In this month’s AM Focus on Bioprinting—and the eBook edition which will be released on March 1st—we will take a deep dive into the different bioprinting technologies that are commercially available today. Starting with 3dpbm’s map of bioprinting technologies and companies.
When cell cultures went 3D
3D cell culture is an in vitro technique where cells grow in an artificially created environment, which resembles the in vivo environment. This technique stimulates cells to differentiate, proliferate, and migrate by interacting with their three-dimensional surroundings.
Cell culture products include scaffold-based platforms, scaffold-free platforms, hydrogels, bioreactors, microchips or microphysiological systems (MPS), 3D bioprinting, organoids, and custom services. Scaffold-based platforms are further segmented into macro-porous, micro-porous, nano-porous, and solid scaffolds.
In 3D porous scaffolds, cells grow inside the pores of engineered scaffolds, or into naturally derived fibrous material such as collagen or laminin. Commercialized scaffold-based products that facilitate 3D cell culture consist either in matrices/hydrogels that are extracted directly from animal tissues or secreted by cultured cells. Scaffolds can also be made of different pore sizes in polystyrene or engineered carrier beads, where cells grow either as a monolayer on the outside or on the inside pores in a more three-dimensional configuration.
Cells can also form multi-cellular structures without the support of a scaffold, either on their own (for example spheroids and organoids) or using bioassembly technologies. Commercialized scaffold-free based products consist essentially in platforms that facilitate the formation and screening of spheroids. Spheroids are self-organized clusters of cells.
An organoid is a miniaturized and simplified 3D version of an organ produced in vitro in three dimensions that shows realistic micro-anatomy. They are derived from one or a few cells from a tissue, embryonic stem cells, or induced pluripotent stem cells, which can self-organize in three-dimensional culture owing to their self-renewal and differentiation capabilities.
When assembling cellular microchips (organ on a chip) or MPS, cells are placed inside micro-chip compartments to form cellular micro-environments of higher structural complexity resembling organs. These can be also described as in vitro organ constructs. Cells can also be embedded in 3D gels of the extracellular matrix, called hydrogels, and often used with 3D bioprinting or electrospinning hardware.
Bioreactors are hollow cylindrical chambers that locally control factors such as perfusion, temperature, humidity, and gas exchange. Cells are placed in scaffolds inside those bioreactors to facilitate 3D cell culture.
Enter 3D bioprinting
All the products described above are related to 3D bioprinting, which can be described as a technology that utilizes digital, additive manufacturing techniques to combine cells, growth factors, and biomaterials in order to fabricate biomedical parts that imitate natural tissue characteristics.
The idea of 3D bioprinting can be dated as far back as 1938 when Nobel Prize winner Alexis Carrel and Charles Limberg published The Culture of Organs. However, since its conception, the field was stagnant because the technology simply did not exist (21). There was no way to culture living cells in sufficient quantities, design and ensure the quality of biocompatible materials, or meet the vascularization requirements of tissue cultures. Through a combination of smarter biomaterials, superior designs, and the advent of the 3D bioprinter, many of these hurdles have now been overcome.
The emergence of 3D bioprinting technology has led to the development of 3D in vitro models of human cells or tissue for use in regenerative medicine and tissue engineering. Today 3D printing is used to manufacture precision and personalized pharmaceuticals, as well as medical devices, such as prosthetic limbs, orthopedic and dental implants, surgical instruments, and medical education models.