Bioprinting has been a much hyped and anticipated technology development. The idea of being able to 3D print organs is a very powerful one indeed. If researchers are successful in commercializing bioprinting then life could be extended for many people. In areas such as heart disease, liver disease, cancers and implantology, bioprinting can have huge impacts. If we look critically, however, then it may take a few decades for bioprinting to come to fruition and become approved in a clinical setting. Bioprinting is one area where the general public probably has a far too optimistic view of what is possible today and where hope perhaps outweighs what is actually possible at the moment. There is a lot of research going on, however, and bioprinting will be an exciting burgeoning area for the foreseeable future. In this article we’ll look at some interesting trends and emerging research areas in order to ascertain the state of bioprinting.

Using Desktop 3D Printers for Bioprinting

One interesting emerging trend is that researchers are using repurposed desktop 3D printers to bioprint. Ultimakers and MakerBots are being used as a motion stage for syringe extruders and other printing technologies. The affordability of desktop 3D printers makes them ideally suited for the budgets of research teams. The machines are also far easier to hack and change than industrial units. Individual researchers, departments and teams are buying these machines and printing scaffolds, cartilage, bone, 3D print organs directly as well as orthopedic implants. In this paper for example a MakerBot is being used to print a broad spectrum antibacterial implant. Here a Printrbot Simple Metal had a syringe extruder added to it in order to 3D print antimicrobial cellulose.

Low-cost, affordable and replicable research machines

I believe that the greatest value that 3D printers will have in research, including in bioprinting, is that they will become experiment replication machines. Run to run differences between machines are currently too high and not enough research has been done to calibrate machines and to define all the parameters that influence 3D prints. Once that does occur however, this could accelerate 3D printing research considerably. If I can replicate your experiment at the touch of a button, then 3D printing research could be replicated and expanded upon much quicker than other research. At the moment we can see people work with many different printer settings while they are not calibrating them correctly which means that much 3D printing research is “garbage in, garbage out.” This is a shame but if ameliorated could lead to a huge boon to 3D printing researchers.

Low-Cost Bioprinters

The CELLINK INKREDIBLE fits right into your fume hood.

Existing bioprinters such as the EnvisionTEC Bioplotter or the RegenHU may cost $80,000 or more. This is why a lot of researchers are using existing desktop systems to do their research.

Increasingly we can also see another low-cost category emerging, that of low-cost bioprinters. These machines cost from $10,000-20,000 and are dedicated bioprinters. Not many of them have been sold to date but they are beginning to turn up at research organizations. If they work well they could accelerate bioprinting research and development. A Biobots BioBot one-syringe printer is only $10,000, the CELLINK Inkredible bioink system starts at $5,000. These systems have the potential to greatly enhance 3D printing research.

Tools in Research

What other medical devices could you make based on a cell phone?

In this paper we can see how various 3D printers were used to make anatomical models. Here PLA models made on an Ultimaker were printed to aid “cardiothoracic residents in flexible bronchoscopy.” This let doctors have a hands-on experience through training with 3D printed parts. Here a preoperative planning personalized liver model was 3D printed to help doctors. Here is one of several papers making low-cost microfluidic devices using desktop 3D printers. These microfluidic devices can help administer low-cost medical and scientific tests among other things. In this paper a low-cost 3D printed lens adapter coupled with an app can turn any smartphone into a retinal scanner.

The above papers can have several very deep impacts: they can expand medical testing and training making it better and more cost effective worldwide, they can let low-cost devices and parts be used in low-income countries that could not previously have such devices and they can empower individual researchers. Especially those devices that can be printed on desktop 3D printers can lower the cost of medical research and accelerate bioprinting and other research. If an anatomical model is no longer $1000 but $20 then more people can have them and use them. The democratization of research is something that can be engendered by 3D printing. There is a real trend in papers touting “low cost 3D printed” medical devices and research tools and this can have a real and significant impact on bioprinting and other areas.

3D Printing Scaffolds for Bone and Cartilage

Here PCL (polycaprolactone) was used to make scaffolds for bone tissue regeneration and here PCL scaffolds implanted in the body were tested for degradation and here tracheal scaffolds in pigs were created using the same material. Here porous ceramic scaffolds were used for bone tissue regeneration. Here 3D printed PLA and PLA Bioglass scaffolds were tested in vitro and in vivo.

Here Gelatin Alginate scaffolds are being tested for biocompatibility. In this paper PCL coated hydroxyapatite scaffolds were tested also for bone tissue engineering. Here 3D printed monite was used to regenerate bone. Vat polymerization (SLA, stereolithography) is being considered here for soft tissue scaffolds despite the issues in potential cytotoxicity with SLA resins. Here a polymer and clay hydrogel scaffold for bone regeneration is discussed. Here a handheld device called a biopen is used to 3D print scaffolds directly into the cartilage of the patient. The BioPen was developed last year and continued research in 2017. Essentially there may be a future out there where surgeons will use 3D printing pens to print inside you. Scaffolds are one of the most active areas of 3D printing research, especially in bone and cartilage regeneration. Perhaps as many as 70% of all people over 70 in wealthy countries will at one point suffer from bone and cartilage degeneration so this is one area that is very ripe for eventual commercialization.

Engineering Materials

In this paper PCL was made into a gradient material using FDM (material extrusion). Gradient materials let you vary the properties of a part throughout that part. One section could be more elastic for example. In this paper a carbon electrode was 3D printed in order to make Electric Double Layer Capacitors. These high capacity high cycle batteries could power many things if commercialized. Here we can find an overview of so called smart materials for bioprinting.

By developing completely new designer materials using nanoparticles, gradient materials, filled materials or novel microstructures scientists and engineers can find new solutions to repairing and augmenting the human body. Our bodies are very complex and new materials would greatly enhance our ability to repair them. Materials research in 3D printing is expanding and scientists are increasingly using new designer materials to solve problems in the human body. Integrated 3D printed devices such could also in and of themselves greatly expand 3D printing’s reach in research.

Personalized Medicine

Here a custom C2 spinal implant was 3D printed in titanium and implanted in a boy who had an “uneventful recovery.” Acetabular cups are already being 3D printed and implanted in thousands of patients, this paper points to customized acetabular cups as the solution. Here a customized joint replacement is 3D printed.

Additionally, people are looking into personalized drugs and personalized bone implants or scaffolds with unique drug loads for each patient. Medicine is currently a one-size-fits-all affair. Yes, you can to a certain extent change the doses of things depending on body weight and other factors but generally it is not personalized. Each of us is unique and we have very different bodies with highly differentiated organ sizes, DNA expressions, differences in our proteins and many other factors that make us very unique indeed. Personalized implants and personalized treatments in oncology are already making significant impacts in extending life and survivability. By treating one individual patient with a custom treatment made for him or her outcomes should be improved. With 3D printing it is facile to make unique structures and to give parts unique characteristics or unique surface textures. This makes 3D printing one of the technologies that could be used to implement personalized medicine at scale.  

3D Printing implants

The PLLA nanoparticle bone screws.

The PLLA nanoparticle bone screws.

Here PLLA (Poly L Lactide) bone screws were combined with metal nanoparticles. This paper looks are producing implants on demand. Personalized implants but also series of implants are already being used in tens of thousands of patients.

Recent developments include PEEK (polyethylethylketone) polymer implants being used in cranial implants and in orthopedics. Titanium implants are becoming more commonplace and new FDA approvals for specific titanium implants are being given. Typically many titanium 3D printed implants are actually lower cost (for bone especially) than those made with other technologies so the future for 3D printed implants looks bright.

3D Printing Tissue

The Wyss Institute’s 3D printed tissue.

Here 3D printed tissue is being 3D printed directly with several bioinks. Here cells are 3D printed directly inside hydrogels and this paper also discusses printing tissues directly using hydrogels. Here aortic valves are directly 3D printed. Here nerve pathways are reconstituted using 3D printing. Here stem cell patches were 3D printed to help repair hearts. Here researchers are trying to 3D print neural tissue. In this paper self assembling tissue strands are printed.

Whereas it is 3D printing organs that has captured the most headlines there are many other tissues that can be engineered and printed. Skin tissue and arteries for example would have huge impacts if they could be 3D printed at scale. Simpler tissues such as veins are also much more likely to show up in patients earlier than complete organs.

Conclusion

There is a lot of 3D printing bioprinting research going on at the moment. It is difficult to see where it is all headed and when it will make an impact on patients. I’m sure that 3D printing will promote and catalyze medical research through the low-cost creation of medical devices and tools. I’m also reasonably confident that some of the 3D printed drug loading and 3D printed tissue engineering research that is going on will make its way to humans. By creating new designer materials 3D printing can potentially expand medical solutions that we have not yet dreamt about. There is still a considerable journey to be undertaken in certification and clinical trials for the most exciting applications of the technology in organ, bone, cartilage and tissue regeneration. In implantology 3D printing is already making a significant impact on the medical industry. The hype is still too far ahead of the research and results. I do however foresee many high-impact life-extending applications for our technology in the future.

Discuss in the State of Bioprinting forum at 3DPB.com.

 

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