Produce bioprinting material with microbes

Bioprinting is an additive manufacturing (AM) method for producing biological materials that can be used in medicine, as well as other industries. In the latest advancement in this relatively new field, researchers have developed a novel microbial ink (ink made from bacteria) that deploys microbes as miniature factories for bioprinting applications.

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What is bio-printing?

3D bioprinting uses additive manufacturing techniques (depositing material layer upon layer, rather than subtracting material from raw stock to manufacture new products or parts) to produce biomedical parts. Biological organisms are used to combine cells, limit or enhance growth factors, and mimic the characteristics of natural tissues.

Bioprinting is widely applied in medicine today. It is used to print whole tissues and organs that pharmaceutical companies use to test new drugs, replacing inaccurate, harmful and often unnecessary non-human animal testing. It can also imprint scaffolds that bodies will accept, allowing joints and ligaments to regenerate.

New microbial ink

Now researchers have started to modify the bacteria they use to make them more productive as tiny factories in bioprinting applications. Researchers based at Harvard University (USA) have recently developed a new microbial ink for bio-printing.

The research was led by bioengineers Anna Duraj-Thatte and Avinash Manjula-Basavanna and was published in the journal Nature Communication.

The Harvard team started with E. coli, a common bacteria. They modified the genes of E. coli so that the protein fibers emitted by the bacteria as structural support can be modified.

The gene tuning of E. coli led the bacteria to create different shapes with their structural support. The group referred to these shapes as “buttons” and “holes”. Differently modified microbes formed pimples or holes, and their growth together resulted in the manufacture of both types of protein fibers.

Further reading: Producing biofilms with additive manufacturing

When grown together, the different types of fiber structure bonded together, the knobs filling the gaps and the resulting viscous mixture becoming stiffer. The researchers filtered this mixture to remove the bacteria and included nutrients to feed them.

The remaining material containing only protein fibers is a hydrogel (a wet gel). The team found this hydrogel to be a suitable candidate for 3D printing, having a consistency similar to toothpaste squeezed out of a tube.

The team took their breakthrough one step further by adding microbes to the hydrogel mix. These new bacteria have been programmed to make anti-cancer drugs or clean up toxic chemicals in living cells.

The researchers found that the hydrogel mixture they developed is still not stiff enough to build solid objects. However, future research in this area should unlock even stiffer microbe-based inks, allowing the technology to take off.

Applications for bioprinting

There are many applications for bioprinting in medicine, and many of them are completely new. For example, a baby with a rare condition called tracheobronchomalacia received a 3D-printed tracheal splint to help him breathe. The technique is often used to reshape tissues in different parts of the body like this.

bio-printing, fabrics, microbial ink hydrogel, 3d printing

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People with end-stage bladder disease can be treated with bioprinted bladder tissue that reconstructs the organ. The same technology can be applied to bones, skin, cartilage and muscle.

Tissue engineering is a new medical field that has advanced considerably with the introduction of 3D bioprinting techniques. This is the field that develops new biomaterials as inks and substrates for bioprinting.

Sometimes biomaterials are stronger than their natural alternatives, including bone and soft tissue. These materials can be replaced by diseased or damaged tissues in the body and, in the future, may even help improve our biological processes.

Alginate is an example of a resistant biomaterial. It is an anionic polymer that has strong biocompatibility with the human body, has low toxicity, is stronger than natural fabrics, and can be produced on a large scale.

Interview: Alginate-based 3D printed inks for biomedical models

The future of bio-printing

Bioengineers are currently researching micro-channel bioprinting methods to ensure that nutrients and oxygen from nearby tissues efficiently diffuse along the tissues.

In the future, entire organs could be fabricated using bioprinting. This would eliminate any cause for animal testing, which often leads to unnecessary animal death and suffering.

Of course, producing a fully bioprinted organ would also impact the direct medical treatment of humans. This is now the goal of many bioengineers, but it has not yet been realized. Organs are much more complex in form and function than stents, as they must operate with electrical signals in the body and (changing) mechanical loads.

It seems likely that getting to this point is only a matter of time. Once whole-organ bioprinting technology exists, it must then be scaled up to ensure that its potential to improve global health outcomes is fully realized. This means ensuring that bioprinting materials, inks and substrates can be manufactured at scale, at relatively low cost and worldwide.

References and further reading

Duraj Thatte, AM et al. (2021). Programmable microbial ink for 3D printing living materials produced from genetically modified protein nanofibers. Communication Nature. Available at: https://www.nature.com/articles/s41467-021-26791-x

Rock, CD et al. (2020). Current Challenges of Three-Dimensional Bioprinting of Cardiac Tissue for Cardiac Surgery. European Journal of Cardiothoracic Surgery. Available at: https://academic.oup.com/ejcts/article/58/3/500/5835731

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