Manufacturing a Personalized Cellular Universe: 3D Bioprinting in the Biotech Industry

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Tissues in the body work as a complex team of interconnected cells. For instance, the heart is comprised of contractile cardiomyocytes, along with a vast array of endothelial cells, immune cells and fibroblasts. Similarly, the liver includes hepatocytes, immune cells, endothelial cells and epithelial cells. Put in all the cellular players, and the team wins. Take out one player, and the team is no longer able to sufficiently function.

The field of 3D bioprinting draws deeply on this idea of optimizing tissue regeneration and replacement. By using naturally-derived scaffolds, human cells and other biocompatible materials, 3D bioprinting has ushered in opportunities for researchers to design, print and optimize patient personalized tissues for purposes ranging from transplantation to drug testing.

“The current drug development process is extremely lengthy and costly due to the lack of proper tools for preclinical drug screening,” said Dr. Wei Zhu, CEO of Allegro 3D, a San Diego-based bioprinting company. “What excites us most about 3D bioprinting is its potential to provide a paradigm shift in the drug discovery and screening process.” 

The bioprinting process is analogous to a Build-A-Bear factory – but while a teddy bear contains carefully chosen ribbons, buttons and stuffing, 3D bioprinting creates complex tissues possibly derived from a patient’s own cells. In both cases, integrating customized components allows for layer-by-layer formation of something unique, yet fully functional.

While the techniques used for 3D bioprinting have mechanical grounding in traditional printing, the defining characteristic of 3D bioprinting is the usage of bioinks. Bioinks are complex, optimized mixtures of solution matrices containing carrier molecules and additional supporting agents. Often, the solution material is a biopolymer – a naturally-derived gel, used to envelop the cells as a 3D molecular scaffold. Common biomaterials include gelatin, hyaluronic acid and alginate, all of which retain a high degree of biocompatibility. They provide a supporting structure, as well as a nurturing environment for future cellular growth and differentiation.

Historically, 3D bioprinting has become possible through three main modalities: light-based bioprinting, inkjet bioprinting and extrusion based bioprinting. Light-based bioprinting utilizes a light source, which can often be a blue LED, to cure photo-polymerizable bioinks into a more solidified scaffold. Inkjet bioprinting, on the other hand, is analogous to the conventional desktop printer, where bioink droplets are positioned on a receiving substrate based on computer control. Finally, extrusion based bioprinting relies on pressure to mechanically dispense bioinks by syringe extrusion onto receiving substrates.  

Each technique has its own unique advantages. For example, light-based bioprinting allows for an incredible degree of precision, resolution and speed – resulting in the possibility of micro or nanopatterning in a rapid fashion. Inkjet or droplet bioprinting is markedly straightforward, with low overall production costs and easy handling. Extrusion-based printing allows for printing with high cell densities.

Allegro 3D finds its niche in the bioprinting industry by providing light-based printing products – primarily, their StemakerTM bioprinter and SteminkTM bioinks. Notably, the StemakerTM bioprinter was the world’s first digital light processing (DLP) bioprinter for high throughput tissue printing. Light is applied to the pre-polymer bioink, which photopolymerizes layer-by-layer to encapsulate live cells in the final 3D tissue construct. By using visible light as the photopolymerization source, cell viability remains very high during the manufacturing process. Furthermore, the technique allows for incorporation of various cell types in a single printed scaffold – for instance, liver cells in the bottom layer, and endothelial cells in the top layer. With the ability to mix and match various cell types, the complexity and diversity of human tissues is an achievable possibility.

In terms of application, the possibilities of Allegro 3D’s bioprinting techniques have dramatic implications for the biomedical community.

“With our StemakerTM bioprinters and SteminkTM bioinks, our customers can print 3D precision human tissues on demand for various biomedical applications,” Zhu said. These applications include “building tissue samples for disease modeling, providing patient-specific tissues or organs for therapeutic treatment of injuries, and providing 3D human tissues to investigate the toxicity and efficacy of new drug compounds in vitro.

By closely mimicking hepatic lobule structure through an eye-catching pattern of hexagons and circles that looks somewhat like a bee’s hive, this DLP bioprinter was able to print human liver tissue containing both human induced pluripotent derived stem cells and other supporting cells in seconds. The goal of such constructs would then be to provide easily accessible tissues for high-throughput drug discovery, or to print patient-derived hepatic tissues for liver regeneration.

According to Zhu, a key issue with traditional bioprinting techniques is that of scalability. Pharmaceutical and biotechnology industries often use high-throughput screening instruments – for which the needs far exceed the capabilities of traditional bioprinters. The photopolymerization techniques of the StemakerTM bioprinter allow for “compatibility with the high-throughput systems, which will greatly help our customers improve the accuracy and efficiency of drug screening and assay development.”

On the extrusion-based bioprinting front, Allevi, a 3D bioprinting company based in Philadelphia, focuses on providing universally-friendly extrusion-based bioprinters, bioinks and software. Their latest model, named Allevi 3, contains three extruders through which bioinks can be deposited to form tissue scaffolds. Allevi also offers a wide selection of bioinks, which can be mixed in conjunction with cell populations to be directly utilized in their 3D bioprinters.

Likewise, Cellink, which was the first company to commercialize bioinks, is a Boston-based bioprinting company that has since expanded to provide services ranging from bioprinters to live cell imaging and liquid handling machines. Cellink’s bioprinters include extrusion-based printers that contain up to six extruder heads with the BIO X6, as well as light-based printers. Their vast array of automated systems represents a diverse amalgamation of capabilities for more streamlined manufacturing.

Altogether, these 3D bioprinting companies represent a rapidly growing sector of the biotechnology industry. The unmet medical need of human tissue for regeneration, drug testing, and other pharmaceutical purposes remains a key driving force. 3D bioprinting has potential to change the ways in which we discover new, exciting chemical compounds to treat debilitating diseases, or to eliminate the strenuous waiting game experienced by many in need of an organ transplant. With the advent of these technologies, we acknowledge a future where we may potentially design, print and order complex human tissues for life-saving purposes.

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