By Connor Tsuchida, Annapurni Sriram, Brianna McIntosh, Erin Inchinotsubo, Alexander Novokhodko
Entering the Third Dimension
What desperate patients currently wait months to years for, could soon be made in days. What use to be adapted for the body, can now be made of the body. Aside from prototyping and manufacturing, 3D printing, has found its niche in biotechnology and medicine. Whether printed to enhance, support, or replace components of the human anatomy, 3D printing has brought medicine to a place once reserved for science fiction.
The history of 3D printing is as rapid as the manufacturing process itself. In just three decades, the technology has evolved from layering plastic prototypes to printing functioning organs, capturing the imagination of hobbyists and medical researchers alike.
In 1986, U.S. Patent 4575330 was issued to Charles Hull for “An Apparatus for Production of Three-Dimensional Objects for Stereolithography” . Hull’s first printer utilized photopolymers: materials that transform from a liquid to a solid under UV light . In a vat of liquid photopolymer, Hull’s machine laser cured two-dimensional cross sections from liquid to solid, layering the sections to create a three-dimensional object.
Just five years later, Scott Crump and his company Stratasys developed fused deposition modeling (FDM), a now equally popular method for 3D printing . FDM works like a traditional hot glue gun, but replace the operator’s hand with a precise computer and the arts and crafts for solid three-dimensional objects. Rather than using UV light to cure material in layers like stereolithography, FDM heats thermoplastics to a semi-liquid state and extrudes a two-dimensional cross section onto a stage. The printer then continues this process, adding layer upon layer of quickly curing thermoplastic until the object is created.
FDM, along with stereolithography, was envisioned to revolutionize the manufacturing industry, not the biomedical field. Pioneers foresaw their machines replacing manufacturing lines, not saving lives. Even Charles Hull, when asked what surprised him most about his invention, said: “To me, some of the medical applications. I didn’t anticipate that... ” . Still, much to the surprise of 3D printing pioneers, biomedical researchers have adapted 3D printing to solve some of medicine’s largest problems.
Recreating Lost Parts
Leopard geckos grow back whole tails and zebrafish can regenerate massive portions of a damaged heart, yet compared to the rest of the animal kingdom, humans poorly regenerate. While broken bones and cuts heal, lost limbs or failing organs are gone for good. Worst-case scenario: the organ is vital and death is imminent. This is the case for the 122,000 people nationally who are currently waiting for organ donations as their vital organs fail . Best-case scenario: the loss of limb or organ only reduces the victim’s quality of life.
This is the case for the 1.7 million people living with limb loss in the United States alone . Either scenario, the piece of human anatomy is gone forever without any chance of growing back to restore function... at least not naturally.
A possible solution to these problems lies at the intersection of 3D printing and medicine. Rather than printing airplane parts, biomedical engineers sought to print prosthetics, implants, tissues, and even functioning organs. While huge limitations in the regenerative abilities of the human anatomy challenge medical scientists today, 3D printing presents an enthralling possible solution.
Printing for the Body
3D printing is revolutionizing the way that biotechnology interfaces with the human body. While much of the human anatomy does not regenerate, researchers and engineers have tapped into the seemingly endless potential of 3D printing to create replacements for failing human anatomy.
While not living tissue, these replacement parts offer similar structure and function to greatly enhance quality of life. From prosthetics to surgical implants, 3D printing is ushering in a new realm of cost-effective, individualized, and innovative healthcare solutions. In the case of Draje Josevski, an Australian man suffering from an advanced case of chordoma (a rare spinal cancer), 3D printed
titanium vertebrae were a second chance at life . Chordoma left his spine riddled with malignant tumors and showed no signs of stopping – without new vertebrae his prognosis was poor.
Still, medical pioneer Dr. Ralph Mobbs was able to implant custom titanium printed vertebrae to replace the cancer-riddled spine. The surgery to implant the 3D printed vertebrae – the first of its kind – took 15 hours and required Dr. Mobbs to detach Josevski’s head from his neck, implant the printed vertebrae, and then reattach the head and neck. The successful surgery and new vertebrae allowed Josevski to live a normal cancer-free life.
Similarly, another first-of-its-kind surgery at the University Medical Center (UMC) in Utrecht, Netherlands successfully saved a life by utilizing rapid and customizable 3D printing .
A young women with Van Buchem Disease, a fatal disease where a thickening skull significantly impacts brain function, was brought to UMC Utrecht after experiencing vision loss . To treat her, Dr. Bon Verweij and Dr. Marvick Muradin successfully replaced the patient's abnormal skull with a 3D printed model in a 23-hour surgery. After the 3D printed skull was implanted the patient was able to gain normalcy in her life, and even miraculously regained her vision.
In addition to 3D printed surgical implants helping people from within the body, 3D printed prosthetics is a burgeoning field within medicine that utilizes 3D printing to replace outer portions of the body.
Open Bionics, an English startup company, is equipping hand amputees with comfortable prostheses. The prostheses look very similar to hands and use myoelectric sensors to allow the wearer to control the prosthetic. The customizability that comes with 3D printing is extremely important in creating individualized prosthetics for people of all shapes and sizes.
In addition, these 3D printed prostheses offer a more affordable option to conventional prostheses: the Open Bionics hand prosthetic cost around $2,900 compared to the conventional prosthetic cost of around $50,000 .
Printing THE Body
While plastic or metal replacements can save and enhance lives, the question lingers: can we do better?
The fundamental components of the human body are cells, which layer to form tissues. Rather than plastic or metal replacements, researchers sought to make cellular replacements. Using living cells, researchers hoped to create replacement anatomy as close to the original biological structure as possible. The basic strategy involves 3D printing a scaffold to assist with cell growth. Much like how vines require a wall to grow up, cells require a solid structure to grow into and around. By 3D printing this scaffold structure in the desired geometry, and then covering this with cells, a customized tissue can be grown.
Scientists at the Wake Forest Research Institute in North Carolina have used these techniques in human trials . The team 3D printed an artificial biological bladder for actual human cells. Cells from the patient’s failing bladder were removed and placed on a bioprinted bladder-shaped scaffold, which encouraged growth into the proper organ geometry. By employing the patient’s own bladder cells to regrow an artificial organ of the same structure and function, the medical solution was uniquely personalized.
Similarly, researchers at Heriot Watt University in Edinburgh, Scotland adapted the technology to create a 3D printer that can print the cells themselves . Rather than just printing the scaffold base and growing cells on top, their 3D bioprinter is delicate enough to print cells as well, integrating them into a more complex cell structure.
Whether the cells are seeded on top of a printed scaffold or printed by the bioprinter, utilizing patient specific cells could greatly reduce the chances of organ rejection. Organ rejection is a major problem faced when a patient’s immune system does not recognize the “foreign” transplanted organ and mounts an immune attack. Since 3D printed organs would be made of the patient’s own cells, not the cells of an organ donor, this problem would be avoided entirely.
Where Can I Get One?
Given the amazing potential of 3D printed organs, why aren’t they accessible yet? Why are 3D printed hearts not available and why is there still an organ transplant waiting list?
There are two types of challenges facing 3D printed organs. First, there are technological limitations to the complicated process of 3D bioprinting organs. Second, even for the organs we can print, there are regulatory and financial barriers to commercializing the technology to a large scale.
While research on 3D bioprinting of organs has exploded in recent years, scientists and technology still can only print relatively simple organs. Bladders and tracheas consist of one or two cell types and have a relatively simple physical structure. On the other hand, many patients are currently waiting for heart, kidney, and liver transplants. These organs have many more cell types, are much more complex structurally, and have uniquely difficult features to replicate. Printing these organs is, for now, regarded as infeasible.
To address this difficulty, researchers have found a way to “recycle” damaged organs like hearts, kidneys, and livers that are ineligible for transplant. The old cells can be removed from the organ structure (decellularized) leaving just the structural matrix behind. The patient’s own cells can then be reinserted into the decellularized structure, and the new organ can be grown. While this does not involve customized 3D printing of organs, it does allow medical researchers to “regenerate” complex human organs.
Another technical challenge is delivering oxygen to cells within the artificial organ. Cells require oxygen to live, and in the body blood vessels create a well-developed network to supply every cell with this essential element. Without the vascular network to transport oxygen, tissues and organs – including 3D printed ones – suffocate and die. Currently researchers face significant challenges with printing vasculature, which in turn hinders the creation of printed organs .
Finally, we come to the regulatory and financial challenges. Gaining FDA approval for such a radically new technology is challenging. In order to guarantee the safety of the technology, massive clinical trials and testing need to occur over a multi-year span. While researchers have been able to print amazing biological organs, it will likely be years – if not decades – before these printed organs will be deemed safe for the general public.
Tengion, a company founded by regenerative medicine pioneer Dr. Anthony Atala, holds the patent for bioengineered bladders in the US and is in the process of acquiring FDA approval. The expensive and lengthy regulatory process forced the company into bankruptcy in 2014, though it was bought back, allowing its research and efforts to obtain FDA approval to continue .
Some time from now, 3D bioprinters could be found in every major hospital around the world. Emergency rooms would have one on stand by, ready to rapidly print any organ, device, or implant on command.
The advantages of this approach are speed and personalization. For patients waiting for a lung transplant, 27% died waiting for organ transplants in the first year . 3D printing can reduce a year’s wait to just hours, potentially saving these lives.
In addition, humans are incredibly unique, and vary widely from person to person. Patients waiting for a transplant often have a hard time finding a donor who has a tissue match. Prosthetics and implants also need to fit perfectly in order to avoid later complications with function and compatibility. 3D printing could eliminate this challenge by providing customized medical solutions. In order to fit unique individual specifications, 3D printing can create organs, implants, and prosthetics precisely to the desired size and geometry.
While amazing medical advances have been made thanks to 3D printing technology, formidable barriers have yet to be overcome, stalling the large-scale reproduction of these technologies.
The complications recreating every functional characteristic of a human limb or remaking the complex environment of a human organ, paired with the monetary and regulatory challenges are grand.
Still, researchers are enthused by the amazing medical technology printed everyday. By continuing to perfect and discovery the capabilities of 3D bioprinting, researchers hope to solve physiological failure.