The future of bioprinting is just around the corner. 3D Bioprinting has been transforming the way we think about regenerative medicine and tissue engineering because of its potential to be a cost-effective means of producing custom human tissues and organs for transplantation or other medical needs. It has taken a leap in recent years, with promising results and bioinks being at the center of it all.
The bioinks used in 3D Bioprinting are the “secret sauce” of this emerging technology. They come in different types and from numerous sources but have one primary goal: to provide an environment for cells to survive and grow.
This blog will provide an overview of what bioinks are, why they’re important in bioprinting, and how they differ. Scientists use bioink, as a carrier material for cells, which act as building blocks for tissues grown in the lab.
The concept of a bioink can be easily understood by the following analogy. Just like how a conventional 2D office printer uses ink cartridges to print on a sheet of paper, a 3D bioprinter requires a bioink to print 3D constructs, scaffolds (building blocks of bioprinted tissues). A bioink very simply put is a mixture of cells, biomaterials, growth factors, and nutrients.
The biomaterials used in the bioink composition are chosen based on the cell type of interest. These biomaterials are primary components of the ECM (Extracellular Matrix) of the tissue that we intend to bioprint.
Scientists have been using natural or synthetic polymers to print materials for many years. However, there are significant challenges in creating a functional bioink. Natural polymers are rigid and short-lived, and synthetic polymers do not mimic the natural ECM of living tissues. Cells cultured in these environments have a poor survival rate and fail to thrive.
Layers or droplets of bioinks can be extruded from various bioprinters based on the purpose of the construct being printed. For example, droplets of bioink can be extruded from a bioprinter to create a 3D bioprinted scaffold, used to study the effect of mechanical stress on cells, which can then be used in the construction of tissue.
For cells to survive and thrive in a 3D bioprinted construct, it is vital to have an effective bioink. Researchers are experimenting with different types of bioinks that are compatible with different types of 3D bioprinting technologies.
Aqueous Bioinks
Aqueous-based bioinks are one type that is gaining momentum in the cellular engineering field. They consist of a hydrogel base containing nutrients and naturally occurring materials that support cellular growth. Many are printed from bioprinters. Pellets or droplets of aqueous-based bioinks are extruded to create scaffolds for tissue engineering. The hydrogel in this type of bioink provides a substrate for cells and polymers act as signaling molecules to promote cell differentiation and proliferation. One major advantage of this bioink is that its temperature can be easily regulated, which is important for controlling the proliferation of cells. Another advantage is that since it’s easy to print, multiple copies can be made quickly and with little effort. Various research groups are working on different types of aqueous bioinks with variable properties, including those that can be easily biodegradable.
Non-Aqueous Bioinks
Non-aqueous bioinks are an alternative to aqueous bioinks that have all the same functions as their counterparts. However, they provide environments with different properties than aqueous bioinks providing benefits for printing cellular structures with specific material properties. One type is polyethylene oxide (PEO) based which consists of a hydrophilic polymer that is soluble in water. The hydrogel base creates stable structures for cell culture and the PEO polymers have many signaling functions, such as cell proliferation and differentiation.
When choosing the perfect bioink that is both cell-friendly as well as suitable for bioprinting, one needs to consider several factors.
Firstly, the bioink should be cytocompatible and provide an ideal environment for the cells. The cells should be able to attach, proliferate and migrate once they are printed into 3D scaffolds. It is very important for transplantable 3D bioprinted constructs that the bioink should not cause any immune or inflammatory response after it is transplanted.
Secondly, the bioink should be “printable”, it should possess optimal rheological and mechanical properties suitable for bioprinting. An important aspect to focus on here is the shear thinning and viscoelastic nature of the bioink. They aid in bioprinting of uniform lines without breakage which translates into a uniform 3D bioprinted scaffold.
Thirdly, the bioink should protect the cells from shear stress experienced during the bioprinting process. This is especially true for bioinks used in pneumatic and inkjet based bioprinting approaches. The pressure developed within the bioink chamber during the extrusion process can lead to cell breakage and cell death. The bioink protects the cells by providing adequate cushioning.
Fourthly, the bioink should be paired with a suitable crosslinker that does not cause cytotoxicity. Also, helps in maintaining the shape fidelity of the bioprinted construct after bioprinting. Once the bioink is printed and crosslinked, the microporosity of the scaffold should not restrict the movement of the cells; this could lead to cell death due to lack of contact with other cells.
The fifth and most important consideration being the degradation of the scaffold. The bioink should support cell growth until the cells can form their own ECM(extracellular matrix), after which it should be easily degraded by the cells.
Bioinks play a vital role in any 3D Bioprinting setup and are as diverse as the technologies available in 3D Bioprinting. You can learn more about this on our Foundation Course on 3D Bioprinting, where we cover the intricate nature of bioinks and biomaterials in depth. The type of biomaterials used to form these bioinks will vary depending on the type of target tissue for the bioprinting protocol. Globally, many private and academic establishments are working to develop bioinks for clinical applications. Bioink research is just beginning to find its roots in the clinical translation of 3D Bioprinting. Looking at the current research trends and industry requirements, the future of bioink research will see a giant leap over the next few years.
Authors
Pooja Venkatesh
Pooja is the Co-CEO and Co-Founder of NBIL. Pooja is a Masters graduate in management specialising in strategy from CASS Business School, London, with a Bachelor’s degree in biotechnology. Pooja brings a perfect blend of business acumen and technical expertise to the NBIL team. She currently heads the biotech research and development at NBIL and is also overseeing the IP and Regulatory Affairs of the Company.
Anubha Mehra
Anubha handles marketing, IP and regulatory activities within Next Big Innovation Labs. She is an experienced marketeer who focusses on building customer oriented marketing strategies for biotech led enterprises. Working on the IP and regulatory aspects of NBIL, Anubha understands the various nuances involved in building and marketing patentable and innovative products.
