, other researchers chose to continue researching 3D printed implants and with better technology gained better results. The first successful commercially available/successful product for 3D printed implants are tooth implants. Due to their effectiveness and ease of use, dental implants have become the main treatment for replacing lost teeth or repairing damaged teeth. Through 3D printing it becomes easier to do things such as replace damaged crowns or missing teeth by using an implant. Through 3D printing replacing damaged teeth becomes much faster than in the past. Being able to 3D print new crowns and teeth make it so that a dentist can just use a digital camera to get a three dimensional model to print the new crown in minutes rather than having to wait two weeks. Normally when a patient comes in with a broken crown their dentist has to make a mold of the missing crown then spend two weeks having a replacement made but by 3D printing the amount of time gets shortened to a few hours. Three-dimensional printing makes the cost to replace a tooth cheaper through implants due to needing less time and material. More recently, from January of 2010 to January of 2012, a study was conducted using 3D printed dental implants to see how effective a 3D printed titanium implant would be. For the study the researchers used four private practices and eighty eight patients. Among the eighty eight participants there was a cumulative overall success rate of the implant working of 96.9%. With its high success rate the study was considered a success. In the publication it says, “In this 3-year follow-up prospective clinical study, single 3DP/AM implants have shown 94.5% of survival rate and 94.3% of implant-crown success rate. Considering these results, dental implants produced with 3DP/AM technologies seem to represent a successful clinical option for the rehabilitation of single-tooth gaps in both jaws, at least after a 3-year follow-up.”(Blay, Kolerman, Mijritski, Shibli, Tunchel, 2016).Early studies of 3D printing implants worked by using whatever filament was needed in the form of a powder. The powder would then be heated up and layered one by one in order to build the desired product. In a publication in the Wiley Online Library it tells how a 3D printer works. “Three-dimensional printing is a solid freeform fabrication process, which creates parts directly from a computer model. The parts are built by repetitively spreading a layer of powder and selectively joining the powder in the layer by ink-jet printing of a binder material.”(Curodeau, Sachs, Caldarise, 2000). However due to constraints of materials available and the level of technology they had, many of the 3D printed implants were not as good as those made through more traditional means such as making one from a mold.While most modern 3D printers work very similarly as those used in 1999, there are now printers that work in different ways. When printing with plastic, the object can be made by using a spool of plastic filament that gets heated up and layered. With liquid resin by using ultraviolet light, the liquid plastic solidifies and gets raised layer by layer. Now there are 3D printers that can print with organic matter, these printers work by taking cells of whatever needs to be printed and then layering them on top of each other in the desired shape. With many implants 3D printed for use today they are printed the same way as the ones printed for use in the past. However, when someone is born with defects in their bones, implants can be made from their own cells found in their bones. This works by taking a sample of cells from the patient’s bone that will be receiving the implant and then having it duplicate itself. The cells are then put into a 3D printer to print a new implant. Implants made with the patient’s own cells have a much lower risk of being rejected by their body. Often times due to being cells defective bones, other things are necessary to augment the implant. What is normally used is another implant made of synthetic materials such as calcium phosphates.Works CitedBlooms in Biomedical.” ASME.org. N.p., n.d. Web. Bergmann, Christian, et al. “3D printing of bone substitute implants using calcium phosphate and bioactive glasses.” Journal of the European Ceramic Society, Elsevier, 23 May 2010, www.sciencedirect.com/science/article/pii/S0955221910002086. Accessed 21 Sept. 2017.Curodeau, Alain, et al. “Design and Fabrication of Cast Orthopedic Implants withFreeform Surface Textures from 3-D Printed Ceramic Shell.” Wiley Online Library, 7 Sept. 2000, onlinelibrary.wiley.com/doi/10.1002/1097-4636(200009)53:5%3C525::AID-JBM12%3E3.0.CO;2-1/epdf. Accessed 21 Sept. 2017. Do, Anh-Vu, et al. “3D Printing of Scaffolds for Tissue Regeneration Applications.” Advanced Healthcare Materials, U.S. National Library of Medicine, Aug. 2015, www.ncbi.nlm.nih.gov/pmc/articles/PMC4597933/.”How 3-D Bioprinting Works.” The 3-D History of Bioprinting – How 3-D Bioprinting Works | HowStuffWorks, 17 Dec. 2013, health.howstuffworks.com/medicine/modern-technology/3-d-bioprinting1.htm. Accessed 20 Sept. 2017.Jessica BoddySep. 28, 2016 , 3:00 PM, 2017 Robert F. ServiceSep. 18, 2017 Daniel ClerySep. 15, 2017 Paul VoosenSep. 15, 2017 David MalakoffSep. 14, 2017 Sep. 19, and 2017 Sep. 18. “Print-on-demand Bone Could Quickly Mend Major Injuries.” Science | AAAS. N.p., 26 July 2017. Web. Kaplan, Saul. “My Dentist 3D Printed My Crown.” Harvard Business Review, Harvard Business, 5 Nov. 2014, hbr.org/2014/10/my-dentist-3d-printed-my-crown. Accessed 21 Sept. 2017.Kheyfets, Marianna. “Could Westworld Ever Be a Reality? This Doctor Is Already 3D Printing Tissues and Organs.” Dr. Anthony Atala Is Already 3D Printing Human Tissues and Organs. N.p., 03 Feb. 2017. Web. Murphy, Dan. “This Robot Is Learning How to Print a Human Organ.” CNBC. CNBC, 23 June 2017. Web. Tamimi, F., Torres, J., Al-Abedalla, K., Lopez-Cabarcos, E., Alkhraisat, M., Bassett, D., Gbureck, U. and Barralet, J. (2014). Osseointegration of dental implants in 3D-printed synthetic onlay grafts customized according to bone metabolic activity in recipient site.Tunchel, S., Blay, A., Kolerman, R., Mijiritsky, E. and Shibli, J. (2017). 3D Printing/Additive Manufacturing Single Titanium Dental Implants: A Prospective Multicenter Study with 3 Years of Follow-Up. NCBI.Vincent, James. “3D-printed ‘hyperelastic Bone’ Could Be the Future of Reconstructive Surgery.” The Verge. The Verge, 28 Sept. 2016. Web.

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