It isn’t news for 3D printing to have been made possible in this decade, but nonetheless it is the most exciting technological development that has rocked the bed of medicine and biotechnology. To establish an understanding, three-dimensional (3D) printing is a manufacturing method in which objects are made by fusing or depositing materials—such as plastic, metal, ceramics, powders, liquids, or even living cells—in layers to produce a 3D object .

3D bio-printing technology has been studied by biotechnology firms and academia for possible use in tissue engineering applications in which organs and body parts are built using inkjet techniques. In this process, layers of living cells are deposited onto a gel medium or sugar matrix and slowly built up to form three-dimensional structures In future scientists may be able to build brand new parts of the body from scratch for replacement. The new branch in medicine called Regenerative medicine will enable far reaching advances in medical field with 3D printing. A printable organ, the most exciting development of the technology is an artificially constructed device designed for organ replacement. Some printed organs have already reached clinical implementation, including hollow structures such as the bladder and vascular structures. Research is currently being conducted on artificial heart valves, kidney, and liver structures, that are considerable complex in both structure and function.

3D printing allows for the layer-by-layer construction of a particular organ structure to form a cell scaffold, followed by the process of cell seeding, in which cells of interest are pipetted directly onto the scaffold structure.

Modified inkjet printers filled with a suspension of living cells and a smart gel, have been used to produce three-dimensional biological tissue.

Approaching the printing process for any specific organ is similar to the way you would approach printing a book. The results obtained however, are of course are far more fascinating and bring us as a race, a lot closer to understanding our body and the process that helps us replicate it.

There are five necessary elements involved: a draft, the physical printer itself, a movable type, paper, and ink.

Bioink

The term “bioink” has been used as a broad classification of materials that are compatible with 3D bioprinting. The bioink used in the organ printing is based on the specified organ and patient with regards to unique cells, biomaterials and biochemical signals. There are two categories that make up the bioink process, functional scaffold and scaffold-free. Functional scaffold uses biomaterials that may or may not have cells as the actual ink, while scaffold free uses solely cells. The biomaterials used in the functional scaffold vary from hydrogels to metal implants, single to multiple nanometers in size. The economy and availability of materials is crucial in choice of these materials.

Printers

In bioprinting, there are three major types of printers that have been used. These are inkjet, laser-assisted, and extrusion printers. Inkjet printers are mainly used in bioprinting for fast and large-scale products. One type of inkjet printer, called drop-on-demand inkjet printer, prints materials in exact amounts, minimizing cost and waste. Printers that utilize lasers provide high-resolution printing; however, these printers are often expensive. Extrusion printers print cells layer-by-layer, just like 3D printing to create 3D constructs. In addition to just cells, extrusion printers may also use hydrogels infused with cells.

Printing materials

Materials for 3D printing usually consist of alginate or fibrin polymers that have been integrated with cellular adhesion molecules, which support the physical attachment of cells. Printing materials must be

  • biocompatibile
  • physically and chemically appropriate for cell proliferation.
  • Biodegradable, it insures that the artificially formed structure can be broken down upon successful transplantation, to be replaced by a completely natural cellular structure.

A process for bioprinting organs involves following steps

1) create a blueprint of an organ with its vascular architecture

2) generate a bioprinting process plan

3) isolate stem cells

4) differentiate the stem cells into organ-specific cells

5) prepare bioink reservoirs with organ-specific cells, blood vessel cells, and support medium and load them into the printer

6) bioprint

7) place the bioprinted organ in a bioreactor prior to transplantation.

3D bioprinting is based on three main approaches: Biomimicry, autonomous self-assembly and mini-tissue building blocks.

Biomimicry

The main goal biomimicry of this approach is to create fabricated structures that are identical to the natural structure that are found in the tissues and organs in the human body. Biomimicry requires duplication of the shape, framework, and the microenvironment of the organs and tissues.

Autonomous self-assembly

This approach relies on the physical process of embryonic organ development which then replicates the tissues by using this process as a model. Autonomous self-assembly depends on the cell as the fundamental driver of histogenesis

Mini-tissue

Mini-tissue approach takes the small pieces and arranges them into larger framework.

3D bioprinting generally follows three steps, pre-bioprinting, bioprinting, and post-bioprinting.

Pre-bioprinting

It is the process of creating a model that the printer will later create and choosing the materials that will be used. The first step is to obtain a biopsy of the organ. To print with a layer-by-layer approach, tomographic reconstruction is done on the images. The now-2D images are then sent to the printer. Once the image is created, certain cells are isolated and multiplied. These cells are then mixed with a special liquefied material that provides oxygen and other nutrients to keep them alive .

Bioprinting

In the second step, bio-inks are placed in a printer cartridge and deposited using the patients’ medical scans, bioprinted pre-tissue is transferred to an incubator, this cell-based pre-tissue matures into a tissue, typically involves dispensing cells onto a biocompatible scaffold using a successive layer-by-layer approach to generate tissue-like three-dimensional structures

Post-bioprinting

Creates a stable structure from the biological material. To maintain the object, both mechanical and chemical stimulations are needed. These stimulations send signals to the cells to control the remodeling and growth of tissues. In addition, bioreactor technologies have allowed the rapid maturation of tissues, vascularization of tissues and the ability to survive transplants.

 3D printing has been applied in medicine since the early 2000s, when the technology was first used to make dental implants and prosthetics. Recently published reviews describe the use of 3D printing to produce bones, ears, exoskeletons, windpipes, a jaw bone, eyeglasses, cell cultures, stem cells, blood vessels, vascular networks, tissues, and organs, as well as novel dosage forms and drug delivery devices.

Therapies based on tissue engineering and regenerative medicine are being pursued as a potential solution for the organ donor shortage. The traditional tissue engineering strategy is to isolate stem cells from small tissue samples, mix them with growth factors, multiply them in the laboratory, and seed the cells onto scaffolds that direct cell proliferation and differentiation into functioning tissues.Creating new tissues for medical research to screen therapeutic uses of drugs can cut the cost and time in drug development.

The technology allows production of implants and prostheses, and hearing aids.

Furthermore, the individual variances and complexities of the human body make the use of 3D-printed models ideal for surgical preparation and drug administration, thereby allowing personalized medical care to happen.

Being under development, bioprinting faces a plethora of challenges. Cell proliferation provided by bioprinting is conducted in an artificial environment, which is devoid of natural biological signaling and processes; the lack of these inhibits the development of appropriate cellular morphology and differentiation. When present, these conditions allow the printed organ to more accurately mimic in vivo conditions and adopt the corresponding structure and function, as opposed to growing as a shaped scaffold of cells. Another challenge is the need to vascularize artificial structures for cellular sustainability. Vascular structures, such as blood vessels, along with artificial vascular constructs, allow for the diffusion of key nutrients and oxygen. However, these have not been fully integrated into the technique of bioprinting.

Since 3D printing is a relatively new technology, there is a lot of room for growth.

3D printing with computer aided techniques have allowed for advancements at the cellular level. Currently the idea of fusing living cells with the biomaterials used to create the 3D tissues. The concept of 3D vascular conduits without scaffolding is being developed currently with hopes of being able to be used in congenital heart surgery. In addition branched vascular structures, bile duct, solid organs like liver and kidneys are also being researched. Advancements in robotic bioprinters and robot-assisted surgery may also be integral to the evolution of this technology.

Conclusively, 3D printing has become a useful and potentially transformative tool in a number of different fields, including medicine. As printer performance, resolution, and available materials have increased, so have the applications. Researchers continue to improve existing medical applications that use 3D printing technology and to explore new ones. The medical advances that have been made using 3D printing are already significant and exciting, but some of the more revolutionary applications, such as organ printing, will need time to evolve.

Author: Nikhil More 
Editor: Aastha Munjal
Thumbnail Artwork: tfot
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