BACKGROUND
an overview of the intricate process of bioprinting.
Bioprinting is a form of 3D additive manufacturing that uses cells and other biocompatible materials, such as bioinks, to print living structures for reconstructive purposes. This form of printing has revolutionized regenerative medicine and its applications has led to immense innovation in the field of disease and drug development. There are different types of fabrication techniques when it comes to bioprinting which includes laser-based, extrusion-based and inkjet-based bioprinting. The process principally involves preparation, printing, maturation, and application. This can be summarized in the following three key steps:
Pre-Bioprinting
Pre-bioprinting involves creating a digital file for the printer to read. These files can be created using technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) scans.
Post-Bioprinting
Post-bioprinting is the mechanical and chemical stimulation of the printed parts, where the construct is crosslinked to become fully stable, by either treating it with ionic solution or UV light. The type of crosslinking used is entirely dependent on the construct’s composition. Then, the cell-filled constructs are placed inside an incubator for cultivation.
STEP BY STEP PROCESS.
A digital 3D model is developed by converting medical imaging samples to STL files. Then, the STL file is converted to a gcode file, which is then interpreted into motor movements by the bioprinter. Print parameters are also determined during this stage, which include layer height, nozzle speed, printing speed, needle profile, and many other factors such as pressure & temperature levels.
Stem cells or any other choice of cell line are collected from a biopsy of a host and are put into a growth medium to be cultured into many millions of cells.
The cell aggregates are used to form a bioink and the bioink is then loaded into cartridges that consist of a syringe fitted with a long extrusion nozzle for printing.
Software drives the bioprinter to deposit a pattern of cell aggregates in precise layers, one on top of the other, and interspersed with layers of a water-based substance called a hydrogel, which is deposited by a separate nozzle and functions as a temporary mould around the cells. As layers are built upon, the spheroids naturally fuse together.
The assembled 3D constructs are physically, chemically, and/or biochemically crosslinked to become more structurally stable. The structure may also be cured by UV light or other solutions depending on its composition. Then, the cell-filled constructs are placed inside the growth medium for it to grow and mature. During this stage, the hydrogel is also removed.
After the maturation stage is complete, the printed construct may be used for a variety of medical purposes, whether it be transplants, case studies, clinical trials, or general research.
BIOPRINTING TYPES.
Inkjet-based Bioprinting:
Inkjet-based bioprinting is a non-contact printing technique in which droplets of dilute solutions are dispensed, driven by thermal, piezoelectric, or microvalve processes. Inkjet bioprinting technology is based on the conventional inkjet process used by desktop inkjet printers, whereby individual droplets are used to pattern a substrate. A structure is formed by continuously depositing droplets at predesigned points, enabling a structure with irregular shapes to be fabricated easily. Collectively, inkjet printing has great potential in tissue engineering and regenerative medicine.
Extrusion Bioprinting:
Extrusion bioprinting is the most commonly used printing technique and was developed by Scott Crump in the early 1980s and commercialized by his company Stratasys Ltd. An ink is extruded through a printhead to build a 3D shape in a layer-by-layer manner. Extrusion bioprinting is driven by piston, screw, or pneumatic pressure mechanisms.The main advantage of this technique is the ability to print very high cell densities with a fast fabrication rate. This technique provides excellent structural integrity due to the continuous deposition of the bioink.
Laser-based Bioprinting:
Laser-assisted bioprinting (LAB) is a scaffold-free technique that was initially developed in the mid-80s to deposit metal.The apparatus consists of three main parts: (1) a pulsating laser; (2) a donor-slide, to support and propel the printing material; and (3) a receiver-slide, to collect and support the printed material. The technique depends on a laser-induced vaporization effect of a thin layer of gold/titanium that coats the donor-slide. When applied to bioprinting, this technique is able to achieve prints with excellent resolution and cell viability.
