3D Bioprinting has quickly become one of the leading developments in the 3D printing industry, an industry that has seen the most growth and innovation in recent years. So far, the market has focused mainly on North America, with many companies, laboratories and universities around the world starting to move forward in this field. With 3D printing of living tissue a current reality and a great feat for the medical world, another development that is quickly gaining traction is bioprinting in relation to the production of 3D printed organs created from human cells. A scientific possibility that would mean an increase to our quality of life and an increase in more successful transplants.
But while this technology is considered to be the future of medicine, there is still many unknowns that are attached with this printing process. Below, we are going to explore this topic and some of the questions people encounter when discussing 3D bioprinting. In addition, we will also explore the different printing processes associated with this technology.
As demands for transplants by patients continues to rise every year, reaching a current total of 76,036 actively waiting donors in the United States alone (with a new person added every 10 minutes), the possibility for those who are waiting to receive a much needed organ is sometimes a dream that is never achieved. But, with the advancements and technology of today, scientists and researchers are starting to believe that there is a solution to help combat this problem. This solution? 3D bioprinting.
Using specialized 3D printers that create complex cell structures through a layering process, researchers and scientists alike have been quickly swarming this technology with the hope that it will bring future developments of printing with cells to create a functional human organ. Their overall hope? that bioprinting will alleviate the problem of patients needing transplants and will help rein in a future of medicine like we have never seen before.
The Beginning of 3D Bioprinting
3D bioprinting dates back to 1988, when Dr. Robert J. Klebe of the University of Texas presented his cytoscribing process. A method of micropositioning cells in order to construct two and three-dimensional synthetic fabrics using a common inkjet printer. Following his developments, in 2002, Professor Anthony Atala of Wake Forest University created the first organ: a small-scale kidney, created using 3D bioprinting. To help continue the fostering of innovations in bioprinting, Organovo, the first commercial laboratory, arrived in 2010 in SanDiego, California. The lab quickly began working with Invetech developers to create one of the first bioprinters on the market, the NovoGen MMX. Since then, Organovo has positioned itself as a leader in the industry, holding a strong position that they are expected to keep until 2022, as they continue to work on developments in bone tissue and making major breakthroughs, such as seen with their creation of hepatic transplantation tissue.
Because bioprinting is still in its beginning stages, printing human organs is still not an easy task to accomplish; One of the biggest challenges is the high cost of development and lack of knowledge. However, new 3D techniques are beginning to emerge to increase the chances of success and are divided into 5 different categories that we will be exploring below.
This technology is based on the classic inkjet printing process. Today, 3D FDM printers are being modified to achieve a similar printing process. This method makes it possible to deposit droplets of bio-ink (also known as biomaterials or biotins) layer-by-layer onto a hydrogel support or a culture plate. This technology can be classified into thermal and piezoelectric methods, both based on a form of biotin.
With thermal technology, it utilizes a heating system that creates air bubbles that collapse and provide the pressure needed to eject the “ink” drops. In contrast, the piezoelectric technology does not use heat to create the needed pressure. Instead, it uses an electric charge that accumulates in certain solid materials. In this case, a polycrystalline piezoelectric ceramic is present in each nozzle. A drawback with this last technology is that it can cause damage to the cell membrane if it is used too often.
Scientists have made great strides in regards to the patterns of molecules, cells and organs with inkjet printing. Molecules such as DNA have been successfully duplicated, making it easier to study cancers and potential treatments. Cells that help combat against breast cancer have also been successfully printed using inkjet bioprinting; Retaining their functions, with good prospects for creating living tissue structures or organs.
For Organovo, they rely on inkjet printing in order to create functional human tissues. Specifically, they are interested in reproducing the tissues found in the human liver. Their focus on this is in regards to the long waiting list for a liver transplant in the US. What Organovo hopes to do is to fix the damaged part of the liver, which would then provide a solution that would extend the life of the organ until the patient is eligible for a transplant. A waiting game that can sometimes take several years.
This method is based on the use of an extrusion to create 3D patterns and cellular constructions. Using biomaterials for printing, the solution is then extruded by coordinating the movement of a pressure-based piston or a microneedle over a stationary substrate. Printing consists of the printing of the model layer-by-layer, constructing itself together until the model is completed. The advantages that we find with this technology includes the ambient temperature process, direct cell incorporation and homogenous cell distribution. Some of the most popular bioprinters, such as the Bioplotter and the EnvisionTec, use this technique as it is considered to be the evolution from the inkjet bioprinting process.
Laser Assisted Bioprinting
This method uses laser as an energy source to deposit the biomaterials into a receptor. This technique consists of three parts: a laser source, a tape covered with biological materials and a receptor. The laser beams irradiate the tape, causing liquid biological materials to evaporate and reach the receptor in the form of droplets. These droplets contain a biopolymer, which retains the adhesion of the cells and helps the cell to begin growing. Compared to other technologies, laser-assisted bioprinting has unique advantages. Some specific advantages include it being a nozzle-free and contactless process that allows for high-resolution cell printing and droplet control Of biotin.
The French leader in bioprinting, Poietis, has launched a hair reproduction program in partnership with L’Oréal. The company uses the laser-assisted bioprinting technology, allowing them to deposit the cells precisely into a particular order. Today, the company is trying to recreate a hair follicle that could prove to be an effective solution to for stimulating hair grow, a potential alternative for men and women confronted with balding.
STL technology consists of solidifying a photopolymer using ultraviolet light. It has the highest manufacturing accuracy and is suitable for bioprinting as it prints with hydrogels that are sensitive to light. This technology is still currently under development because there are still many limitations, such as lack of biocompatibility and biodegradability of polymers, adverse effects, and inability to the remove supports.
Bioprinting with Acoustic Waves
Developed by Carnegie Mellon University, Pennsylvania State University and MIT, this technology uses ‘acoustic clamps’, a microfluidic device that enables cells or particles to be manipulated using superficial acoustic waves. By using this device, researchers are able to manipulate where the waves will meet along each of the three axis. At these meeting points, the waves will then form a 3D trapping node that captures individual cells. These cells are collected in order to create 2D, and later 3D patterns. An overall technique that offers high performance in terms of movement accuracy.
Over time there have been more and more developments associated with this technology, with new applications or techniques debuting fairly quickly. An example of this can be seen at the Northwest University in Illinois with their 3D printed ovary as well as in Sweden, where researchers have successfully 3D printed human cartilage tissue. But while these advancements in the name of medicine have led to exciting talk and speculation about the future, there is another side that has yet to really be touched on, and that is the ethical implications we may face in regards to this technology.
The Future of Bioprinting and the Ethical Implications it May Have
Bio-medicine techniques seek to develop “personalized medicine” where doctors will be able to tailor treatments according to the needs of each patient. One of the main concerns of the industry is the costs associated with this personalization and who will be able to access it.
Another ethical difficulty is that it is impossible today to test the efficacy and safety of these treatments. After analyzing the different techniques used, we know that it is possible to develop functional organs that can replace human organs, but it is not yet possible to assess whether the patient’s body will accept the new tissue or the artificial organ created. In addition to all of this, it is necessary to consider the legal regulations that must be created before these advances are made available to a wider audience.
We should also not fail to mention that new technologies can always be misused, and bioprinting is no exception. If technologies are capable of creating organs or tissues tailored to the specific needs of a human, considerations should be given as to the possible negative consequences of this tailored medicine. This being most notedly in reference to the potential for the creation of new super human capabilities, such as resilient bones or lungs that oxygenate differently. An attractive future for some people around the world, an even more attractive future for certain sectors, such as military.
As of 2015, the bioprinting market was valued at $100 billon, with a a growth expectancy of 35,9% between 2017 and 2022, far surpassing many of the markets that are related to 3D printing. Of course, the main players are expected to continue growing in North America, with the United States holding strong in the first position, followed by Canada. Even though this is where the market is currently flourishing the most, we shouldn’t overlook Europe, as many European countries are currently moving towards developments in bioprinting, with the current leader being the United Kingdom followed by Germany.
While the main growth that will be seen in this market will focus on the development of tissues and organs, it is safe to say that in maybe a decades time, we will be talking more about 3D printed human organs and transplants. Although there are still many great things for researchers and scientists to discover in the future, we are sure that 3D bioprinting may be one of the greatest medical developments that we will see in our lifetimes; a true revolution for the future of medicine.