What is Physical Crosslinking Bioinks?

Physical crosslinking bioinks play a crucial role in the field of bioprinting, a cutting-edge technology that involves the fabrication of three-dimensional structures using biological materials. To understand what physical crosslinking bioinks are, let's break down the key components and processes involved.

At its core, bioprinting is a revolutionary technique that merges principles of biology, engineering, and material science. It allows scientists and researchers to create intricate structures by depositing layers of bioinks, which are bio-compatible materials containing living cells, in a controlled manner. These cells can be sourced from various tissues, including skin, cartilage, or even organs, depending on the intended application.

Different crosslinking methods of bioinks. Figure 1. Different crosslinking methods of bioinks. (Ashammakhi N, et al.; 2019)

Now, physical crosslinking comes into play as a critical aspect of the bioink's composition. Crosslinking refers to the formation of bonds between polymer chains, creating a network that provides structural integrity to the material. In the context of bioprinting, there are two main types of crosslinking: physical and chemical.

Physical crosslinking involves the use of non-covalent interactions to form bonds between polymers. These interactions can include hydrogen bonding, van der Waals forces, or electrostatic interactions. In the case of physical crosslinking bioinks, these interactions are employed to give the material its stability and shape.

One common method of physical crosslinking in bioinks is through the use of temperature changes. This process, known as thermoresponsive gelation, relies on polymers that undergo a phase transition in response to temperature variations. At lower temperatures, the polymer solution is liquid and can be easily extruded through the bioprinter nozzle. However, when the temperature is increased, the polymers undergo a gelation process, forming a solid structure that retains the deposited shape.

Another approach involves using light-sensitive materials. Photo-crosslinking bioinks contain components that react to specific wavelengths of light. When exposed to the appropriate light source, these materials undergo a photochemical reaction, leading to the formation of crosslinks and solidification of the bioink. This method offers precise control over the crosslinking process, allowing researchers to pattern complex structures with high resolution.

The advantage of physical crosslinking lies in its reversibility. Unlike chemical crosslinking, which involves permanent bonds, physical crosslinks can be broken and reformed under certain conditions. This property is particularly valuable in bioprinting because it enables the incorporation of cells into the bioink without compromising their viability. Cells can be mixed with the liquid bioink, and once the printing is complete, the physical crosslinks can be established to hold the structure together.

Moreover, physical crosslinking bioinks are often more biocompatible than their chemically crosslinked counterparts. The absence of harsh chemical reactions reduces the risk of cell damage or toxicity, making these bioinks suitable for applications involving live cells and tissues.

One of the key challenges in bioprinting is achieving the right balance between structural integrity and cell viability. Physical crosslinking bioinks address this challenge by providing a supportive matrix for the cells while maintaining a favorable environment for their growth and function. This makes them particularly promising for applications such as tissue engineering, where the goal is to create functional tissues or organs for transplantation.

In addition to their biocompatibility, physical crosslinking bioinks offer versatility in terms of material selection. Researchers can choose from a variety of polymers that exhibit the desired physical crosslinking properties. This flexibility allows for customization based on the specific requirements of the target tissue or organ.

In summary, physical crosslinking bioinks represent a vital component in the field of bioprinting. By leveraging non-covalent interactions and responsive materials, these bioinks enable the fabrication of intricate three-dimensional structures with live cells. The reversible nature of physical crosslinks adds a layer of control and biocompatibility, making them a promising avenue for advancing the field of regenerative medicine and tissue engineering. As technology continues to evolve, the development of innovative bioinks and bioprinting techniques holds great potential for revolutionizing healthcare and personalized medicine.


  1. Ashammakhi N, et al.; Bioinks and bioprinting technologies to make heterogeneous and biomimetic tissue constructs. Mater Today Bio. 2019, 1:100008.
For research use only, not intended for any clinical use.