Research firm The Insight Partners estimates global market of 3D Bioprinting medical devices to be worth $6,583.50 million by the year 2028. The market will grow by a Compound annual Growth Rate of 17.5%.
It’s astonishing how fast the medical industry has evolved so much in almost a decade. From 2010’s Nobel for In-vitro fertilization to 2022’s brain-computer interface for the paralyzed, biotechnology has solved critical problems by creatively combining innovative technologies. What it’s now working on is a way to print human organs in three dimensions with biological material.
Imagine the impact it would have on real-world medical issues. A 3D-printed eye with full functionality would eliminate wait times and minimize the cost for eye transplants. Life expectancy across the globe would drastically increase. It’s a long shot, but the development of 3D-printed organs could lead to the development of androids as well.
3D-bioprinting: The History
The 3D-printed organ industry’s growth is a testament to biotechnologies still in theory. Its history starts in the year 1999, David J Odde and Michael J Renn released a paper on “Laser-guided direct writing for applications in biotechnology”, based on their experiment that included laser-assisted deposition of living cells. This development was complemented by K Karzyński et al in 2001 when they printed a bladder-shaped scaffold.
A year later, in 2002, the first official 3D bio-printer was created by Landers et al. This bio-printer was extrusion-based and popularly commercialized as a “3D bio-plotter”. Perhaps the most peculiar and famous 3D bioprinting tech can be attributed to Wilson and Boland’s inkjet bio-printer, developed in 2003. In addition, their team implemented cell-loaded 3D bioprinting with a commercial SLA printer.
2012 heralded the evolution of many new bio-printed inventions, like the artificial liver and articular cartilage. In 2014, biotechnologists figured out the integration of 3D printed tissues with the circulatory system. The future of 3D printed organs was proved fruitful in 2019, when Nadav Noor and Assaf Shapira printed a functional heart that could be pumped with blood. Four months later, A Lee et all were able to devise a way where hydrogels or collagen can be used to print components of the human heart.
The Process of 3D-printing Organs
The process of 3D printing organs is quite simple but challenging in practice. It’s somewhat like extrusion 3D printing a model of a toy designed on Blender. Let us walk you through the process:
The first step involves acquiring the layout, shape, and dimensions of the biological structure that needs to be printed. The virtual model can be acquired through computed tomography (CT) scans, magnetic resonance imaging (MRI), digital X ray scans, or a simple 3D photoscan using a camera.
The scan is imported into a 3D modeler, sliced into 2D layers using an appropriate software. The layers are now ready to be printed on top of each other, forming a 3D bio-structure as a result.
Selection of Matter:
Bio-inks are now available as printing material for bio-printers. These are usually hydrogels laden with a patient’s cells that are taken from a tissue. Bio-inks mimic extracellular matrix to support adhesion, functionality, and rigidity in structure. They also guarantee biocompatibility so that a patient’s body does not reject a fitted 3D organ.
Conditions necessary required for printing and prerequisite parameters are set first for printing. This may include choosing the syringe for extrusion (plastic or metal), temperature, pressure, number of extrusions, and print precision. Depending on the printed subject, the print may take a few hours or even days.
The printed structure has to be stimulated with plasma, blood, or electric surges. The process of perfusion in a bioreactor is very important as it ensures the print does not ‘die’. It’s similar to the situation when an organ is harvested from a donor and it needs to be kept fresh.
Sometimes, the printed organ needs more connections to mature, which is why it’s kept in the bioreactor for a little more time. Once the 3D printed organ is implanted, the hydrogel degrades and the cells replicate to form a bridge, connecting the organ to other vital parts.
3D Bioprinting Techniques
A wide variety of approaches can be used to 3D bioprint. The process is primarily based on three different methods: mini tissue building blocks, biomimicry, and autonomous self-assembly. These methods are implemented through the following:
Sacrificial Writing into Functional Tissue (SWIFT)
The compactness or rigidity of a human tissue is replicated by packing hydrogels and cell samples together for this method. Thereafter, channels are carved into the pack to duplicate arteries and veins. This is done through sacrificial writing, a procedure that involves burrowing channels within the pack. It’s through these channels that vital fluids and nutrients are programmed to pass. SWIFT is the closest one can get to producing functional organs.
Stereolithographic 3D Bioprinting
A spatially controlled beam of laser is exposed to a petri dish filled with bio-ink solution. The laser causes a reaction which links the organic polymers together (photopolymerization) and form a solid cross section. Layer-by-layer, the 2D pattern creates a 3D structure following which, the structure is separated from the bio-ink. Stereolithographic 3D bioprinting is a high-resolution mode of printing, much like the conventional stereolithographic printing.
Drop-based 3D Bioprinting (Inkjet)
As the name suggests, Drop-based 3D Bioprinting releases droplets of bio-ink that polymerize to create the planned 3d organic structure. Cells can directly be deposited and do not require hydrogels for this process. Drop-based 3D bioprinting is preferred by bioprinters due to its speed of production. However, this is a problem for complicated organ prints.
Extrusion 3D Bioprinting
A firm mix of bio-ink is extruded by a syringe or a portable printer head onto a platform layer-by-layer to build a 3D organic structure. An ultraviolet light source is introduced to the process for cross-linking of polymers. Extrusion bioprinting works like conventional PLA 3D printers. It’s best to use extrusion bioprinting for constructs that are strong and rigid.
Fused Deposition Modeling
Traditional Fused Deposition Modeling (FDM) printers are used to create strong scaffolds and bone-like structures to support organs. Plastic beads are heated in this mechanism and exerted on a removable plate as the printer nozzles move. It’s the most common 3D printing mechanism after extrusion 3D bioprinting and is similar to inkjet printers. Instead of a filaments or ink, plastic beads are used.
Selective Laser Sintering
Selective laser sintering (SLS) is similar to extrusion bioprinting and FDM. The only difference here is the use of powdered material as filament. SLS is best suited to print polymer, ceramic, and metal additives. It can be best used to create bone implants and organ scaffolds that require high tensile strength. A high-temperature laser guided by a computer coalesces the filament powder into a rigid planned product. Each layer is sintered on one top of the other.
An extensive scope of 3D bioprinting applications make the prospect of large-scale 3D organ printing a not-so-distant scene. Infact, recently, University of Technology Sydney (UTS) scientists and researchers claimed to create the first 3D printed microfluidic device. In league with biotechnology thinktank Regeneus, UTS researchers mapped out the microfluidic device to harvest stem cells. The cells are extracted from bioreactors and they offer an extensible way to process stem cells without incurring huge costs.
At the end of May 2022, surgeons in the United States of America successfully implanted a 3D-bioprinted ear. The recipient was a 20-year-old woman suffering from microtia, a congenital ear deformity. The 3D ear implant was bio-printed with matching parameters of the misshapen ear. What’s best about this implant is that the ear cartilage tissue will continue to regenerate until it looks like a natural ear.
American biotech company United Therapeutics created a composite 3D-printed scaffold for human lungs. This medical milestone was unveiled at the LIFE ITSELF conference in San Diego, California. The additive lung is considered to be one of it’s kind, both highly functional and complex in structure. Animal tests of the lungs suggest the lung will be easily printed using the patient’s own stem cells in the future. Additionally, the 3D-printed lung has over 44 trillion independent parts (voxels), 4,000 kilometers of capillaries, and 200 million alveoli.
3D bioprinting has evolved to the point that it can heal the planet, not just the human body. However, bioethical issues pose a roadblock to its development, which in all cases should be discussed. Directionless development of 3d bioprinting may lead to catastrophic results and loss of life.
The cost of 3D bioprinting can increase drastically if it’s not regulated. In a way. It’s harmed by its own popularity, where every biotech company may try to capitalize on the technology. Hence, a boost in demand as a result of its wake can unfavorably shoot up healthcare costs. Ultimately, the increase in demand can fall short on supply (another factor escalating costs).
Conceivably, there will come a time when ownership of genetic material and stem cells of bio-printed products are debated. The ownership debate may include patient data, research and intellectual property. If regulated properly, black marketeers of 3D-printed organs can be kept at bay. In the end, legal and medical professionals will have to work together to uphold ethical standards of 3D bioprinting.