Note: This literature review/annotated bibliography does not imply or state endorsement of any brand or technology even where brand names exist in the literature.
This researcher first heard about 3D printers or Makerspaces in libraries. That early version of the technology reminds this researcher of Mattel’s 1960 era Creepy Crawlers Thing-Maker and Incredible Edibles toys that made toys or candy. Unbeknownst to this researcher however, major strides towards 3D printing in medicine had already occurred; starting with the field of genomics. Today, the fields of information, 3D printing, genomics, applied physics, biology, chemistry, engineering, physiology, along with research of digital technologies coalesce with the study of the body’s ability to heal itself in a new field known as Regenerative Medicine – a complex field with myriad sub complexities.
Keywords: 3D printing, regenerative medicine, additive manufacturing
Anderson, C. (2012). Makers: The New Industrial Revolution. New York, Crown Business.
Advocating the Maker Movement, Anderson explains it involves individuals integrating digital tools with physical manufacturing to produce and bring things to market while avoiding mainstream production barriers and costs thus becoming a formative pipeline that takes an inventor to entrepreneurship. Anderson goes into detail about specific technologies so that the book serves as a primer to an array of them. Cogent to the topic, Anderson elucidates the types of 3D printing, how each type works, and with what materials. His work provides easy to understand, yet foundational, information necessary to this researcher’s further study of 3D printing.
Cetrulo, K., Cetrulo, C.L., and Taghizadeh, R. R. (Eds.) (2013, February.) Perinatal stem cells. [ebook] Retrieved from Liberty University’s ProQuest eBrary.
Because stem cells figure prominently in 3D bioprinting, this researcher wants to know where they come from. This book covers a wide range of pregnancy related stem cells that are not embryonic in nature; their sources, and potential uses for them. Anzalone, Farina, Iacono, Corrao, Corsello, Zummo, and Rocca (2013) state in their chapter that obtaining these cells poses no danger to mother or child (p.77). Murphy and Atala (2013) support this finding in their chapter stating the cells come from material that is usually “discarded” after “birth” (p. 1). These authors state embryonic stem cells spawn “tumors” (Cetrulo, K., p. xv) and are therefore of no use in 3D bioprinting.
Kodicek, D. (2005, December). Mathematics and Physics for Programmers. [ebook] Retrieved from Liberty University’s ProQuest eBrary
Kodicek covers math from simple to complex always pointing to application in game programming then does the same with physics beginning with Newton’s laws. This researcher struggles with math beyond basic algebra and hopes this book will shed light on the subject in the title. What happens when a medical scientist needs to construct an organ when the original is missing? Mathematical modeling seems to be the answer. The author provides and demonstrates explanations of why and how things work mathematically making math make more sense.
Li, Y. and Luis, E. (2016). 3D printing of medical models from CT-MRI images: A practical step-by-step guide. Singapore: Partridge.
Writing for doctors and implementing open source software, the authors provide a walk-through of 3D Slicer, imaging software, and Autodesk Meshmixer, a 3D CAD (computer assisted drawing) software, with screenshots and step by step directions. This work provides the reader with a basic idea of how medical imaging and 3D printing work together. It also answers questions such as which printer to choose and how does one get a finished model where extraneous material does not appear.
3D Systems Previews D2P. (2016, November 23). 3D Systems previews D2P software solution for converting medical DICOM data to digital 3D models. 3D Systems. https://www.3dsystems.com/press-releases/3d-systems-previews-d2p-software-solution-converting-medical-dicom-data-digital-3d
The author of this article reports D2P is a new software suite expanding its “end-to-end healthcare workflow”. Whether it translates medical data into CAD or skips CAD altogether is not yet known. This software breakthrough means another step in the march towards organ bioprinting.
Bever, L. (2016, June 20). ‘We had no hope’: The amazing story of the baby born with his brain outside his skull. The Washington Post, To Your Health. https://www.washingtonpost.com/news/to-your-health/wp/2016/06/20/we-had-no-hope-the-amazing-story-of-the-baby-born-with-his-brain-outside-his-skull/
Bever (2016) reports Yoder survives a deadly “congenital birth defect” thanks, in part, to the doctors at Boston Children’s Hospital and 3D printing. Constructing models of Bentley’s skull and encephalocele, doctors “plan out and practice their maneuvers”. With this type of application, 3D printing completes the transition from mere toy to saving medical device. Bever goes on to detail the surgery and provides an update on Bentley’s progress: he can “hold up his head…eat…smile…” and even “jabber”.
Dormehl, L. (2016, August 26). 3D printing lets blind mothers ‘see’ [sic] ultrasounds of their unborn babies. Digital Trends, Cool Tech. http://www.digitaltrends.com/cool-tech/3d-printing-ultrasound/#/3
The author reports on a program that uses 3D printing technology so that “blind parents-to-be” can visualize their unborn child by making true to life models of “ultrasound images”. As of the report date, models were available to parents in Poland; parents elsewhere receive a file that can be used in conjunction with a 3D printer to print a model.
Geggel, L. (2015, March 31). Guess your age? 3D facial scan beats doctor’s exam. LiveScience. Health. http://www.livescience.com/50311-3d-facial-imaging-markers-age.html
Geggel reports on a slightly different aspect of 3D technology in medicine; the use of scanning to determine “chronological age” therefore treatment. This author mentions another brand of 3D machine; the 3dMDface. Interesting takeaway from this article: this technology is “more accurate than a physical exam”.
Groopman, J. (2014, November 24). Print thyself: how 3-D printing is revolutionizing medicine. New Yorker, Medical Dispatch. http://www.newyorker.com/magazine/2014/11/24/print-thyself
Groopman covers a wide range of applications in medicine, some that have previously been reported here going into details that others have not. Groopman also provides manufacturer names; pointing out that “Staples and Amazon” provide “3-D printing services”. Besides Amazon and Staples, Groopman mentions 3D Systems who partners with Children’s Hospital Oakland to produce a scoliosis back brace that “looks like a formfitting lace tank top”. Most notably, Groopman describes “fugitive ink” and may describe the PU from an article found earlier, more research needs to be conducted to know for sure. The authors also include a more detailed description of how researchers achieve blood vessel mimicry with endothelial cells and the “intelligence” of same as driver of new structure.
Surgeries aided by 3D. (2016). Surgeries aided by 3D medical technologies deliver hope and a new life for Rwandan teen. Stratasys, Resources, Success Stories. http://www.3dsystems.com/learning-center/case-studies/surgeries-aided-3d-medical-technologies-deliver-hope-and-new-life
The author(s) provide a look at how a medical mission, doctors in Texas, and two technologies come together to make a craniofacial repair for a patient suffering a bone disorder caused deformity. Using what was once Medical Modeling’s Solutions for Surgeons’ Virtual Surgical Planning, or VSP, and a model made with Stratasys’ ProX, doctors plan and execute the surgery leaving the patient with a symmetrical, “aesthetically correct” implant. The use of brand names gives this researcher clues for more research. This is the first medical mission related application of 3D bioprinting this researcher has come across.
Tracheomalacia in babies. (2015-2016). 3D-Airway printed splint. University of Michigan Health System, Otolaryngology-Head and Neck Surgery. https://medicine.umich.edu/dept/otolaryngology/3d-airway-printed-splint
As of this writing, five patients have FDA approved splints. This newsletter appears on the University of Michigan website as a request for donations to support research. The research involves 3D bioprinting of splints for pulmonary applications, describing three FDA emergency approvals occurring in 2012 and 2014 for skipping clinical trials to immediately implant biodegradable devices in infants or small children.
Ventola, C. L. (2014, October). Medical applications for 3D printing: current and projected uses. P&T: Pharmacy and Therapeutics. Pub Med Central. 39(10), 704-711. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189697/
Ventola covers the history of 3D printing in medicine categorizing the types of applications, types of printers, and printing systems, potentials and obstacles. Ventola becomes only the second author to discuss “unrealistic expectations”. The presence of this article and others on Pub Med Central, an open access repository of medical and science journals, along with their attendant bibliographies opens wide the door to further research. Although this researcher has already explored the legal arena, Ventola’s comments on patent and copyright law should be noted.
Scholarly (Peer reviewed) articles
Ferris, C. J., Gilmore, K. G., Wallace, G. G., & In, H. P. (2013). Biofabrication: An overview of the approaches used for printing of living cells. Applied Microbiology and Biotechnology, 97(10), 4243-58.
These authors examine the breadth of the field of 3D printing living cells by analyzing the types of printers and the various “bio-inks” (p. 4244) available; discussing advantages and disadvantages of each. Although the authors call it an overview, the depth of their research gives the reader a more detailed understanding of the overall process. The article serves as an introduction to the processes and specialized technologies necessary along with the concomitant challenges of printing with cells, for example damage caused to cells by the mechanical process of flowing through a printer head. This explains why this branch of research has not advanced as rapidly as other technologies. The authors offer brief, plain English explanations of related physiology.
Harbaugh, J. T. (2015). Do you own your 3D bioprinted body? analyzing property issues at the intersection of digital information and biology. American Journal of Law and Medicine, 41(1), 167-189.
Harbaugh’s work describes the history of the field noting the contributions of genomics adding depth to the topic while examining existing case law from conflicting angles with an eye to writing future legislation. Besides answering the question in his title, Harbaugh introduces this researcher to the relationship between bioprinting and genomics as well as the human body as data set stating, “genomics…has blurred the line between biology and digital information”. Harbaugh’s history, explanation of details, and definitions result in a fundamental building block for the topic of 3D printing.
Hsieh, F-Y. and Hsu, S-H. (2015, October-December). 3D bioprinting: a new insight into the therapeutic strategy of neural tissue regeneration. Organogenesis, 11(4), 153-158. U.S. Department of Health and Human Services, National Institutes of Health, National Center for Biotechnology Information, Pub Med Central.
In this article, the authors briefly cover preclinical animal studies using 3D printed neural stem cells or NSC’s in conjunction with a specialized hydrogel or bioink they call PU. PU is a “synthetic water-based polyurethane dispersion” or hydrogel known to “heal CNS” or central nervous system “disorders”. Two points made in this article impact the current research: first, PU “geometrically directs…repair and regeneration” and second, this article brings up the use of 3D bioprinted tissue in “drug discovery and toxicity screening”. The former answers the question, “how do the cells know what to do”; the latter is simply new information. Further, this is the only research so far to mention the use of neural stem cells.
Irvine, S. A. and Venkatraman, S. S. (2016, June 3). Bioprinting and differentiation of stem cells. Molecules, 21(9). Multidisciplinary Digital Publishing Institute. http://www.mdpi.com/1420-3049/21/9/1188
These authors give an extensive comparative analysis of bioprinting techniques and bioinks. The authors state their purpose is to use knowledge of the techniques and mediums to guide stem cell differentiation. While this body of research causes this researcher to hesitate due to its return to examination of embryonic stem cells, the authors conclude that problems with ethics and proneness to develop cancerous tumors eliminates embryonic stem cells’ viability for these applications. The embryonic stem cell issue and the bibliography leads this researcher to begin to delve into perinatal stem cells. One item of interest is the authors’ discussion of “anoikis” or cell death due to lack of “attachment” to other cells. The implications of this for the body of Christ come to mind.
Li, P. H. (2014). 3D Bioprinting technologies, patents, innovation and access. Law, Innovation and Technology, 6(2), 282-304.
Li considers existing patent laws and their potential as precedent to limit patient access to the technology. The author states she is “assessing the consequences of granting 3D bioprinting patents for access to health technologies”. What will the legal landscape for patients look like? What measures can be taken to ensure access for all? Li works on answers. Li also examines and explains early research as revealing that cells “stick together” exhibiting viscous properties so that fluid mechanics became essential. Of ethical concern: this author discusses the use of embryonic stem cells.
Si, J-W., Wang, X-D., Shen, S. G. F. (2015, January). Perinatal stem cells: a promising resource for tissue engineering of craniofacial bone. World Journal of Stem Cells. 7(1), 149-159.
The authors present a “review” (p. 150) of four types of perinatal stem cells as implemented in animal studies, only touching on cell source. Because the harvest of embryonic stem cells results in fetal death, this researcher’s Christian ethics demand knowing the outcome of harvesting perinatal stem cells before proceeding with this topic. The bibliography in this article leads to this researcher searching for and finding the book on perinatal stem cells. Back to the research at hand, craniofacial bone deformities, regardless of source, constitute some of the most disturbing medical issues or “psychomedical burdens” (p. 150).
Tung, E., Pudlo, N. (2016, December 1). On the intrinsic sterility of 3D printing. Peer J. https://peerj.com/articles/2661/
The authors’ research demonstrates fused deposition modeling, or FDM, compares to two current sterilization processes – “pasteurization” and “autoclaving”. The researchers apply 3D printed products to a growth medium called a “culture” to see what grows. Until reading the article, this researcher questions the sterility of implant and replacement material. The authors use “non-sterile polylactide (PLA) filament” from the public market place stating PLA is a “non-toxic, bio-compatible” substance “widely used in medical applications, notably “soluble medical sutures” or biodegradable stitches.
Articles not necessarily peer-reviewed
Atala, A. and Yoo, J. (2015, February 10). Bioprinting: 3D printing comes to life. ME Channels: Medical: Manufacturing Engineering Magazine. http://www.sme.org/MEMagazine/Article.aspx?id=84218
In their article, Atala and Yoo compare “printing tissues” with “engineering them by hand” covering much of the same material as other articles here with a few key additions: Wake Forest’s invention of a “hybrid [3D printing] system” and a call for others to “design” new inventions. In their “future” section and of interest to this researcher, the authors state the need to advance the technology so that “bioprinting” can occur “immediately after injury or during surgery” suggesting that “tissues can be removed and replaced during the same surgery”. These authors reveal that some bioprinting means printing “2D” forms that are “solidified” and then “combined to create 3D shapes”. In their discussion of “biomaterial,” these authors also reveal the need for a match between the rate of breakdown of biodegradable materials and the cells “building a ‘home’ from their own extracellular matrix”.
Atherton, K. D. (2015, August 24). MIT’s new 3D printer can print 10 materials simultaneously. Popular Science. http://www.popsci.com/mit-multifab-printer-prints-10-materials-simultaneously
Atherton reports on MIT’s MultiFab: a “system of systems” that can also incorporate “finished parts” in new construction. Delving into computer technology aspects, the author reveals this machine’s CPU controls everything down to reviewing imaging to adjust its print in real time. Human physiology involves a complex array of materials; blood consists of red and white cells, plasma, oxygen, and more. MIT’s new printer brings the possibility of printing of organs closer because more elements of an organ can now be printed. Notable items: MultiFab conducts and monitors visualizations of its work to adjust the print. Atherton includes a reference to the lab at MIT, CSAIL, Computer Science and Artificial Intelligence Laboratory, that produces MultiFab thus enabling the researcher to maintain contact for further developments.
Biggs, J. (2014, July 1). Researchers now able to 3D print working blood vessels. TechCrunch. https://techcrunch.com/2014/07/01/researchers-now-able-to-3d-print-working-blood-vessels/
Biggs (2014) recounts a breakthrough in medical 3D printing: the ability to print channels enabling perfusion of tissue, in other words blood flow. Cells require oxygen limiting the use of 3D printed materials. This breakthrough makes the construction of large living objects such as organs possible which means patients needing a transplant may no longer have to wait for someone else to die.
Fedorovich, N. E., Albias, J., Hinnink, W. E. Oner, F, C., Dhert, W. J.A. (2011, December). Organ printing: the future of bone regeneration? Trends in Biotechnology, 29(12), 601-606.
In this early look at 3D bioprinting, the authors discuss “regenerative medicine” as an “emerging field” limited to structures small enough for lab rats but holding promise for human use in the future. These authors discuss the use of “growth factors” such as “vascular endothelial growth factor” in the formation of the printed scaffold that will hold the living cells along with “localized gene delivery” to promote sustained cell growth in some cases or “different functionality” in others. These are the first authors to mention and consider that bone must endure pressures from “mechanical forces” that other tissue constructs do not.
Kuehn, B. M. (2016, January 26). Clinicians embrace 3D printing to solve unique clinical challenges. JAMA 315(4), 333-335.
Kuehn reports on applications of 3D printing from a medication to prosthetics as well as some applications previously mentioned in the current research. Kuehn declares prosthetics the “first [3D] medical application” to be used extensively in “clinical practice” meaning the doctor’s office or hospital. The author’s work provides another far-reaching bibliography salient to the current research. Kuehn states “organs are far more complex than anything currently manufactured and there is still much to learn about the biology and how organs work”.
ThermoFisher Scientific. (2016). Chemistry of crosslinking. ThermoFisher Scientific: https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/chemistry-crosslinking.html
This page of ThermoFisher’s website provides in depth education about the chemistry of cross linking with links out for further study of different aspects. Per the site authors, cross linking “is the process of chemically joining two or more molecules by a covalent bond”. The link and breadcrumbs at the top of the page indicate the existence of a library on this site which may be useful for further study.
Society of Manufacturing Engineering. (2016, March 28). It’s alive! Wake Forest bioprints living ear, bone, muscle. Manufacturing Engineering Magazine. http://www.sme.org/MEMagazine/Article.aspx?id=8589938793&taxid=1443
The author reports an update on research being conducted at “Wake Forest Institute for Regenerative Medicine” or “WFIRM”: namely the “ITOP or Integrated Tissue and Organ Printing System” and the successful implantation of 3D bioprinted structures in animals. The author states, “Wake Forest Baptist scientists” worked on two angles: developing and using their own bioink and printing structures with embedded “channels” for blood flow and innervation.
3D Systems. (2016). Case Studies. http://www.3dsystems.com/case-studies
This web page comes from 3D’s main website and hosts “Success Stories” as noted in the browser address bar. These case studies range from medical to non-medical applications. 3D systems provides brand names of medical grade 3D printers. The case studies feature stories of young children gaining a better life.
Carnegie Mellon University (2016). http://medrobotics.ri.cmu.edu/content/current-projects
A portal to the university’s research, this site points to several other sites including one for bioprinting; another for “plasma based materials or PBMs” that are “formable into complex 3-D shapes”; still another for projecting 3D images onto a patient during surgery. This website indicates human trials are underway.
CNET. (2016). https://www.cnet.com/
CNET serves as a news outlet for the latest in 3D technology, including medicine. CNET’s reputation as a trustworthy reviewer of technology remains. The website includes a search bar where users can search for anything including bioprinting.
CSAIL: MIT Computer Science and Artificial Intelligence Laboratory. (2016). https://www.csail.mit.edu/
This website, from the Massachusetts Institute of Technology, serves as the public face of and initial contact for the laboratory giving information about aspects of ongoing research and recent publications. Helpful features and illuminations converge as the site links to a sign up for RSS feeds of the latest publications by CSAIL researchers.
FormLabs. (2016). https://formlabs.com/
Originating at MIT FormLabs stands on its own as a spin off laboratory and business selling the Form 2 a laser printer. Concerning the current research, this printer can make models for use in medicine or be adapted to print on a ribbon as lasers do not provide a suitable environment for living tissue, yet. Form 2 represents innovations in 3D printing as the printer modifies earlier models to reduce mechanical issues such as wear on the resin basin when peeling off a layer. Form 2 also self-cleans the build area of extraneous material they call particulates and maintains a constant temperature in the resin basin meaning the object does not solidify until the scientist decides.
Medical Modeling. (2016). [December 9, 2016 redirects to 3D Systems.] Formerly Medical Modeling. http://www.medicalmodeling.com/
This site hosts Solutions for Surgeons including VSP as mentioned elsewhere in the current research. The site lists several kinds of VSP’s as well as a list of anatomical models available. Project management/software solutions exist here along with abibliography in the left-hand sidebar.
Popular Science. http://www.popsci.com/
This website is the digital version of the magazine long familiar to science and technology aficionados. Articles range from environment related to space to language to medicine. Relating to the current research, Popular Science has a Twitter account where the social media arm broadcasts latest developments, including bioprinting related articles. One major caveat: while some articles are publicly available the digital magazine comes with a subscription just like the print version.
Society of Manufacturing Engineers. http://www.sme.org/
This nonprofit supports manufacturing with peer reviewed journals, conferences: “promoting advanced manufacturing technology and developing a skilled workforce”. The site includes a search bar where other related articles may be found. SME also has a Twitter account for broadcasting the latest developments.
Stratasys, Industries, Medical. (2016). http://www.stratasys.com/industries/medical
Stratasys manufactures printers and related materials for a wide variety of industries as well as supplying educational information such as white papers. The webpage given above in this section goes to medically related information in seven categories including training, prototyping, medical devices, prosthetics, and more. This researcher finds the educational materials most interesting as well as a newsletter called the “Medical Innovation Series”. Stratasys provides “anatomical models” for medical device makers so they can demonstrate their products on the model as they try to sell their wares. Stratasys also provides “medical manufacturing” to “eliminate manufacturing constraints” something of a nod to Anderson’s revolution.
ThermoFisher Scientific. (2016). https://www.thermofisher.com/us/en/home.html
ThermoFisher’s web presence consists partly of website, trade journal, and scholarly articles. ThermoFisher provides support for science industries in the form of information, training, tools, equipment, and supplies.
ThingSmiths. (2016). http://www.thingsmiths.com/
The UM news archive holds an article mentioning ThingSmiths. ThingSmiths, located in Ann Arbor Michigan, provides professional design, scan, and print services to the public.
PubMed Central. (2016). https://www.ncbi.nlm.nih.gov/pmc/
This U.S. government website hosts science and medical journals in an open access, or free, repository. Medically related information of all types is publicly available through this portal. Like many of the other websites listed here, PubMed Central offers an avenue to stay current on this topic even after the current research is completed. The left sidebar includes a link to a journal list so that search can target one or all.
University of Michigan Health System, News. (1995-2016). http://www.uofmhealth.org/news
The website listing here lands the user on a page where users can subscribe to one or all of the UM news’ RSS feeds or read through the archive.
Wake Forest Baptist Medical Center. (2016). http://www.wakehealth.edu/News-Releases.htm
Research at Wake Forest extends beyond 3D printing but any publicly released information on their 3D research can be found here. Monitoring the site gives this researcher access to the same information at the same time as other reporters amounting to a workflow breakthrough for the researcher for the topic of 3D printing and others. Articles found here appear elsewhere in this bibliography.