Bioprinting: How To 3D Print Human Tissue

Organ transplantation is the pinnacle of medical achievement of our time. But, it is a high-risk procedure for the patients, and oftentimes it requires total restraint from poor lifestyle choices. This means that although it’s one of humanity’s greatest feats, it has challenges of its own, too.

The risks involved in organ transplantation are high compared to other life-saving procedures. So to guarantee success and better survival rate of patients post-transplant, the procedure requires complex set of protocols where surgeons and patients should follow.

In addition, it needs developments in surgical technique. We need to adopt a better strategy to suppress the body’s immune response so we don’t risk transplant rejection. Also, we need to come up with better anesthetic and intensive care.

Well, there is an emerging field that could potentially spur revolution in medical sciences. The field we are talking about is 3D bioprinting.

More than hundreds of thousands of people are waiting for a transplant. Unfortunately, there are not enough donor organs available for everyone in need. But what if we could make organs from practically nothing? That’s the idea behind bioprinting.

What is 3D Bioprinting? How does it work?

3D Bioprinting is a division of regenerative medicine currently under development. It aims to offer spatial placement of cells, proteins, DNA, and other active biological ingredients with high degree of precision. This emerging field promises advanced tissue engineering toward vascularized tissue and organ fabrication for transplant.

We are still a long way from printing complex organs just yet, but we have achieved significant success in carrying out the work on simple tissues like blood vessels and tubes responsible for nutrient and waste exchange. 

In 3d printing, we put successive layers of material (either metal, plastic or ceramic) to construct a three-dimensional object one slice at a time. However in bioprinting, we use bioink – a printable material that contains millions of living cells.

Types of bioink materials

The most commonly used types of bioink materials in bioprinting of organs and tissues are scaffold-based bioink and scaffold-free bioink.

In scaffold-based bioink, cells are filled in hydrogels or similar water-rich materials and bioprinted into 3D tissue and organ constructs. Millions of living cells loaded in hydrogels promote cell growth and formation of tissues.

Scaffold-free process does not use hydrogels. It instead mimics cellular self-assembly mechanisms, where cells are first formed into neotissues (new tissues). The resulting tissues are then layered in specific patterns where they join to form larger functioning tissues.

For example: If you want to print a meniscus – a disk of cartilage that cushions the shinbones and thighbones, you would need a healthy supply of chondrocytes for your bioink. You can get these cells either from your donors whose cells have been replicated in a lab, or from your own tissue to create a personalized meniscus which your body would less likely reject.

Bioprinting techniques, and limitations

There are inkjet-based, droplet-based, laser-based, and extrusion based bioprinting techniques. Of these, the most common is the extrusion-based method. The process utilizes a simple setup, where bioink materials are loaded into a printing chamber and pushed through a micronozzle tip.

Using computer to guide, it can precisely deposit the filaments into a desired structure until it stabilizes. If successful, the cells in the synthetic tissue will start behaving the same way cells do in real tissue – communicating, exchanging nutrients and multiplying.

Extrusion-based technique offers relatively better structural integrity because of its precise and accurate deposition of filaments. However, some of its limitations are:

• Some bioinks tend to solidify immediately at the nozzle without successful deposition. When it happens, the process requires UV crosslinkings, or an additional chemical or physical process.
• It may also destroy a significant percent of cells if the tip is less than 400 microns in diameter, or if the inks are dispensed at high pressure.
• Lack of oxygen and nutrients supply to all the cells in a full-size organ.

The hydrogel – cell affair in bioprinting

Bioprinting aims at reducing cell genocide and increasing cell-to-cell interactions, throughout the process. This is only achievable through the use of hydrogels – the material most suited for cell support.

There are many types of hydrogels that offer great possibilities for tissue engineering. However, only a few have been adopted in bioprinting simply because they are not good enough. Even for the selected few, there are several shortcomings:

1. They lack specific ECM (extracellular matrix) proteins for particular cell types; hence, they cannot provide a native environment.
2. They encase cells, which limits their interactions.
3. Same cell density cannot be achieved inside hydrogels as can be in native tissues.
4. Although increased concentration of hydrogels improves mechanical properties, it restricts biological activities.
5. Higher concentration of hydrogels lowers cell mobility, which negatively affects cell growth and deposition of proteins.

Recreating the complex biochemical environment of an organ is too big a challenge for our current technology.  This is the reason our accomplishments so far have been with flat or hollow structures, and researchers are busy looking for ways to incorporate blood vessels into bioprinted tissue.

Can we bioprint a heart?

Researchers have created a functioning piece of heart tissue in the lab (cardiac patch) and successfully demonstrated in vivo its ability to regenerate. But, bioprinting the entire structure still remains a mere scientific imagination.

Because the technology advanced enough to fabricate the heart’s highly complex vascular network is still far from reach. And to make matters worst – unlike other organs, the heart needs substantial vascularization owing to its frantic metabolic activity.

We have already 3D bioprinted implantable meniscus, bladders, and tissues that promote facial nerve regeneration in rats. Lung tissue, skin, and cartilage, as well as miniature, semi-functional versions of kidneys, and livers have also been created using the technology.

And thanks to its great benefit in spatial structuring of cells, bioprinting is now a game-changer in healthcare industry. As the technology continues to make progress, who knows perhaps can we engineer ourselves to give superhuman ability.