3D Bioprinting Technology Research

Technology Finest Invention: Three Dimensional Bioprinting

In today’s medical world, various complications have developed which certainly need addressing. One of the areas giving medical practitioners sleepless nights is that of organ transplant. Sometimes, organs in the human body fail and require a transplant from another human. The organs being used for transplants are mainly those given by donors. Thus, a common scenario in most hospitals is people who need organ transplant waiting in queue for years until the next donor organ is available. Such a waiting can be very painful to the patients and, in extreme cases, leads to their death in the queue. Medical practitioners have to look for the alternative to cut the donor from the organ transplant process. The research, therefore, suggests 3D-bioprinting as one of the best ways to do this. The aim of the paper is also to answer the question whether bioprinting technique would be able to develop effectively in the nearest future. Success in this area would mean a decrease in the crisis of the organ transplant, which is currently one of the most critical areas of medicine.

Organ printing is the production of artificial human organs such as a heart, a kidney, or even a bladder for organ replacement using 3D printing techniques. Organ printing can be also defined as a computer-aided 3D technology cell aggregated into a 3D gel with the maturation of the developed structure in vascularized tissue or organ. According to Hwang, Kiang, and Paul (305), organ printing involves constructing physical objects from digital models. Organ printing has been developing since 1934. Despite such long existence, minimal success has been achieved in this sphere as many people considered organ printing as a new field. However, in 2003, Thomas Boland, the scientist of Clemson’s University, made a breakthrough in organ printing: he patented the inkjet printing with the use of living cells. He successfully used a spotting system that was usually modified to deposit cells in 3D matrices placed on a substrate. Therefore, a foundation of bioprinting has been formed. One of the organizations keen in delivering in the field of organ transplant is the Wake Forest Institution. This institution performs researches in regenerative medicine and applies their results to clinical therapies. Anthony Atala, the Managing Director of Wake Forest and one of the leading scientists in regenerative medicine, states that this field comes in to combat the organ crisis where the number of people who need organ transplant has increased while the number of organs present has diminished.

Using 3D bio printing, various organs, and other body parts have been artificially constructed and used on real people. Artificial bladders and urine tubes have been successfully implemented and tested on real patients. Another example of organs made using 3D printing is the trachea. Doctors developed a trachea for a patient whose trachea had failed (Chang et al. E95). According to the article in Global News by one of the staff, prosthetics are also being made to help amputees. Also, in the book The Culture of Organs (1938), Alexis Carrel clearly describes some of the techniques used for suturing blood vessels and even some of the grafts of blood vessels. Despite the above-mentioned achievements, the production of organs with more complicated structure, namely, heart, liver, and kidney, is still being developed and if successful could be one of the greatest technological heights reached in medicine. Most importantly, using this technology, scientists can bypass the need for donors (Nelson 2). This is made possible by developing artificial organs, and in the process not requiring donors to give organs to the patients. They would not have to queue for organ donations. Moreover, 3D printing has two more advantages: it is customizable and affordable by most research institutions.

During the printing process, the organ’s structure is constructed layer by layer, forming a cell scaffold. After this, a process called cell seeding starts: cells of interest are interconnected directly using the scaffold structure as the underlying foundation. Research has also been conducted to integrate cells into the material used for printing itself in replacement of seeding. During the printing process, modified inkjet 3D printers are used to produce the 3D biological tissue. Instead of filling the printer cartridges with ink, a suspension of living cells is used. In addition to such a suspension, one needs a special smart gel to provide the proper structure of the organ. Interestingly, a normal print nozzle is used in 3D-bioprinting process. In the end of the process, the cells fuse together to form the tissue, which has to be cooled and washed from the smart gel. Finally, only the live cells are left.

In regenerative medicine, one predominantly uses scaffolds, cells, and biomaterial (the actual substance that creates the organ and can be implanted to the organ to aid in its regeneration) for the purpose of printing. The cells can either belong to the patient or be of different stem cell populations, or both. Also, together with the cells, biomaterial is used as a bridge to aid the process. Biomaterials are the substances needed to repair or replace the structure of a specific organ: new cells grow on the biomaterial and, thus, regenerate the whole organ. Stem cells which are cells that have the capability of growing other cells of the same kind, from which other kinds of cells grow by differentiation, are especially useful in organ repairing as they can be used as any specific type of cells, for instance, heart cells.

Importantly, stem cells can also be printed and used to get various kinds of human tissue. In cases of organ replacement with large structures, the patient’s cells are used together with cell population, scaffolds, and biomaterials. Cells from the organ are taken and grown outside the body. Then, the structure of the artificial organ is created using 3D printers. During this process, the structure is subjected to human-like body conditions, i.e., 95% oxygen, and 370°C temperature.

This has been the foundation to the printing of other tissues and has led to the direct printing of different organs’ cells. Nowadays, researchers are also working on printing skin grafts. This breakthrough could offer advances to skin cancer patients, namely, treatments of burns and other complications related to epidermal cells. Moreover, 3D printing is used to print cancerous cells to study their growth and development effectively. Other research areas of 3D printing in medicine include bone and cartilage cells, and various tools used during surgery. An example of this is a study To Treat Pediatric Tracheomalacia by Zopf et al. (66-71). Doctors constructed cartilage cells and fitted them ina patient who needed them.

For the construction of these structures, scientists use various technologies. The first technology is to use discard organs. Consider an example, a liver, which is not being used, can be taken. The liver structures are then put in a machine that aids in the removal of the cells, leaving behind the liver’s complete skeleton structure with no cells. Using the structure as a foundation, the cells are grown. This approach leaves the blood vessel structure intact. Firstly, the blood vessel tree is fitted with the patient’s actual blood vessel cells for its growth. Next, the parenchyma cells are fitted with actual liver cells.

One of the biggest challenges faced by scientists in regenerative medicine is the design of materials that would do well once inside the human body. Owing to different medical advances, this has been finally achieved. Another challenge was that scientists could not get enough cells from a human body to grow an organ outside the body. However, this problem has been successfully solved in the last two decades. Despite such achievements, some of the complicated cells such as pancreatic, liver, and nerve cells still cannot be grown outside the body. This is because the structures of these cells are complicated to grow outside the body. The final challenge that scientists were facing over the years was vascularity – supplying blood to the regenerated organs and tissues to make sure they survive.

3D technology is another technique used in regenerative medicine. The main advantage of using 3D printers is that the actual printing of the organ’s structure takes less time, which is approximately forty minutes. In 3D printing, two approaches are applied: inkjet or drop-based printing, and extrusion bioprinting. Drop-based bioprinting develops cellular constructs using specific droplets of the material being used. After the droplets contact with the organ’s structure, polymerization occurs, leading to the formation of a bigger structure. Calcium ions present trigger the polymerization. The droplets then diffuse in the organ’s structure forming a solid gel. In extrusion bioprinting, a particular printing material is deposited from an extruder. Advantages of this strategy are that more control during the deposition can be reached, and greater cell densities can be obtained. Scrutinizing the disadvantages of extrusion bioprinting, one should mention that the approach has lower printing speed comparing to the drop-based printing. This approach is made possible by using UV light, which allows to photopolymerize the printed material and, thus, construct more stable and better-integrated organ. A 3D elevator heads down a level of a layer at a time every time the printing nozzle goes through. After the structure is completed, it can be implanted in the patient’s body.

More effective technique, which is currently researched, is the use of more complex printers whereby the actual printing of the organ can occur on the patient. In this technology, a flatbed scanner examines the organ to show its dysfunctional parts. Then, the information about the layers of cells is formed. Finally, the printer produces the required parts of the organ on the patient using a specific gel, and once the cells contact the organ, they quickly stick to it. The main challenge in this technology is the production of solid organs, for example, a kidney. A kidney is a large vascular organ with a complicated vascular tree of many cells. In this research, the underlying principle is to scan the whole organ with basic CT-scan or x-ray. Afterward, a computerized morphometric analysis of the image is conducted, and 3D reconstruction of the patient’s kidney is performed. All the volumetric characteristics of the kidney are captured in the 3600 rotational imaging. These characteristics are then fed to the printer layer by layer leading to an actual design of the patient’s organ. The printing time for this process is about seven hours.

Various materials are used during the printing process. Typically, the materials that contain fiber or alginate polymers are combined with molecules that support cellular adhesion. Consequently, the physical gluing of the cells to the structure becomes possible. The alginate polymers are constructed to allow cellular integration and aid in the maintenance of the organ’s structural stability. Furthermore, all printing materials have to be biodegradable and biocompatible. Biodegradability refers to the material’s ability to get broken down after being successfully transplanted and in its place. Biocompatibility, in turn, ensures that the used material structurally and physically allows the growth of natural cellular structures. Therefore, customizability and adaptability are the core characteristics of any materials used for bioprinting. An emerging trend in the sphere of bio printable materials is the development of hydrogel alginates, which are highly customizable and can fit various biological and mechanical properties consisted of natural tissue. Such characteristics make hydrogel alginates the most suitable materials for the construction of various organs, and tissue structures.

Despite the various successes reached in the research of 3D organ bioprinting, some challenges are still being faced. Firstly, the clinical implementation of the organs with complex structures such as liver and kidney still needs to be researched thoroughly. Secondly, the testing of the cell integration in the organ’s structure is conducted in external environments that are void of natural body processes and signaling. The absence of these characteristics hinders the development of organs with the proper cell adaptations. If the various body signals and processes were present, the organs developed would be suitable for the various body conditions, with the correct functioning and structure. Another challenge being faced is the development of vascularized artificial structures that are the basic requirement for any cell to live. Even nowadays, this has not been fully implemented in bioprinting. Various religious and cultural conservatives see 3D organ printing as nature manipulation and, therefore, choose to oppose these scientific advance. Moreover, the development of bioprinting might also bring social differentiation since these organs can only be available to people who can afford them. 3D bioprinting might also result in the theft of intellectual property. Then, a challenge comes in the assumption that bioprinting achieves development of complex organs and their cellular structure. Finally, one has to answer the question who will be the managers of the production of the organs, and how will the quality of the produced organs be maintained. Therefore, institutions and regulations to manage 3D organ production have to be created to manage these activities.

Luke Massella was a patient suffering from spina bifida. At that point of his life, doctors told his family that Luke’s only options were either traditional kidney transplants or a lifetime dialysis. These options did not provide a normal life such as playing or even spending quality time with friends. Luke’s family decided to try an experimental surgery, which became the first one of 16 surgeries that doctors later performed on Luke. Cells from his bladder were used for the regeneration of a new bladder using 3D bioprinting. Since Luke’s cells were used during the regeneration, the organ became compatible with his body. To Luke, this provided the road to recovery: after the surgery, he could live like a normal kid and even became the captain of his high school’s wrestling team. From this case study, one can deduce that 3D bioprinting has been successful in clinical therapies.

In conclusion, bioprinting technique can be used in the development of implantation process of various organs and tissues, thus, removing the need for organ donors. This move could reduce the crisis in the health sector ensuring that patients would not need to be queueing for an organ transplant. For this to be actualized, the various issues and challenges facing 3D organ bioprinting need to be solved. Research needs to be continued in various sectors of 3D bioprinting such as the clinical therapy of complex organs and the construction of vascularized artificial structures. Various stakeholders such as religious communities and other conservative groups need to be more involved in this discussion to make sure that there is no opposition to the development of organs. Additionally, various laws, regulations and control institutions need to be put in place to handle the control and quality of the production of body tissues and organs. The laws to prevent the theft of intellectual property should also be created. Finally, production methods need to be subsidized to enable organs to be accessible to people with different financial capabilities. If all the above measures are put in place, then the medicine will be headed in a good direction.