Tissue Issues: The Uncharted Territory of Lab-Made Tissues

William Gay


Figure 1. Organoid: “Using Organoids for Disease Modeling: Organoid Culture Tools and Techniques.” Corning, 11 Nov. 2019, www.corning.com/worldwide/en/products/life-sciences/resources/stories/the-cutting-edge/using-organoids-for-disease-modeling.html.


Presenter's Statement: It's Not Science Fiction

What some may consider science fiction in the realm of artificial tissue creation may now, in fact, be a reality. 3D printing technology has gotten so advanced, scientists are on the road to printing organs, and they can already print bones and skin. Organoids are lab-grown entities that are produced from stem cells. They can replicate the properties of human organs, and incredible advances have been made in recent years regarding organoids. For me, what started as something that piqued my interest because it was something different and new became an elaborate maze of biological innovations that I have only begun to scratch the surface of. I found that as human tissue testing becomes more and more advanced, the ethical lines become blurred. New technologies don't have a clear "yes" or "no" answer, and the interest between scientific advancement and ethical correctness come into conflict. Both innovations go into uncharted territory in regards to medical precedents and scientific developments, and while ethicists are trying to figure out how to go about regulating and implementing these innovations in the real world, the progression of research continues. In light of this, I question: Should artificial-human-tissue development continue to progress, or should this technology be restricted?

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Figure 2. 3D-Printed Human Heart:Danova, Ina. “3D Printing Revolutionizing Medtech.” Pegus Digital, 29 Oct. 2020, pegus.digital/3d-printing-revolutionizing-medtech/.


3D Printing Human Organs/"Bioprinting"

Under this topic, I explore what 3D printing organs is, how close the technology is to the market, what technologies still need to be improved, and some concerns for the future.

Key Questions

What are the pros and cons of 3D printing organs?

  • In what ways are 3D-printed organs better? In what way are they worse?

  • Which organs are closest to being marketed to the general public?

  • Which organizations are currently on the frontlines of Bioprinting?

  • What are the ethical issues with Bioprinting?

Some Terms to Define

Figure 3. Ear Scaffold: Listek, Vanesa. “Dr. Anthony Atala Explains the Frontiers of Bioprinting for Regenerative Medicine at Wake Forest” 3DPrint.Com, 7 May 2019, 3dprint.com/242602/dr-anthony-atala-explains-the-frontiers-of-bioprinting-for-regenerative-medicine-at-wake-forest/.

Scaffolding

Scaffolding is the 3D-printed skeleton of an organ or body part on which human cells are seeded and promoted to grow.

Electrospinning

Electrospinning is a form of 3D printing in which a polymer is put in a syringe, and a spinning apparatus stretches the polymer, wrapping it around the apparatus. Electricity is used in varying amounts to direct the polymer to lay in the desired fashion, and you can see a video of this process above. This technique is used in printing the scaffolds for skin with blood vessels.

How Are Organs 3D-Printed?

This is a question with many answers. Generally, the 3D printer prints a scaffold of the organ, then it is seeded with cells from a doner. But specifically...


.

Bones: Bones are not printed to be permanent replacements, but to eventually dissolve and be replaced by the body. It is printed to hold cells and act as an environment for cells to live in and eventually overtake. You can read more by pressing the button below...

Figure 6. 3D-Printed Bone: Mensley, Matthew. “Doctors Plan to 3D Print Bone Implants Mid-Surgery.” All3DP, 30 Oct. 2017, all3dp.com/doctors-3d-print-bone-implants-mid-surgery/.


Skin: Electrospinning is sometimes used to print the scaffold for skin, and then the scaffold is populated with the skin cell layers. Further advancements in bioprinting have allowed scientists to print skin without electrospinning. Then, it is placed in an incubator to mimic the body's environment.

Figure 4. 3D-Printed Skin: Hay, Zachary. “3D Printing Skin: The Most Promising Projects.” All3DP, 7 Nov. 2019, all3dp.com/2/3d-printing-skin-the-most-promising-projects/.

Internal Organs: Internal organs have not yet been successfully printed, but components of these organs have been. Pictured below is a single, 3D-printed air sac from the lungs that has blood pumping through "vessels" on the outside of it. One challenge of printing larger organs is that the scaffold becomes difficult to populate with cells. However, the biggest challenge is to print blood vessels that can bring nutrients to every single cell while also carrying away cellular waste. Read more about specific organs below!

Figure 5. 3D-Printed Lung Air Sac: Kooser, Amanda. “Watch This Wild 3D-Printed Lung Air Sac Breathe.”, CNET, 2 May 2019, www.cnet.com/news/watch-this-wild-3d-printed-lung-air-sac-breathe/.


What Needs Does 3D Printing Organs Address? What Are the Pros?

3D Printing human organs would completely remove the need for people to wait on the organ donor list. As of September 2020, 109,000+ people are on the organ transplant waiting list, but in 2019, only 39,718 transplantations were performed. Very few organs are ever donated because only 3/1,000 people die in a way that allows for an organ donation... the donations are scarce which is why 17 people die every day waiting for an organ. With bioprinting, however, Doctors could 3D print organs using the donor's own cells and implant them with virtually no risk of the body rejecting the organ. This means that patients wouldn't have to take immune system suppressors after implantation so that the body wouldn't see the new organ as a foreign object!

Figure 7. Organ Donor Statistics: “Organ Donation Statistics.” Organ Donor, 28 Sept. 2020, www.organdonor.gov/statistics-stories/statistics.html.

What Product is Nearest to the Market?

Currently, bioprinted skin, ears, bone, corneas, and muscle are the only things that have been successfully implanted in/on animals. These are all in clinical testing. Although, no internal organs are in clinical testing.

Figure 8. ADaM's Logo: ADaM. “Additive Design and Manufacturing (ADaM).” Continental Engineering Services, 14 Oct. 2020, conti-engineering.com/highlights/additive-design-and-manufacturing-adam/.

ADaM

ADaM (Advanced Development of Additive Manufacturing) is a bioprinting organization that currently specializes in printing bones. Their prints have been given 510 (K) clearance by the FDA, meaning that the product is deemed safe to be on the market. Their 3D-printed bones can be expected to be on the market in as little as one-and-a-half years! The way the bone works is, once implanted, the body will slowly grow new bone to replace it. The implant doesn't replace bone, it just acts as a durable placeholder. ADaM's long-term plan is to go beyond bones and venture into the world of printing affordable organs and tissues for market.

Rensselaer Polytechnic Institute


The Rensselaer Polytechnic Institute also wishes to 3D print a body part to put on the open market, but it isn't bone... it is skin. They are going beyond skin patches, and they are trying to 3D print skin grafts. The difference is that grafts have blood vessels that can combine with the pre-existing vessels in the wound, while patches just cover wounds to prevent infection. The skin grafts have worked in testing. Their long-term goal is to make personalized grafts that have little to no risk of being rejected by the patient’s body.

Figure 9. Bioprinter Extruder: Wells, Torie. “Living Skin Can Now Be 3D-Printed With Blood Vessels Included.” Rensselaer, 1 Nov. 2019, news.rpi.edu/content/2019/11/01/living-skin-can-now-be-3d-printed-blood-vessels-included.

Figure 10. 3D Rendered Skin Vasculature: Rensselaer Polytechnic Instititute. “Rensselaer Team 3D Prints Skin with Blood Vessels Included.” YouTube, 1 Nov. 2019, www.youtube.com/watch?v=7uM9HDmBeVE.



Key Facts to Consider:

  • The Organ Donation list has over 109,000 people on it, and only 39,718 organ transplants were performed last year.

  • Through creating custom organs, scientists are mitigating the risk of the patients' bodies rejecting the organs.

  • 3D-printed organs will be monetized.

  • 3D-printed organs can be modified to improve function and possibly prolong life (in the future).

  • There is no legal definition for what a 3D-printed organ is.

Ethical Issues with 3D Printing Organs

As 3D printing progresses, one concern that is emerging is what will eventually become available for anyone to use. In a decade, or even a few years, technology on the cutting edge today will become obsolete, and that technology will be available to anyone who wants to use it.


Through the process of exploring and creating organs, 3D printers may be able to modify organs or body parts to either unnaturally prolong life or to make someone more efficient and durable in battle.


Another argument is that 3D printing an organ is simply going too far… we shouldn’t be infringing on the natural process of organ formation.


Animal testing is a major component of 3D printing organs. Scientists are nervous to transfer to testing on humans, but they disregard the fact that animals deserve similar or the same moral status. (See Janaki's presentation on animal product testing)


3D-printed organs don't have a legal definition... They aren't organs because they were never born alive, and they aren't drugs because they can't be taken orally and/or they don't relieve a specific illness. This leads to the concern of whether or not progress on bioprinting technology should stop until these "organs" have a legal definition thus defining the limits of experimentation.


3D-printed organs aren't one-size-fits-all... They are personalized to the patient using their own cells, meaning that experimentation cannot be done on a large scale like how drug testing is done; it will have to be on an individual level with individual results.


The last argument that I feel is important to share is that 3D-printed organs would be monetized. This brings the concern that they will only be for the wealthy, and the lower classes would be resigned to wait on the organ donation waiting list. The same thing could happen if this technology is headed, distributed, and or used by private companies seeking profit.


*Although there are so many ethical issues with 3D printing organs, that is the case with many cutting edge technologies involving humans. I urge you to not just look at the number of issues, but the actual content of each one. Also, compare it to the above topic about what issues 3D printing organs addresses and weigh them against each other.*

Stakeholders

  • The organ printing companies

  • The lower-income people who can’t afford the organs

  • The higher-income people who can afford the organs

  • Scientists

  • The Military

  • The general public regarding safety

  • Everyone on the Organ donation waiting list

  • Animal test subjects

Ethical Principles to Consider

Beneficence: Beneficence is to bring about good in all of your actions. With 3D printing organs, the waiting list would be cut down significantly, and the risk of the patient's body rejecting the organ is nearly 0. Also under beneficence is the concern that the technology is getting too advanced, and we must slow down advancement before this technology becomes available to the public.


Non-Maleficence: Non-Maleficence is to do no harm. Here, animal testing, future human testing, and the use of bioprinted organs to artificially enhance the human body for combat should be considered. All of these either have the potential to or will do harm, so the question is: using the principle of non-maleficence, does the possible good that bioprinting organs could bring about outweigh the risks involved in the process of experimentation or the possible military use of modified body parts?


Justice: Justice is to provide others with what they deserve or what they are owed. The monetization and privatization of these organs could lead to bioprinted organs only being for the well-off, excluding the people who can't afford them. Currently, organ donations are free, so is this technology just bringing money into somewhere it doesn’t belong?

Figure 11. Liver Organoid: “Organoid Research.” STEMCELL Technologies, www.stemcell.com/technical-resources/area-of-interest/organoid-research.html.



Organoids and Gastruloids

Under Organoids and Gastruloids, I am going to explore what they are, how they are used, what the future plans for them are, and what the ethical concerns about the future of Organoids and Gastruloids are.

Key Questions

  • How Do Organoids and Gastruloids differ from human embryos?

  • What is the moral status of organoids and gastruloids?

  • How can organoids and gastruloids progress? How far have they progressed already?

  • What is being done with organoids and gastruloids?

  • What are the ethical issues with organoids and gastruloids?

Some Terms to Define:

Figure 12. Cerebral Organoid: “Brain Organoids 'Made in Austria' Resemble Original to a Great Extent.” Austrian Academy of Sciences, 20 Dec. 2016, www.imba.oeaw.ac.at/research-highlights/brain-organoids-made-in-austria-resemble-original-to-a-great-extent/.

Organoids

An Organoid is a collection of artificially configured, specialized cells derived from stem cells. They can be specialized to be organ cells. These are the more ethically-sound alternatives to using animal embryos in research.

Figure 13. Group of Gastruloids: “Gastruloids, Neuronal, and Cerebral Organoids.” The Liberali Lab, liberalilab.org/projects.

Gastruloids

Gastruloids are the product of stem cells beginning in the blastocyst stage that have undergone gastrulation. Gastrulation is the process that the embryonic cells undergo to go from a random amalgamation of human cells to an organized outline of the embryo. However, there are some critical differences between the gastruloids’ process and a gastrula’s (the naturally-forming organisms that develop in the uterus) process of gastrulation: gastruloids lack the potential to form a yolk sac/placenta and brain tissues...

Figure 14. Biobank: Sim, Jolene. “The Difference Between Biobanks and Biorepositories.” Biorepository, 10 Nov. 2018, www.geneticistinc.com/blog/the-difference-between-biobanks-and-biorepositories.

Biobanking

Biobanking is the collecting and storing of various tissue samples that are used for experimentation or implantation. It is how organoids and gastruloids are stored and preserved.

Figure 15. Stem Cell Specialization Process: “Stem Cells for Joint Pain.” Foothills Orthopedic & Sport Therapy, 20 Jan. 2020, www.foothillstherapy.com/2020/01/20/stem-cells-for-joint-pain/.

Stem Cells

Stem Cells are non-specialized cells that can be specialized to be any cell in the body. There are different types of stem cells: embryonic stem cells which come from 3-to-5-day-old embryos, non-embryonic stem cells which come from already-developed organs, induced pluripotent stem cells (iPSC) which are reprogrammed, adult stem cells that are de-specialized to be made into any tissue, and cord blood stem cells which are taken from the umbilical cord.

Figure 16. The process of IVF: Lane, Danielle. “The Beginner's Guide to In Vitro Fertilization (IVF).” Lane Fertility Institute: Fertility Specialists, www.lanefertilityinstitute.com/blog/ivf-in-vitro-fertilization

In Vitro Fertilization (IVF)

In Vitro Fertilization is the fertilization of an egg in a lab setting (literally meaning "in glass").

Figure 17. Ultrasound: “Ultrasound.” Wikipedia, 20 Oct. 2020, en.wikipedia.org/wiki/Ultrasound.


In Vivo

In Vivo means to be in a living organism (ie. an in vivo embryo).

Uses of Organoids and Gastruloids

Currently, Organoids and Gastruloids have 4 main uses which are:

Some scientists are using them to learn how the body works and how it develops:

Organoids are perfect for studying the early stages of embryonic development that were previously impossible to study. One scientist, Karla Kim, Ph.D., works with stem cells to find how they regenerate and function. Her lab is currently working with IPSCs which she takes from skin and blood samples to create lung organoids and study the development of lung diseases in the embryonic state. Hongjun Song and Guo-li Ming have figured out how the Zika virus affects embryos through infecting a brain organoid with the virus and studying the effects. Other experiments include figuring out what environment is necessary for stem cells to specialize in certain ways, and how other organs, specifically the brain, form. Cerebral organoids (brain organoids) are used to study neurological conditions like autism and schizophrenia. Gastruloids are used to study the complex process of gastrulation as well as several heart diseases stemming from disturbing an embryo in this state. Because of gastruloids, scientists can study exactly what disturbances cause these heart diseases without the need to experiment on animal embryos. Gastruloids are vital in learning about development because experimentation performed on human embryos is limited to 14 days.

Some scientists use them to figure out how to treat diseases and conditions:

Organoids can also be used to see how to reverse chronic brain, organ, or bodily diseases. For example. David Breault and Qiao Zhou used intestinal organoids to turn them into insulin-producing beta cells for people with diabetes. Tests have been conducted on animals, and they worked! Scientists are also using cerebral organoids to trace back the origins of schizophrenia and autism. From here, they can find ways to prevent these conditions. When I read this, a massive red flag went up in my head because this sounds like it is approaching eugenics. Could the treatment of neurological diseases cross the line of trying to perfect humans and eliminate “flaws”?

Organoids can be used to test new medicines:

In the past, medicines have been tested on animals, but have a bright future in testing medicines. The benefit of using organoids is that they isolate a specific type of cell, thus experiments can be done to see how each individual organ reacts to the medicine. In addition, the tests would be more accurate and humane, and the results would be more immediate than in animal testing.

Organoids can benefit people with rare medical conditions:

Samples can be taken from a patient with a rare condition, then tissues can be grown from that sample and stored. That way, the person wouldn't need a donor with the same condition, they have their own cells stored and ready to go! Connected with the previous point, organoids grown from people with these rare conditions could be used to figure out how to treat them... scientists would never even have to perform tests on that individual.

Figure 18. Stages of Fetal Development: “Things You Need to Know About Embryo Development Stages After IVF.” OVO Health, 11 July 2019

Figure 19: Baby Affected by the Zika Virus: Vogel, Gretchen. “Zika Virus Kills Developing Brain Cells.” Science, 4 Mar. 2016, www.sciencemag.org/news/2016/03/zika-virus-kills-developing-brain-cells.

Figure 20: Neural Cells: “Neurological Disorders.” Rehab Advantage & Sports Medicine, 19 Nov. 2020, rehabadvantagesportsmed.com/physical-therapy-services/neurological-disorders/.

Figure 22: Vaccine: Polakovic, Gary. “Coronavirus Vaccines Are Coming, But When Will They Arrive?” USC News, 25 June 2020, news.usc.edu/172028/coronavirus-vaccine-covid-19-development-approval-usc-experts/.

Figure 23: Organized Cerebral Cells: Weiler, Nicholas. “Not 'Brains in a Dish': Cerebral Organoids Flunk Comparison to Developing Nervous System.” USCF, 29 Jan. 2020

Figure 24: Disorganized Cerebral Cells: Weiler, Nicholas. “Not 'Brains in a Dish': Cerebral Organoids Flunk Comparison to Developing Nervous System.” USCF, 29 Jan. 2020

The Current Challenges and Progress of Organoids and Gastruloids


Currently, organoids are hard to control. In lab settings, they experience a lot of "cellular stress" which results in the cells specializing in random ways. For example, cerebral organoids will develop normally, but suddenly, the stem cells will begin to fall into disarray, leading to a collection of disorganized cells. To go around this issue, scientists have implanted cerebral organoids in mice, and their stress levels fell. This isn't a permanent fix, and they will have to figure out a way to reduce cellular stress in vitro. Although, in general, functioning tissues of multiple different organs have been produced. Gastruloids have had a little more success, and their behavior is predicted more easily. However, much more research must go into both of these before they can be considered consistent.

Limitations on Experimentation

Currently, there are some limitations on experimentation with cerebral organoids. Because they are so new and there isn't any precedence, limits from similar places of stem cell research must be put on them to ensure ethical experimentation. Cerebral organoids have been governed by the "14-day rule" which was developed in the 1970s by the Warnock Committee to prevent unethical experimentation on in vitro embryos. The limit is 14 days because soon after this, the embryo will undergo gastrulation and develop neural cells thus giving it moral standing due to its ability to feel pain. By ONE definition of moral standing (the entity has the desire to avoid pain or experience pleasure), early human embryos (before 14 days) don't have moral standing, but they do have moral potential because they can develop these attributes. However, this is not a fitting limitation on cerebral organoids because they skip steps in natural development, and they don't follow the same timetable as an embryo. To find the limits of testing, their moral status must be examined.


One argument is that cerebral organoids have moral standing because they are of human origin, thus they should be governed by the 14-day rule or something similar. To counter that, one could argue that it is instead of lab origin because it is modified and grown unnaturally. Another possible route would be to somehow test for an organoid's ability to grow and self-develop. This method would show whether the organoid was just a mass of cells or if it was something more complex that is worthy of moral recognition, but the test for this would be difficult to determine. Something that is commonly considered in determining the moral status of these organoids is whether or not they can feel pain. If it can, it falls under the decision that the Warnock Committee came to. Something else that must be considered is that, religious beliefs aside, the brain is what makes people who they are. If a brain were to be transplanted from one person to another, that brain wouldn't take on the personality of the person it is transplanted into because it has totally different neural connections. Because cerebral organoids are neural cells, and thus they technically have the potential to function and make the connections that make us human, should they get the same moral consideration as early embryos? Should scientists be able to experiment on these if they have the potential to develop pain receptors? Also, is it ethically sound to place all of the moral considerations in the organoid's ability to feel pain? What if a brain is grown in vitro that has the ability to function, but it has been modified to not feel pain? All of these questions must be considered when deciding the ethical limits on organoid experimentation.

Key Facts to Consider

  • Organoids and gastruloids use stem cell technology.

  • Organoids and gastruloids are currently being used to figure out how to treat diseases and where neurological diseases come from.

  • Organoids, especially cerebral organoids, don't have a set-in-stone guideline for experimentation.

  • Although organoids and gastruloids use animal experimentation, they are also working to prevent the need for animal experimentation in medicines and treatments of diseases.

  • Organoids and gastruloids can be extremely beneficial to those with rare medical conditions.

The Ethical Issues With Organoids and Gastruloids

One argument against organoids is that people dislike that stem cells are used... they believe that stem cells shouldn't be messed with or that it is unethical to use them, especially those from early embryos.


An argument against the creation of cerebral organoids is that they have the potential to create neural connections, thus leading to concern about their moral standing.


As research progresses, it becomes more and more evident that new definitions of what is ethical within these experiments are necessary… however, there is no precedence. Something that I worry about is, historically, when there is no precedence, experiments push the boundaries of human rights or what is humane. Should we approach the progression of organoids more carefully to ensure that we don’t get ahead of ourselves and end up violating moral and ethical principles?


Organoids are going to be studied to see how certain brain disorders develop… However, this would include autism, down syndrome, and other lower-risk, neurological conditions. If they study these and attempt to cure them, could this lead humanity down the path of eugenics?


Biobanking is another concern because it is unclear how private or public organoid biobanks should be.


Privacy is another ethical concern. Donors must have complete informed consent when donating their tissues because the cells can be traced back to them. Organoids can be de-identified, a process that removes any personal information that makes the cells traceable back to the donor, but the scientific value decreases significantly when this is done... preferably, the cells should retain the individual genetic material. (For more information on de-identifying biological material, go HERE)


If/when this technology is advanced enough to go into clinical testing, a few problems arise from this. First, trials will be very invasive, and the scientists will need to know as much as possible about the patient's body to reduce the risks and maximize the scientific value. Second, there is no way to do mass testing, it is all on an individual level (like bioprinting). This means that what works for one patient might be completely different than what works for another patient. Finally, the question of who would get the treatment arises. This technology is intended to be most beneficial to children, but is it ethically sound to perform these invasive experiments on children? Also, if clinical studies are only performed on adults, how will we know what treatment works for children?


The definition I used for moral value is only one of many interpretations. One person may view moral value as the definition I gave, but someone else might have a different definition that dictates how they view experimentation with organoids and gastruloids. If most people use a different definition and view organoids as morally and ethically unsound, what good is this technology? Why continue to progress with these experiments?

Stakeholders

  • Human Embryos (Through Modification)

  • People with neurological differences

  • Scientists

  • Cerebral organoids (If they become advanced enough)

  • Animal test subjects

Ethical Principles to Consider

Beneficence: Beneficence is both to bring about good in all of your actions, or to bring about good for the most people. In this case, organoids have the potential to help thousands or millions by treating diseases and helping people with rare conditions. In addition, they can give us invaluable information about how organs and embryos develop. However, does all of this outweigh the future risks, human testing, and the waiving of privacy?


Nonmaleficence: We must first do no harm. This is similar to the downside of beneficence where the future risks, human testing, and waiving privacy may do more harm than good in the long run.

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Annotated Bibliography (Click Dropdown to View)

Arias, Alfonso Martinez. “Background to Human Gastruloids.” Martinez Arias Lab, 11 June 2020, amapress.gen.cam.ac.uk/? page_id=2478.

This Article briefly talks about the Warnock Report and why we can’t study embryos past 14 days. It also gave me key information on what differentiates gastruloids from gastrula.


Boers, Sarah N, et al. “Organoid Biobanking: Identifying the Ethics.” EMBO Reports, John Wiley & Sons, Ltd, 13 June 2016, www.embopress.org/doi/full/10.15252/embr.201642613.

This Source discussed some ethical concerns with organoids and gastruloids, specifically Biobanking, Consent, and how clinical studies should work.



Everett, Hayley. “A.D.A.M. Receives 510 (K) Eligibility from FDA for 3D Printed Bones.” 3D Printing Industry, 22 Oct. 2020, 3dprintingindustry.com/news/a-d-a-m-receives-510-k-eligibility-from-fda-for-3d-printed-bones-177805/.

A.D.A.M.(Advanced Development of Additive Manufacturing) has gotten 510 (K) clearance from the FDA which means that the product is safe enough to market. They plan on bringing 3D printed bones to market, and they have a long-term strategy of 3D printing other tissues on demand. The CEO of A.D.A.M. says “Our plan is to go beyond bones and allow people to have their tissues and organs printed for an affordable cost, when and where they need them”.



Giges, Nancy. “3D Printing Living Skin with Blood Vessels.” ASME, 22 Jan. 2020, www.asme.org/topics-resources/content/3d-printing- living-skin-with-blood-vessels.

This article talks about one lab’s method to grow skin. It says that they print in blood vessels that have been successful in animal testing making it more than just a skin patch but rather a temporary skin graft.



Hooper, Olivia. “Five Ethical Concerns with 3D Printing in Medicine.” Law Technology Today, 26 May 2020, www.lawtechnologytoday.org/2020/05/five-ethical-concerns-with-3d-printing-in-medicine/.

This article expressed some concerns of 3D printing organs. They said that, if left in the hands of private companies, they could price the organs too high. Also, organs have to be specialized, they can’t be clinically tested in mass amounts, so each individual test result may be different. One more concern is that organs will be modified to become more efficient thus lengthening our lifespans or making us “inhuman”.



Hostiuc, Sorin, et al. “The Moral Status of Cerebral Organoids.” Regenerative Therapy, Japanese Society for Regenerative Medicine, 15 Mar. 2019, www.ncbi.nlm.nih.gov/pmc/articles/PMC6423994/.

Summary: This article covered a lot, but the meat of the article was discussing the moral standing of gastruloids and organoids. It discussed how, currently, organoids and gastruloids are held to the standards of human embryos, but they aught to have different standards because they are so different. The article shows how the true definition of a human is their brain because you can remove and replace everything in a human, but if you replace the brain, they aren’t the same person. Thus, cerebral organoids should be carefully monitored to ensure that functional brains arent grown in a tube. The article also says that although stem cells technically have a moral standing because they are derived from humans, their standing doesn’t outweigh the possible good of finding cures to diseases.



Kelly, Cassie. “3D-Printed Organs Nearing Clinical Trials.” ASME, 3 Mar. 2020, www.asme.org/topics-resources/content/3d-printed- organs-nearing-clinical-trials.

This article talked about the process of 3D printing organs and seeding the organ scaffold with cells. It also discusses the main issue with 3D printed organs: creating a system that will bring oxygen and nutrients to the cells while also carrying away cellular waste.



Kunwar, Damini. “The Uncertainty of Regulating 3D Organ Printing.” The Regulatory Review, 28 Dec. 2019, www.theregreview.org/2019/12/10/kunwar-uncertainty-regulating-3d-organ-printing/.

This article describes the possible dangers and/or ethical issues of 3D printed organs. It says that the printers require stem cell technology and that 3D printing may open up possibilities in the military making people less vulnerable to injuries. Also, they can’t be classified as organ or drugs, so they have to have a brand new category.



Madsen, Pete. “Moral Standing.” Encyclopædia Britannica, Encyclopædia Britannica, Inc., www.britannica.com/topic/moral- standing.

This article defines moral status as seeing if the well-being of an entity should be considered and if the entity has its own interests to avoid pain or experience pleasure.



“Organ Donation Statistics.” Organ Donor, 28 Sept. 2020, www.organdonor.gov/statistics-stories/statistics.html.

This article was about organ donor statistics. The ones that struck me were that 109,000+ people were on the waiting list, but 39,718 transplants were performed in 2019; Only 3/1,000 people die in a way that allows for an organ donation, 17 people die everyday waiting for an organ transplant, and in 2019, over 90,000 people needed kidney transplants, but just over 20,000 donations were received.



“Organoids: A New Window into Disease, Development and Discovery.” Harvard Stem Cell Institute (HSCI), 7 Nov. 2017, hsci.harvard.edu/organoids.

This Article goes in depth about what organoids are. They are a small collection of cells between the size of being thinner than the width of a hair-5mm. Scientists take a group of stem cells and put them in the environment necessary for them to specialize, and they can create small portions of organs. Organoids are being used in 3 different ways: Some scientists use them to figure out how fetal organs develop, some are using them to test how medical treatments of diseases and illnesses will affect certain tissues, and some are using them to learn how to treat terminal illnesses like diabetes.



Royal Society of Biology. “From Organoids to Gastruloids.” RSB, 2013-2020, www.rsb.org.uk/links/158-biologist/features/1830-from- organoids-to-gastruloids.

This article was a little older, so I used a more up-to-date article about the progress of organoids, but this still article still had important information. It defined gastruloids as a group of cells that begins in an artificial blastocyst stage, and it undergoes gastrulation… they are also more reliable than organoids because they can be consistently reproduced. Also, they can form nodes which is an important thing to study in human development. The article also brought to light that the embryonic structures could begin to create “a structure that has neuralated” meaning it would be sentient.



Weiler, Nicholas. “Not 'Brains in a Dish': Cerebral Organoids Flunk Comparison to Developing Nervous System.” USCF, 29 Jan. 2020, www.ucsf.edu/news/2020/01/416526/not-brains-dish-cerebral-organoids-flunk-comparison-developing-nervous-system.

This article discusses the progress of cerebral organoids and defines them. Cerebral organoids are balls of brain-like issues grown in a lab using stem cells, and they are/will be used to study brain development. However, progress on them aren’t as far along as it is advertised. Once they begin growing, the cerebral organoids quickly devolve into a mixed-bag of cell types… they aren’t specializing properly. It was found that the main reason for this is the cellular stress in a laboratory environment which was fixed when the organoids were implanted into a mouse’s brain. However, lab settings have not yet reached a point in which cerebral organoids can be successfully grown.



Yasinski, Emma. “On the Road to 3-D Printed Organs.” The Scientist Magazine®, 26 Feb. 2020, www.the-scientist.com/news- opinion/on-the-road-to-3-d-printed-organs-67187.

This article discusses the progress of 3D printing organs. Thus far, no actual organs have been 3D printed, but some tissues have been 3D printed. Currently, 3D printed ears have been implanted, and 3D printed corneas, ears, skin, and bones are in clinical testing.



“3D Printed Bones.” ADAM, adamproject.org/.

A.D.A.M. Is a 3D printing company focused on 3D printing bones and organs. Their bones will dissolve over time being replaced by new bone growth. They have a mission to create human bones and organs on demand because 150,000 people have died in the organ donation list in the past 20 years.

Works Cited (Click Dropdown to View)

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“Brain Organoids 'Made in Austria' Resemble Original to a Great Extent.” Austrian Academy of Sciences, 20 Dec. 2016, www.imba.oeaw.ac.at/research-highlights/brain-organoids-made-in-austria-resemble-original-to-a-great-extent/.

Danova, Ina. “3D Printing Revolutionizing Medtech.” Pegus Digital, 29 Oct. 2020, pegus.digital/3d-printing-revolutionizing-medtech/.

“Gastruloids, Neuronal, and Cerebral Organoids.” The Liberali Lab, liberalilab.org/projects.

Hay, Zachary. “3D Printing Skin: The Most Promising Projects.” All3DP, 7 Nov. 2019, all3dp.com/2/3d-printing-skin-the-most-promising- projects/.

Kooser, Amanda. “Watch This Wild 3D-Printed Lung Air Sac Breathe.”, CNET, 2 May 2019, www.cnet.com/news/watch-this-wild-3d- printed-lung-air-sac-breathe/.

Lane, Danielle. “The Beginner's Guide to In Vitro Fertilization (IVF).” Lane Fertility Institute: Fertility Specialists, www.lanefertilityinstitute.com/blog/ivf-in-vitro-fertilization.


Listek, Vanesa. “Dr. Anthony Atala Explains the Frontiers of Bioprinting for Regenerative Medicine at Wake Forest” 3DPrint.Com, 7 May 2019, 3dprint.com/242602/dr-anthony-atala-explains-the-frontiers-of-bioprinting-for-regenerative-medicine-at-wake-forest/.

Mensley, Matthew. “Doctors Plan to 3D Print Bone Implants Mid-Surgery.” All3DP, 30 Oct. 2017, all3dp.com/doctors-3d-print-bone- implants-mid-surgery/.

“Neurological Disorders.” Rehab Advantage & Sports Medicine, 19 Nov. 2020, rehabadvantagesportsmed.com/physical-therapy- services/neurological-disorders/.

“Organ Donation Statistics.” Organ Donor, 28 Sept. 2020, www.organdonor.gov/statistics-stories/statistics.html.

“Organoid Research.” STEMCELL Technologies, www.stemcell.com/technical-resources/area-of-interest/organoid-research.html.

Polakovic, Gary. “Coronavirus Vaccines Are Coming, But When Will They Arrive?” USC News, 25 June 2020, news.usc.edu/172028/coronavirus-vaccine-covid-19-development-approval-usc-experts/.

Rensselaer Polytechnic Instititute. “Rensselaer Team 3D Prints Skin with Blood Vessels Included.” YouTube, 1 Nov. 2019, www.youtube.com/watch?v=7uM9HDmBeVE.

Sim, Jolene. “The Difference Between Biobanks and Biorepositories.” Biorepository, 10 Nov. 2018, www.geneticistinc.com/blog/the- difference-between-biobanks-and-biorepositories.

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“Things You Need to Know About Embryo Development Stages After IVF.” OVO Health, 11 July 2019, www.ovohealth.com/fertility/blog/pregnancy/embryo-development-stages.

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“Using Organoids for Disease Modeling: Organoid Culture Tools and Techniques.” Corning, 11 Nov. 2019, www.corning.com/worldwide/en/products/life-sciences/resources/stories/the-cutting-edge/using-organoids-for-disease- modeling.html.

Vogel, Gretchen. “Zika Virus Kills Developing Brain Cells.” Science, 4 Mar. 2016, www.sciencemag.org/news/2016/03/zika-virus-kills- developing-brain-cells.

Weiler, Nicholas. “Not 'Brains in a Dish': Cerebral Organoids Flunk Comparison to Developing Nervous System.” USCF, 29 Jan. 2020, www.ucsf.edu/news/2020/01/416526/not-brains-dish-cerebral-organoids-flunk-comparison-developing-nervous-system

Wells, Torie. “Living Skin Can Now Be 3D-Printed With Blood Vessels Included.” Rensselaer, 1 Nov. 2019, news.rpi.edu/content/2019/11/01/living-skin-can-now-be-3d-printed-blood-vessels-included.