3D printing and other technological innovations have revolutionized design and manufacturing. Now bioprinters and other technologies are poised to significantly impact and “digitize” medicine.

Figure 1. 3D bioprinting process for regenerative medicine applications. Source: Zhang et al, Composites B, Elsevier, 2017

What will a future with technology-intensive healthcare look like? One could imagine instant, in-home printing of fingers or toes after accidents, sewn onto hands and feet with robotic arms. Emergency rooms could become things of the past, and bioprinting could even help enable colonization of other planets.

Bioprinting

Although it may sound like science fiction, bioprinting is poised to revolutionize medicine and healthcare. Research reports propose that bioprinting will be an important tool for future planetary colonization efforts. Hospitals with sophisticated medical equipment for diagnosing and treating disease will be millions of miles away and unreachable. Using 3D printed prosthetics and bioprinted replacement body parts might be a more viable and efficient option.

Figure 2. OrganAut, the first bioprinter used in space to print living tissue and microorganisms. Source: 3D Printing SolutionsThe BioServe Space Technologies Center at the University of Colorado Boulder is working with NASA to enhance life science research on the International Space Station (ISS) with bioprinting (NASA: Bioprinting in Space May Lead to Breakthroughs in Cancer Research). The researchers believe bioprinters can improve the cell culturing process.

Cells normally propagate and form a 2D culture in a petri dish on Earth. In space, cells exhibit spatially unrestricted growth and assemble into complex 3D aggregates. Bioprinters in space should reduce cell loss, form shaped cultures and enhance cell retrieval for analysis. After a crash destroyed the first attempt to launch a bioprinter, Russia’s Organ.Aut 3D bioprinter from 3D Bioprinting Solutions successfully reached the ISS on December 3. ISS astronauts have already bioprinted a mouse’s thyroid in the station’s zero-gravity environment, which is the first printing of living tissues and microorganisms in space. The ZeroG bioprinter designed and built by Allevi in partnership with Made in Space is currently going through the NASA safety and durability approval process.

Figure 3. Allevi 2 bioprinter. Source: AlleviHere on Earth, conventional 3D printing and additive manufacturing are already having an enormous impact on medicine. Renishaw, for example, and other 3D printer suppliers produce additive manufacturing systems specifically tailored for dental and medical applications. Their Laser Implants product line consist of titanium 3D printed craniomaxillofacial (CMF) patient-specific implants (PSIs) and surgical guides that can be provided with optional polycarbonate anatomical models. Renishaw's 3D metal printers can additively manufacture dental crowns, bridges and implants.

Implants can be designed directly from computed tomography (CT) scans and delivered in as little as five days. Custom-fit devices like hearing aids and Invisalign orthodontic braces are commonly 3D-printed.

Bioprinting Applications

A plethora of research exists and is continuing to grow in the field of bioprinting and tissue engineering. Tissue engineering (TE) is a multidisciplinary science, which includes principles from biomaterial engineering, biology and medicine. Its goal is to develop synthetic and biological substitutes to restore damaged tissues and organs. Bioprinting is a fundamentally important tool for tissue engineering. Bioprinters create organs, tissues and biological devices by printing bioinks layer by layer similar to 3D printers. Advanced bioprinters are leveraging microfabrication and microfluidic techniques.

Many therapeutic applications are envisioned for bioprinting, including reconstructive surgery and synthetic organ alternatives for donor transplants. Bioprinters can also be used to create biological analogs or “organ models” for use in screening new medicines. Structurally and functionally accurate bioprinted human tissue models will allow the equivalent of in-vivo testing without harmful and expensive animal testing or patient trials. The harmful or beneficial biological activity of drugs is currently tested in the laboratories using a two-dimensional layer of liver cells in a petri dish followed by animal testing and human patient trials. Researchers believe bioprinted organs or models will be superior in predicting the toxicity and efficacy data needed for drug discovery and development, better than animal models or current cell models.

Researchers have already bioprinted functional mini-organs, or organoids, for use in studying diseases and drugs. Organovo researchers have bioprinted livers that functioned and lived for five days. Organovo offers contract testing services utilizing ExVive 3D bioprinted human liver tissues. The 3D bioprinted construction of parenchymal hepatocytes will provide a response closer to a liver in a body. In 2015, researchers at 3D Bioprinting Solutions successfully bioprinted and transplanted a thyroid gland into a mouse, which is another historic first. Eventually, bioprinting will create synthetic human models, “organ on chip” or even “body on chip” analogs, for patient-specific diagnostic, drug, therapy and environmental studies (Meet Chip: Liver).

Bioinks

Bioinks consist of mixtures of living cells and scaffold material. The scaffold material consists of support materials that provide shape and protect the living cells. Certain types of cells self-assemble or organize into the correct shape on their own. The scaffold materials include dissolvable hydrogels, foams and polymer networks.

Figure 4. Bioink cartridges for bioprinting skin, bone, collagen, scaffolds and other tissues. Source: Cellink

Unlike the high temperatures in plastic filament deposition (FDM) or metal selective laser melting (SLM) 3D printing, bioprinting with living cells needs to occur at temperatures of 37° C or lower to maintain cell viability. Porous supports or scaffold without cells can be printed at higher temperatures and then infused afterward with living cells, nutrients and growth-enhancing factors. Researchers are developing the technology to bioprint bone, skin, blood vessels, muscles and complex organs.

Cellink, Aspect Biosystems, Allevi and many biofabrication companies are developing lines of bioinks for specific tissues. Tissue engineering with bioprinters may allow upgrades such as hyperelastic bone, bone reinforced with carbon fibers or tissue made conductive with graphene. Fundamental modifications to human biology using synthetic biology, cell engineering or programming and gene manipulation will provide future humans with even more enhancements.