What is a bioink?

A bioink is any natural or synthetic polymer which has been selected for its biocompatible components and favorable rheological properties. A bioink will typically support living cells, and its characteristics aids cell adhesion, cell proliferation and cell differentiation during maturation. 

Specific bioink formulations are often dictated by the cell type they’re intended to be used with. This is due to the unique needs of different cell types, including the necessary nutrients, growth factors, and physical characteristics that enable the cells to thrive and function. The aim of a bioink is not only to maintain cell viability but also to promote the formation of tissue-specific extracellular matrices (ECMs). 

3D Cell Culture and bioinks

The field of 3D cell culture has been revolutionized by the development and use of bioinks. These specially formulated biomaterials play a critical role in the creation of 3D cell structures and have far-reaching implications for a range of biological and medical applications. However, the impact of different bioink formulations on 3D cell culture can vary significantly, and it’s crucial to understand how these unique formulations can affect specific applications.

At their core, bioinks are material substances infused with live cells that, when deployed in a bioprinter, allow for the construction of three-dimensional structures mimicking natural tissues. These biomaterials are crucial to the successes of 3D cell culture, and their formulation can greatly influence the overall results of this process.

Essentially, a bioink’s formulation is the key factor that determines its biological, mechanical, and physical properties. Understanding the interplay between these properties and the biological environment allows for more successful 3D cell culture applications. 

How bioink formulation affects 3D cell culture results

There are three primary ways in which the formulation of a bioink can affect the success and results of a 3D cell culture: 

  1. Cell Viability:

    The primary purpose of bioinks is to support the growth and proliferation of cells. The formulation of the bioink must be conducive to cell survival for the duration of the culture period. It should provide a suitable environment for cells to adhere, grow, and differentiate. The wrong formulation can compromise cell viability, resulting in unsuccessful cell cultures.
  2. Structural Integrity:

    Bioinks must be formulated to maintain the 3D structure during and after printing. This involves a careful balance of mechanical properties to ensure the bioink has the necessary strength and flexibility. If the formulation is not optimized for this, the printed structure could collapse or deform, hindering the success of the 3D cell culture.
  3. Biocompatibility:

    The formulation of a bioink should be biocompatible, causing no adverse reaction when interacting with living cells or the body. This includes being non-toxic and non-inflammatory. If the formulation lacks biocompatibility, it can cause an immune response or toxicity, which would jeopardize the 3D cell culture’s success.

Given these factors, it’s clear that the formulation of bioinks plays a critical role in the success of 3D cell cultures. Different applications require different bioink formulations, so it’s essential to tailor the bioink to the specific needs of each application.

Considerations when developing a bioink

Optimizing and developing a bioink formulation requires a balance between a number of different factors:

  • Cell viability – the ability for the cells to survive and thrive within the ink
  • Printability – how the bioink can be effectively used in a 3D bioprinter
  • Mechanical properties of the printed structure – which should, ideally, mimic the natural tissue to support proper cell function

One of the key considerations when developing and using bioinks is the choice of biomaterials. Standardized biomaterials or base materials are often used as the foundation for bioink formulations. These base materials provide the structural support necessary for 3D cell structures, ensuring their stability and integrity. 

If you are developing a cell- or tissue-specific bioink, you must balance the needs of the specific tissue you are emulating with the printability of the ink. In short, the bioink must have the right microstructures, ECM or extracellular matrix components, and mechanical characteristics.

The importance of standardized base materials

It is essential to understand that bioinks are not stand-alone substances. Instead, they are complex mixtures composed of various components, amongst which standardized base materials are the most critical. 

These base materials provide the necessary consistency, reliability, and functionality that are vital for the successful creation and application of bioinks.

Here are a few of the more commonly used base materials and their basic characteristics:

Alginate: A plant-based biomaterial with excellent biocompatibility and mechanical properties. It has great versatility within tissue engineering while providing support for cell encapsulation.

GelMA: A modified form of gelatin, and a natural, biocompatible and biodegradable material. It is easily tunable, photo-crosslinkable, and greatly supports cell adhesion and viability. It’s a versatile material for use with multiple cell types and application.

Collagen: A protein naturally found in the bodies of animals, it plays a crucial role in various tissues and organs. It’s known for its biological compatibility and support for cell adhesion, proliferation, and differentiation, as well as its tunable mechanical properties.

Of course, there are a multitude of base materials as well as versions of each materials. To get a better view of important base materials for bioinks, as well as the options you have to choose from, you can browse our catalogue here.

Types of bioinks

When delving into the realm of bioinks, one is likely to encounter two primary categories: synthetic and natural. The choice between these two types is deeply influenced by the specific requirements of the bioprinting process, the desired properties of the final product, and the biological compatibility with the living cells.

Synthetic bioinks

Synthetic bioinks are essentially engineered materials, designed to have precise control over their chemical and physical properties. Examples include polyethylene glycol (PEG), polylactic acid (PLA), and polycaprolactone (PCL).

ParametersSynthetic Bioinks
BiocompatibilityMay require additional processing or modification
MechanicalTunable and often superior
CellularMay require the incorporation of biological cues
PrintabilityHighly controllable due to engineered nature

Natural bioinks

Natural bioinks, on the other hand, are derived from biological sources. Some examples include collagen, gelatin, alginate, fibrin, and hyaluronic acid. These bioinks are inherently biocompatible and often have built-in biological cues to promote cellular interactions.

ParametersNatural Bioinks
BiocompatibilityInherently biocompatible due to their natural origin
MechanicalGenerally weaker and less predictable
CellularNative biological cues present, promoting cell adhesion and proliferation
PrintabilityMay be challenging due to variability in natural materials

Animal-free bioinks

While synthetic bioinks and natural bioinks are one way to look at bioinks, bioprinting is often tauted as a pathway to reduced use of animals in research. 

As such, there’s often a desire to consider bioinks with materials which aren’t sourced from animals. While it is easy to look the way of synthetic bioinks, finding (or synthesizing) a biomaterial which will emulate a tissue is difficult, and natural bioinks are often looked to. To avoid animal use, often plant-based and synthetic materials are used. This minimizes the ethical considerations of using animals while still providing the need for a suitable 3D cell culture environment for cellular growth and function.

Finding the right bioink for you

To truly capture native cell biology we develop biomaterials that have all the biological cues needed.

Whether it is ECM components that drive stem cell differentiation, or biomechanical properties supporting cardiomyocyte functionality. No matter the cell type, or application, our team has a solution.

Bioink Selector Guide

With the variety of bioinks available today, selecting one that best suits your specific needs can be a challenge. To aid you in this process, we have developed a bioink selector guide. This interactive tool will ask you a series of questions about your bioprinting needs, and based on your responses, recommend a bioink that is most likely to help you achieve your desired results. 

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