3-Dimensional (3D) Bioprinting Technology and Bioprinters

Author

Pharm. Humeyra Betul Yekeler

Department of Pharmacology, Faculty of Pharmacy, Marmara University - Center for Nanotechnology and Biomaterials Application and Research, Marmara University - MecNano Technologies, Cube Incubation, Teknopark Istanbul

"3-dimensional (3D) bioprinting is a promising and rapidly emerging technology with numerous applications, especially in healthcare."

3-Boyutlu (3B) Biyobaskı Teknolojisi ve Biyoyazıcılar

What is 3D bioprinting technology?

3D printing, which has attracted increasing attention in recent years, is called "3D bioprinting" in the healthcare industry because it facilitates the on-demand "printing" of cells, tissues, and organs. 3D bioprinting is a computer-aided technology that involves the rapid layer-by-layer printing of bio-inks mixed with living cells on a substrate or tissue culture dish to create tissue and organ-like 3D structures with the desired cellular architecture. These technological advances have led to the creation of new scientific fields such as "tissue engineering". 3D bioprinting technology is especially important in addressing the medical demands of the aging population, reducing the use of experimental animals, and finding solutions to the problems of patients suffering from organ failure.

Historical development of 3D bioprinting

The history of 3D bioprinting is a relatively recent development that has its roots in the broader field of 3D printing and tissue engineering.

Early 2000s: The concept of 3D printing dates back to the 1980s, but it gained prominence in the early 2000s. The technology allowed for the layer-by-layer deposition of materials to create three-dimensional objects.

Mid-2000s: Tissue engineering, which combines principles of engineering and biology to create functional tissues, began to gain traction. Researchers explored the possibility of using 3D printing techniques for tissue engineering applications.

2003: Scientists at Wake Forest Institute for Regenerative Medicine led by Dr. Anthony Atala successfully printed the first functional human organ, a bladder, using a combination of cells and a biodegradable scaffold. While not directly 3D bioprinting in the modern sense, it laid the foundation for the field.

2009: The term "bioprinting" was coined by Gabor Forgacs and his team at Organovo, a biotechnology company. Organovo focused on using 3D printing to create functional human tissues for pharmaceutical testing.

2010s: The 2010s saw significant advancements in 3D bioprinting technology. Various research groups and companies began experimenting with different methods and materials for printing tissues and organs.

2015: Researchers at Harvard University successfully bioprinted blood vessels. This marked a significant step toward the eventual printing of more complex organs.

2016: Organovo announced the successful bioprinting of functional liver tissue, demonstrating the potential for 3D bioprinting to create more complex and vital organs.

2019: Researchers at Tel Aviv University announced the successful 3D printing of a heart using a patient's cells and biological materials. While the heart was small and not fully functional, it represented a milestone in the quest for 3D-printed organs.

2020s: Research and development in 3D bioprinting continue to progress. Scientists are working on refining techniques, improving the materials used, and exploring new applications, including personalized medicine and transplantation.

Types of 3D bioprinting

3D bioprinting can be performed in various types using different techniques and methods. Commonly known types of 3D bioprinting:

3D extrusion printing: It is the most widely used 3D bioprinting technique. It creates 2D or 3D structures by dispensing endless filaments of material consisting of cells mixed with hydrogel through a micro-nozzle. As well as being affordable, it has many advantages, including the ability to create large-scale structures, high cell density, and the use of a wide range of biomaterials, both synthetic and natural polymers.

Laser-assisted bioprinting: Printing is carried out using laser light, sintering, or polymerizing layers of material to create a specific pattern. This method is used to produce finely detailed textures. It can use high viscosity and solubility bio-ink but causes cell damage due to high laser energy. It also has the disadvantages of high cost and difficulty of use.

Inkjet-based bioprinting: Bioprinting is performed by spraying a jet of liquid containing cells and biomaterial onto a substrate and depositing it in layers. This method is useful for creating tissues with a high cell density. The advantages of inkjet-based bioprinting are high printing speed and low cost, while the disadvantage is the small variety of printable biomaterials.

Stereolithography (SLA) bioprinting: SLA is a process that involves polymerizing a photosensitive resin in layers with laser light. SLA bioprinting technology can be used to produce 3D patterned scaffolds at micro- and nano-sizes but requires high-cost equipment and materials.

Digital light processing (DLP) based bioprinting: DLP enables the construction of 3D objects by rapidly polymerizing 2D layers at high resolution using a setup consisting of a light source and a digital micro-mirror. DLP-based bioprinting is known for its ability to provide high resolution, fast production, and precision. However, the use of carefully selected and optimized materials is necessary due to the photosensitivity of cells and bioinks. Furthermore, it is important to evaluate the biological and mechanical properties of the produced tissue.

Biomaterials for 3D bioprinting

Biomaterials are key elements for bioprinting; they must provide various requirements for tissue engineering, such as biodegradability, biocompatibility, and bioprintability. Biomaterials support the standard biological functions of the cell, such as proliferation, growth, and signaling, thus maintaining the viability of cells. They also help in the formation of microstructures that mimic the natural environment of the cell. Polymers used in biomaterials can be classified as natural polymers, synthetic polymers, or combinations of both.

Natural polymers

Natural polymers for 3D cell culture have properties similar to human extracellular matrix structure to mimic bioactivity. Natural polymers used as bioink sources include alginate, gelatin, collagen, chitosan, agarose, and hyaluronic acid (HA).

Synthetic polymers

Synthetic polymers are excellent sources for bio-ink production due to their specific physical properties. However, synthetic polymers have several disadvantages, such as undergoing uncontrollable degradation and having poor biocompatibility. Polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), polyethylene oxide (PEG), and thermoplastic polyurethane (TPU) are widely used as synthetic polymers for tissue engineering.

3D bioprinting applications

3D bioprinting is used in many fields such as tissue engineering, regenerative medicine, organ and drug printing, toxicology screening, clinical transplantation, high-throughput testing, and cancer research.

Organ and tissue regeneration: 3D bioprinting enables living organs and tissues produced outside the body to be used to replace diseased or damaged tissues. This could offer a promising solution for patients waiting for organ transplantation.

Drug testing and development: 3D bioprinting can be used in the development of in vitro tissue/organ models for drug screening, to study the effects of drugs and accelerate drug development processes. Testing drugs on human tissues can help identify more effective and safer drugs.

Drug delivery systems: 3D printed drug delivery systems have advantages such as the ability to design customized drug products with high flexibility to choose the form, döşe, and size of the dosage form to provide individual patient requirements.

Dental applications: Personalized 3D printing solutions can be developed for dental implants, dentures, and other dental applications.

Ear, nose, and throat (ENT) practices: 3D bioprinting can be used for ENT applications such as personalized ear and nose prostheses, cartilage tissue regeneration, and hearing aids.

Skin regeneration: 3D bioprinting can be used as a treatment for burns, ulcers, or other skin lesions. This could involve the production of personalized skin tissues using the patient's cells.

Cardiovascular applications: 3D bioprinting can be used to reconstruct heart valves, vessels, and other cardiovascular structures. This could offer innovative solutions for treating conditions such as heart disease.

Medical training: 3D bioprinting can be used in surgical training and anatomical model production. Realistic simulation of tissues can improve the training and planning of surgical interventions.

The future of 3D bioprinting

Advances in 3D bioprinting are increasing with the rapid development of technology. Functional bladders grown with tissues bioprinted from patients' cells have already been successfully transplanted into the human body. Scientists are working intensively on the possibility of printing patients' damaged organs using the patient's stem cells or other cells, aiming to reduce the need for organ donors.

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