3D Bioprinting

Title of project: 3D Bioprinting

Cluster: Biomed

Technology Tags or Keywords: 3D Bioprinting, biofabrication, additive manufacturing, regenerative medicine, cell biology, 3D structures, hydrogels

Title: 3D Bioprinting technology using 3D Bioprinter FABION

Summary:

In general, 3D printing (often called additive manufacturing or direct digital manufacturing) is a process, where some three-dimensional object is created (prototyped) by a printer using any needed material as the “ink” and directed by a computer aided design (CAD) file based on a 3D modelling program (created either from scratch or by scanning a 3D model to be reproduced).
Accordingly, 3D bioprinting (or tissue, organ construct, or organ printing) is an automated and computerised process of layer-by-layer printing of 3D animal or human tissues, organ constructs or whole organs by using cells or tissue spheroids (cell aggregates) as bioink and using biodegradable hydrogels, holding cells or spheroids in place and providing a nutritional environment, as biopaper.
Naturally, 3D bioprinting requires special printers (3D bioprinters) that dispense bioink and biopaper with high precision according to the instructions received from CAD. Subsequently, the printed tissue/organ construct may be placed in a bioreactor, a mechanical unit creating a biological environment necessary for tissue/organ construct’s growth and development.

Technology Benefits :

3D Bioprinting is a high automated and standartized technology. With its potential to eventually print fully functioning human organs (or, in the nearer perspective, to manufacture efficient organ constructs, grafts or patches), 3D bioprinting represents the best economical and viable opportunity to close the gap between the limited number of donated organs available for transplantation at any given time, on one hand, and the long waiting list of potential recipients, whose very survival, or at least quality of life, depend on timely receiving a needed match, on the other hand. Moreover, made out of the patient’s own cells, such a transplant will potentially eliminate the danger of organ rejection without any need for immunosuppressant drugs. Saving millions of lives, this fast, precise, and efficient way of manufacturing transplants on demand will be one of the most important scientific breakthroughs in human history.
Already, 3D printed organ constructs offer a much more efficient way to test prospective drugs, allowing drug manufacturers to save time and millions of dollars in costs wasted on dead-end drugs that eventually fail in clinical trials (while animal testing results do not necessarily translate into human body reaction to the same drug). In terms of personalized healthcare, printed organ constructs using patient’s own cells allow testing the effects of a complex combination of various drugs on that specific patient.
It must also be noted that, for the cosmetic industry, testing its products on 3D printed organ constructs may not only be more efficient but may represent the only way to conduct tests, as animal testing of cosmetic products is already banned in many countries.
By the same token, 3D bioprinting hugely advances disease modeling in search of potential treatment and will allow a personalized treatment approach tailored precisely for an individual patient.

Technology Applications :

3D printing in general - with infinite customization, no need for economies of scale to make manufacturing cost effective, and the ability to produce anything when and where needed - has already revolutionized the way things are made, and is widely adopted by a vast range of industries: from auto manufacturing and aerospace to jewelry and crafts.
While in the healthcare industry, 3D printing is already successfully used to manufacture prosthetics, hearing aids, dental implants, and medical instruments, 3D bioprinting (3D printing using living cells) is still in a relatively early stage of development. However, once the 3D bioprinting industry matures, it will certainly revolutionize healthcare as we know it.
Bioprinted tissue and organ constructs for drug testing and discovery are the first practical applications of 3D bioprinting; the other potential fields being disease modeling, and finally – treatment. Certainly, the enormous promise of manufacturing fully functional human organs for transplantation is the industry’s ultimate goal.
Bioprinting technology can also be used for industrial-scale environmentally friendly production of meat, leather and fur without killing animals, as currently practiced by the conventional farming, food and fashion industry.

It is commonly expected that the 3D bioprinting market having an extraordinary growth potential will evolve into a multibillion-dollar industry within the next 10-15 years.

Detailed Technology Description:

Bioprinting technology consists of 3 sequental stages: 1)Preprocessing:creating a digital model of the construct; 2)Processing: bioprinting process itself with dispensing "bioink" - cells or tissue spheroids and "biopaper" - hydrogels which are serve as a temporary scaffold; 3)Postprocessing - maturation of the bioprinted construct or/and its transplantation into the organism. A very important element of our 3D bioprinting technology is using tissue spheroids as bioink. Tissue spheroids serve as building blocks, and printing with different types of spheroids allows the fabrication of functional tissue and organ constructs. The underlying scientific basis is the natural ability of spheroids to fuse or self-assemble driven by the force of surface tension.
Additionally, tissue spheroids have some other remarkable attributes: a very high cells density (normally characteristic of natural tissues), their ability to produce extracellular matrix, and the capability to be spread on an adhesive surface. Printing with spheroids significantly increases the speed of the process of 3D bioprinting. All these qualities make tissue spheroids a very attractive raw material for tissue engineering in generally and for 3D bioprinting in particular.

Bioprinter FABION

Unveiled by our Moscow, Russia-based subsidiary, 3D Bioprinting Solutions, in September of 2014, the originally designed FABION bioprinter allows precise layer-by-layer deployment of tissue spheroids (bioink) in hydrogel (biopaper) using a programmed digital model. The printing of spheroid layers, which may differ from each other, continues for the programmed number of times until the final layer is printed. This procedure allows creating live and functional 3D tissue and organ constructs with a complex structure.

Due to its unique design and proprietary engineering solutions developed by 3D Bioprinting Solutions, FABION is a truly universal tool for printing live and functional 3D tissue and organ constructs.

FABION is superior to other commercially available bioprinters in many respects:

Multifunctionality: FABION allows printing with a wide range of hydrogels, using different types of polymerization (temperature, ionic, chemical, pH, etc.)
Safety: A unique UV tool for hydrogel (biopaper) polymerization does not contact with spheroids or cells and, consequently, does not damage their DNA.
Flexibility: FABION allows combining different methods of bioprinting, methods of application, and materials. Further enhancing the equipment’s flexibility is a wide range of programmable and software controlled parameters of bioprinting.
Precision: FABION’s resolution meets the highest standards in bioprinting.
Laser calibration system: Х-Y-Z positioning system has a feedback feature allowing the bioprinter’s nozzle positioning accuracy of 5 micrometers, thus ensuring a very precise reproduction of the programmed digital model.
Compactness: Г-shaped design of the bioprinter’s printing system allows for sufficient space to accommodate nozzles.
Control: 3D bioprinting is controlled in the real time mode with the help of an in-built digital camera.

FABION has a total of 5 nozzles with programmable capacity to dispense different types of bioink and biopaper. Three nozzles dispense bioink, and spheroids of any type or size, and various cells suspensions or other materials may be loaded into each of these three nozzles. The system allows setting the number of tissue spheroids to be dispensed, the thickness of printed layer, and other printing parameters for each particular nozzle. The other two nozzles are of a different design as they distribute biopaper, which may be applied by pulverisation or by dispensing.

The software developed for the bioprinter allows using different number of nozzles and in different configurations and is compatible with various 3D modelling programs and supports different polygonal modelling file formats. To launch the process of bioprinting, certain parameters are fed into the control software, such as:

Distance between the centers of the spheroids.
Positioning of spheroids in the coordinate grid.
Distances between the positions of the nozzles along X, Y and Z axes and all necessary parameters for the bioprinter’s X-Y-Z positioning system.
Nozzles’ movement sequence (motion of each nozzle loaded with certain material must be set for each cell in the coordinate grid).
Speed.
Volumes of biopaper and bioink to be dispensed.

Additionally, it is possible to enter a broad range of input data, such as, for example, time and intensity of the UV radiation source.