By Adaobi Rhema Oguejiofor
When great minds execute great ideas in order to proffer the much-needed solutions to human problems and challenges, innovation and technology comes alive, the world witnesses its power and recognizes its worth. One of such revolutionary solutions that offers life changing opportunities is bioprinting.
Bioprinting, which is also known as 3D bioprinting, is an additive manufacturing process that involves the combination of 3D printing with biomaterials in order to replicate parts that imitate natural tissues, bones, and blood vessels in the body. It has led to remarkable advances in the healthcare sector, especially in the area of regenerative medicine, as it facilitates on-demand “printing” of cells, tissues and organs. This technological innovation has also led to the creation of new scientific fields, such as “tissue engineering”.
For patients who are in need of organ transplant, bioprinting is a ray of hope. According to the United Network for Organ Sharing (UNOS), as of January 2023, there were more than 107,000 people in the United States waiting for an organ transplant on the national transplant waiting list.
There is a longer wait-list for organs all over the world, as the need for donations is much higher than the number of available organs and within every 10 minutes, another person is added to the organ wait list. The World Health Organization (WHO) estimates that the black market that has been created by this soaring demand for organ transplant, results in 10,000 illegal transplants each year.
The developments in 3D bioprinting have been largely motivated by the limited availability of organs, which are needed for the rehabilitation of lost or failed organs, as well as tissues, and this limited availability is on a global scale.
In the medical field, bioprinting has been employed to help study or recreate almost every tissue, cartilage, and organ in the body. The technology uses a digital file as a blueprint to print an object layer by layer. But unlike 3D printing, bioprinters print with cells and biomaterials, thereby creating organ-like structures that let living cells multiply.
Although the bioprinting technology is relatively still developing, it has a huge potential to benefit industries like regenerative and personalized medicine, drug discovery and cosmetics. It is providing new options for treatment and scientific study.
Bioprinting, which involves the production of complex living and non-living biological products from raw materials, such as living cells, molecules, extracellular matrices, and biomaterials, works when the required cells like kidney cells, skin cells, among others, are taken from a patient and then cultivated until there are enough to create the ‘bio-ink’, which is loaded into the printer.
Bioinks are made of natural or synthetic biomaterials that can be mixed with living cells. Following detailed computer designs and models, often based on scans taken directly from a patient, precision printer heads deposit cells exactly where they are needed and over the course of several hours, an organic object is built up using a large number of very thin layers.
Generally, more than just cells is required for the process, so most bioprinters also deliver some sort of organic or synthetic ‘glue’, which is a dissolvable gel, collagen scaffold or other type of support that the cells can attach to and grow on. This helps the cells to mould and stabilize into the correct form. Some cells can even assume the correct positioning by themselves with no scaffolding.
One might wonder how these cells know where to go. How they locate their intended destination is that they use their inherent properties to seek out cells that are identical to them to join with. They naturally know where they are needed, similar to the way cells in an embryo develop in the womb, or tissues in an adult move to repair damage.
When this occurs, researchers are then able to control the shape in which they do that, with the printer building the final structure.
Thomas Boland, a bioengineer at the University of Texas, El Paso, pioneered bioprinting in 2000 when he used a Hewlett-Packard inkjet printer to print a bioink made of living bovine cells suspended in cell-culture medium. But since those early days, 3D bioprinting research has tackled increasingly difficult problems with different approaches. One of these approaches involves concocting a bioink that not only delivers cells but also provides the extracellular, matrix-like scaffold that tissues need for structure.
Paul Gatenholm, a professor of biopolymer technology at Chalmers University of Technology and Director of the University’s 3D Bioprinting Center, said that because skin and liver cells have different physical properties and nutritional needs, inks have to be developed specifically for the tissue to be printed.
According to Gatenholm, an ink needs the right balance of flow properties and consistency, typically similar to toothpaste, so that it can be extruded from nozzles but still maintaining its shape. It also needs biomolecules and chemicals that allow cells to migrate, attach, communicate with each other, and proliferate after printing. He added that it has to be reproducible and storable, which makes it more and more complicated to design and prepare bioinks.
Sharon Presnell, the Chief Scientific Officer of Organovo, an organ printing company, stated that it should be possible to print tissue patches to repair failing human organs within the decade. Although human tests are far away, the idea is to use cells harvested from the patient so that the tissues are accepted by the immune system.
Under such circumstances, whether or not these body parts look like the real thing, they would do the same job. And 3D printing would allow them to be printed on-demand, in hours, and for a low cost, which will help save thousands of lives across the globe.
Bioprinting is carried out in three stages and they are the pre-bioprinting, bioprinting and post-bioprinting. The pre-bioprinting stage involves the production of the digital model that will later be printed and the selection of the materials that will be used. Images are usually created with computerized tomography or magnetic resonance imaging and once finalized, certain cells are isolated, multiplied and combined with the selected bio-ink.
For the bioprinting stage, it is the final realization step that takes the foundational work and builds the required tissue sample. It is ready for incubation and the planned uses for drug evaluation, toxicity testing, or patient implant. At this point, the cell-laded bio-ink is placed into a cartridge and the necessary printheads for creating the target structure are selected for the process.
Then at the last stage, which is the post-bioprinting stage, it is necessary to ensure the stability of the printed structure. This stage involves providing the structure with mechanical and chemical stimulation to control cell growth. After bioprinting, there are various critical processing steps that ensure the function and viability of the built tissue. Finally, the bioprinted tissue will be tested to ensure it is functioning as expected. A wide range of possible tests are available and suited to particular tissue types.
Bioprinting has three distinct types and each type comes with its difficulties and benefits. The three types include the Inkjet-based bioprinting, Pressure-Assisted bioprinting, and the Laser-Assisted bioprinting.
For the Inkjet-based bioprinting, it makes use of specifically modified inkjet printing to place living cells and biomaterials onto a stereolithographic 3D construct in order to build biological structures, tissues and organs. The major benefits, as well as outstanding characteristics of Inkjet-based bioprinting, is that it is high resolution, high speed, and suited to applying multiple cell types or biomaterials in one print. Although it is far from mainstream as of present, this technology is a key experimental method in tissue engineering for regenerative and implant medicine and also in drug testing.
The pressure-assisted bioprinting on the other hand, uses a pneumatic or hydraulic-driven delivery of fine droplets of bio-ink onto a build platform. This constructs the tissues as designed in a layer-by-layer process and is simpler in many regards than the other alternatives.
It also allows mixed cell placement, for closer replication of real tissues and its resolution is lower because it is extruded-droplet-based. In many cases, this is a small disadvantage to an otherwise powerful tissue construction method.
The laser-assisted bioprinting uses a laser to transfer and precisely deposit living cells or biomaterials onto a build platform. It creates the desired 3D biological structures, such as tissues and organs. Laser-based bioprinting offers various benefits over other 3D printing techniques, including high-precision control over cell placement, the ability to print with high resolution, and the ability to use a range of biomaterials, including those with more complex compositions.
However, excess laser power can result in cell damage and the technique is poorly equipped to deliver high cell densities.
Bioprinting is a powerful set of techniques that is enabling increasingly powerful capabilities across most areas of patient healthcare, drug development, environment, and toxicity testing. It is beneficial as it allows the precision building of complex tissue structures and can be used to create 3D models of organs for drug testing, which allows for faster and less ethics-restricted testing of drug formulations.
It also reduces the need for animal testing and can create custom implants, tailored to fit a specific patient’s needs. Bioprinting can build living tissues and organs for transplant, even though this capacity is limited to simple structures as yet. Since bioprinted organs and tissues will be built from the patient’s cells, rejection is shown to be minimal.
Although quite beneficial, bioprinting has severe limitations that are the subject of extensive research. Some of such limitations are that it cannot currently print complex tissues and organs with various cell types, blood vessels, and nerves.
Bioprinting materials are expensive and difficult to produce. The mechanics of the printing processes often damage or destroy cells and this limits the viability of the printed tissues. It is also still an expensive and intensively lab-based technology that uses expensive equipment and requires extraordinary skills.
There are also currently no standards or widely accepted guidelines for the practice and assessment of results between methods and research groups is quite challenging. However, bioprinting is set to become the primary regenerative surgery tool for a wide range of degenerative diseases and physiological conditions.
The process of printing a new, functional heart to replace a patient’s damaged one is still a faraway possibility, but the early building blocks and steps are being set in place. Presently, bioprinting is reducing the cost of drug evaluation and certification cycles. It also lessens the barriers to market entry for novel pharmaceuticals, thereby driving innovation in the medical sector and restoring hope.