In his recent report on 3D bioprinting, Brian Drab, an equity research analyst covering advanced manufacturing and industrial technology, writes that the ability to generate human tissue—and eventually organs—has the potential to fundamentally change medicine and human health. For example, tissue structures produced with 3D bioprinting can accelerate drug development by allowing pharmaceutical companies to collect more meaningful data relative to tests conducted on animals or through traditional in vitro methods.

In addition, patient care can become more personalized, with 3D bioprinting enabling doctors to use the patient’s own cells to test drug reactions and/or grow new organs. On the consumer side, 3D bioprinting has the potential to replace animal testing and accelerate time to market for cosmetics. There are many additional applications for 3D bioprinting, and we believe the industry should continue to grow in the near and longer term.

And while several decades or further off, 3D bioprinting has the potential to provide individuals with electronics built into tissue, organs that can exceed current capabilities, and bodily features, like heat- or ultraviolet-resistant skin.

Drab dives deep into 3D bioprinting, examining the field’s opportunities, challenges, and progress, before offering a glimpse into some of the public and private companies working to develop and commercialize various technologies.

What Is 3D Bioprinting?

Three-dimensional bioprinting is a form of additive manufacturing (AM) that uses biomaterials, including cells, instead of plastics and metals to create functional 3D tissues. Biomaterials, also called bioinks, are designed to simulate the composition of human tissues. Bioprinting can serve various medical applications, such as the production of 3D cell cultures, drug discovery and development, and regenerative medicine (i.e., repairing lost or damaged organ functions—and potentially the manufacture of complete organs). Bioprinted structures enable the study of bodily functions outside the body in complex, 3D models and are more accurate representations of biological systems than 2D in vitro models. As a result, bioprinted structures offer the opportunity to generate more useful data in various applications.

The 3D bioprinting industry is in the early stages of development, with companies taking a variety of approaches to expand adoption and develop the necessary technology to eventually print full human organs. To be clear, we believe the industry is likely still more than a decade away from 3D printing functional, full-sized organs (although some companies have set more ambitious targets). There are near- and medium-term opportunities for bioprinting, however, such as drug development, cosmetics, and the repair of damaged or diseased tissue.

How Does 3D Bioprinting Work?

Like traditional 3D printing processes, 3D bioprinting starts with a model of a structure, which for 3D bioprinting is typically based on a computer tomography (CT) or magnetic resonance imaging (MRI) scan. The 3D model is then sliced into thin layers. Once the model is sliced, the structure is printed layer by layer with bioink(s) that either have live cells mixed into the ink or are added once the print is complete. In many ways, 3D bioprinting is different from traditional 3D printing. Although some traditional 3D printing technologies are capable of high-precision prints with layers only microns thick, this is the extreme rather than the norm for traditional technologies. In bioprinting, extreme precision is a requirement. In addition, when choosing biomaterials to be printed, a compromise is generally needed between the printability and biocompatibility—the ability for a construct to perform its desired function and support the necessary cellular activity. Many bioinks are unable to support their own weight to achieve structural stability, or their viscosity is either too high or too low to enable accurate printing. Both natural and synthetic polymers can be used in bioinks, although natural materials are preferred given their superior biological properties, but these natural materials are often lacking mechanically. In some cases, crosslinking is used to enhance the mechanical properties of the bioinks, but this process diminishes biocompatibility in some cases.

3D Bioprinting Technologies

The printing technologies used for 3D bioprinting are typically separated into four categories: extrusion, droplet, stereolithography (SLA), and laser-assisted. All four technologies have advantages and drawbacks, although extrusion, droplet, and SLA-based technologies are the most commonly used given that laser-assisted 3D bioprinting systems are generally more expensive and thus less scalable.

Extrusion bioprinting. In extrusion-based 3D bioprinting, the bioink is extruded continuously out of a nozzle via a mechanical piston or pneumatic pressure and produces filaments instead of droplets. The technology can be used with a wide variety of materials and has precise deposition capabilities, which helps control cell distribution. In mechanical extrusion, the process is driven by a stepper motor that turns a threaded screw. The screw turns the rotating motion into linear motion to push down on a piston, which forces the bioink out of a syringe. A needle serves as the nozzle and defines the diameter of the extruded material. As a result, extrusion-based bioprinters are unable to consistently control the droplet size and require more viscous bioinks. In pneumatic extrusion, compressed air is fed by a pump through the syringe that deposits the material. The pneumatic print head is more compact than the mechanical; however, it requires an external pump, which adds to system cost. In addition, pneumatic extrusion is contact-free, which can improve sterility and lessen cell damage. In general, extrusion-based technologies have the advantages of lower equipment costs, the ability to use various materials, and high cell viability post-printing, which is beneficial for complex structures. Extrusion-based bioprinters, however, also generally print at slower speeds and lower resolution than other technologies. In addition, the extrusion process has the potential to cause cellular damage during the printing process.

Droplet bioprinting. Droplet-based 3D bioprinting systems typically use either piezoelectric drop-on-demand (PDOD) or high-speed micro-solenoid valve technology. In PDOP, a piezoelectric valve, also known as a push-pull mechanism, is used as a droplet generator by squeezing the print head to form a droplet outside the nozzle that is held by surface tension. The valve is then released, which pulls the bioink back as the droplet is dispensed. Similar to extrusion-based 3D bioprinters, high-speed micro-solenoid valve 3D bioprinters are driven by a step motor. The motor, however, pushes bioink through a syringe pump that is connected to the micro-solenoid valve for a more controlled release of material. The droplets of material are formed in the nozzle through a combination of the syringe pump and the micro-solenoid valve attached to the print head. Largely due to droplet-based systems using lower-viscosity bioinks, the main advantage they have over extrusion-based systems is the ability to print high-resolution constructs while also maintaining high cell viability of about 80%-95%. Less-viscous bioinks impose less shear stress on the cells and provide higher printing resolution (droplet size as small as 50 microns) as well as improved accuracy and printing speed compared with extrusion. Droplet-based systems, however, can only use less-viscous materials, like alginate or collagen, which can make it difficult to print supports for taller 3D constructs. The nozzles can also clog when working with high-cell-density materials.

Stereolithography bioprinting. Stereolithography 3D bioprinting is a laser-based printing technology that uses a digital micromirror device (DMD) to reflect the laser onto a vat of photocurable bioink (known as photo-crosslinking). The DMD generates a dynamic mask that contains a 2D pattern of each layer. Once the laser is powered, the 2D pattern is reflected onto the vat of bioink (with or without cells) and cured by the laser. When the layer is cured, the vat will then be automatically moved up or down for the next layer, and the process repeats until the build is completed. Compared with the previously discussed printing processes, SLA-based technologies enable faster print speeds with higher resolution (20 to 50 microns) and still provide 75%-90% cell viability. SLA-based bioprinting systems can also work with any photocurable bioink, which allows the systems to produce high-cell-density constructs without potentially damaging the cells from shear stresses, like in extrusion. The bioinks (and cells if applicable), however, must be loaded into the vat prior to printing. In addition, photo-crosslinking—a process that uses ultraviolet and visible lights to allow rapid and durable curing by forming additional molecular bonds (i.e., improves natural biomaterials mechanical properties)—can negatively impact biofunctionality and biocompatibility.

Laser-assisted bioprinting. The other main laser-based 3D bioprinting technology is laser-induced forward transfer (LIFT; also known as laser-based drop-on-demand). This process uses laser energy to transfer cell droplets from a thin film of bioink to a receiving substrate. In the LIFT bioprinting process, a laser is pulsed and reflected by a digital scanning mirror onto a donor slide that contains a transparent support (e.g., glass), an energy absorbing layer (e.g., gold or titanium), bioink, and any other biomaterials needed for the application, like hydrogels. As the laser pulses and is directed by the digital scanning mirror, the laser causes local evaporation of the energy absorbing layer, which creates a bubble in the bioink. The bubble then expands and collapses, causing a droplet of bioink to fall onto the build platform. LIFT technology enables the control of multiple parameters, including droplet volume and size, printing patterns, and cell concentration, all with high precision (10 microns), repeatability, and print speeds up to 10,000 drops a second. LIFT bioprinting systems are also nozzle-free, mitigating challenges associated with shear stresses or photo-crosslinking, helping lead to cell viability over 95%; however, LIFT bioprinters use lower-viscosity bioinks, which do not typically carry strong mechanical properties.

To request a copy of the full length “3D Bioprinting: Companies Revolutionizing Healthcare and 3D Printing” report or for more information on the companies from Brian Drab’s coverage list, please contact us or your William Blair representative.