3D Bioprinting — Could we ever 3D print a fully compatible organ and transplant it?

Key facts about 3D Bioprinting

  • 3D bioprinting consists of adapting the 3D printing technology to print tissue-mimicking constructs.
  • What drives this technology is to print human tissues and organs that can be used to replace our damaged ones.
  • The main problem at the moment is to ensure that these bioconstructions remain alive and functional once printed.

Description

Bioprinting is the merge of two technologies: 3d printing and cell biology. This fast-growing emerging technology has open many possibilities in the field of regenerative medicine and tissue engineering.

This variation of the 3D printing technology uses bio-inks to create biological structures. The main purpose of this technology is to combine cells, growth factors, and biomaterials to fabricate tissue-like constructs that can later be used for clinical and biomedical applications.

A broad range of biomaterials has already been printed. The key is bio-inks.

Bio-inks are mainly cells embedded in a gel-like scaffold. This substrate, which may be organic or synthetic in nature, provides support for the cells to adhere and grow.

How works?

In general terms, bioprinting work very similar to the normal 3D printing. It consists of three steps, pre-processing, printing and post-processing.

First, the desired structure is defined in a digital model. Normally, the geometry to be bioprinted is reconstructed from computer tomographies or magnetic resonance images (MRI).

Second, the object is printed by depositing layers of biomaterial following the digital model.

Third, post-processing usually involves placing the bioprint in a special chamber so that the cells can mature properly and become a functional tissue. This step is, in fact, the main difference from normal 3D printing. Bioprints are living structures, which means that cells need a proper environment with oxygen, nutrients and space for waste disposal.

Printing techniques

Currently, there are several techniques to deposit these cell-rich bio-inks. Each technique is more appropriate for certain types of biomaterials than for others.

Inkjet bioprinting acts similarly to a common office inkjet printer. The bio-ink is pushed through nozzles in a continuous or drop-on-demand manner. The amount of bio-ink deposited in the substrate is controlled by heat or vibration. These bioprinters are more affordable than other techniques but are limited to low-viscosity bio-inks.

Extrusion bioprinting uses pressure to force the biomaterial to flow out of a nozzle. This technique has two advantages. First, bio-inks of different viscosities can be printed by adjusting the pressure, which means that highly viscous hydrogels can be printed without the need for high temperatures. Second, the technique can likely be scaled up for manufacturing, although may not be as precise as other techniques.

Microvalve bioprinting has similarities with the inkjet and extrusion techniques. Biomaterial stored under constant pneumatic pressure is delivered in droplets by the opening and closing of a mechanically, electrically or magnetically controlled microvalve. The printing process can be continuous or drop by drop and works well with low viscosity bio-inks.

Laser-assisted bioprinting moves cells from a solution onto a surface with the help of a laser. The laser heats a specific part of the solution creating a bubble that guides cells towards the surface. This technique is very precise and can be used for highly viscous biomaterials. The problem is that the heat from the laser may damage the cells. Furthermore, the technique is difficult to scale up to print large quantities thus has not been explored extensively as a biofabrication approach.

Tissue fragment bioprinting leverage the intrinsic capacity of closely spaced tissue fragments to fuse together, known as tissue fluidity. Therefore, tissue fragments containing several thousand cells are deposited in close spatial arrays so that they self-assemble.

Here, only the most relevant techniques are mentioned, but in this fast-growing field, new approaches are continuously being tested.

Potential applications

Printing tissues and organs has more applications than you can imagine at first glance.

Healthcare

With the increase in life expectancy and raise in chronic illnesses, exist an enormous gap between organ demand and supply.

One of the promising applications of this technology is the ability to 3D print tissues and organs to replace our damaged ones. The advantage of this method is that it reduces the risk of rejection since the transplantable bioprinted organ will be created form our own cells.

For now, relatively homogenous tissues like cartilage, skin, blood vessels, vagina, urine tubes and bladder have been bioprinted and transplanted in the lab or in clinical trials, but as the technology matures more complex organs are expected to be manufactured.

Also, the living bioprinted materials can be used in tissue engineering and regenerative medicine not only to replace damaged tissues but also to improve biological functions, as is the case with CRISPR technology.

Drug discovery and product testing

Another potential use of bioprinted living materials is in the area of medical testing and drug discovery.

Bioprinted tissues simulate their native microenvironments, such as cell type and tissue microstructure. Thus, bioprints are a good alternative for in-vitro model testing for preclinical test of drugs and cosmetics.

It is foreseeable that this application will be used on a commercial scale prior to organ transplantation as the requirements are lower than the characteristics necessary for its use in the human body.

Skin bioprinting is one of the most promising examples of bioprinting for several applications, such as the development of topical drugs, wound healing studies, and dermal toxicology research.

History and future

Bioprinting technology is the result of advances in many fields, from computing to printing and cell biology. It is difficult to determine a specific date for the birth of this technology although it would be relevant to highlight two important basic advances for this technology: the discovery of stem cells in 1978 and the invention of the 3D printer in 1984.

During the 1990s, medical researchers began to show interest in the idea of printing biological structures.

In 1999, the first lab-grown organ was implanted. The bladder cells were grown on a synthetic scaffold.

Since then, the medical field has begun to develop the bioprinting technology thanks to the advances in 3D printing and cell biology.

Future

There is a huge gap between the demand and the supply of organs for transplantation. This technology is hope for solving this problem. The goal is to print the organs and transplant them in a few hours, without rejection from the body. These printed organs will be created from the same cells of the body of the person being transplanted, matching the exact size, specifications and requirements of each individual patient.

At present, fully functional 3D bioprinted complex internal organs are not feasible, but at the rate of current progress in the field, it could be possible in 10 years.

Controversies

3D bioprinting opens new avenues in the field of personalized medicine. It is a promising technology that can finish the problems of finding a compatible donor. There are no surgical challenges, only technological ones.

Real organs

One thing is to print a tissue structure with the shape of an organ and other is make the organ fully functional. Organs are quite complex structures, they have multiple cell types, blood vessels, nerves, filtration system, and they are strong and durable.

For now, researchers have been able to bioprint many different tissues and organs, but not so many survive more than a few days. There is an urgent need to developed innovative solutions for the vascular networks that provide cells with nutrients and oxygen to grow and develop.

Bioprinting techniques and bio-inks

The current bioprinting techniques have still many limitations. Only certain types of bio-inks can be printed with a limited range of viscosities and limited precision.

In addition, the printing process has the potential to damage cells, as they only thrive within a narrow range of temperature, pressure and oxygen level.

This is a very young technology in rapid development. In the coming years, we will see how all these problems are solved.

4D bioprinting

The next step in this field is to print tissue with the ability to respond to stimuli, for example, heat or pressure, know as 4D bioprinting.

The changes can be in shape, such as deforming, twisting or growing or in function, such as cell differentiation or change in cell polarity.

This is the future indeed. Now, the 3D bioprinted objects are very basic, but we are starting to create more sophisticated multimaterial, multimodal biostructures.

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Now it is your turn.

  • Would you accept a 3D bioprinted transplant?
  • What do you think about bioprinting tissues and organs for drug testing?

Leave us your opinion in the comments.

Links

  1. Biofabrication: an overview of the approaches used for printing of living cells — Scientific study
  2. 3D bioprinting of tissues and organs for regenerative medicine — Scientific study
  3. 3D bioprinting of organs — Youtube video