How to Use Host-guest Interaction Crosslinking Bioinks?


The field of 3D bioprinting has revolutionized the way we approach tissue engineering and regenerative medicine. The ability to create intricate three-dimensional structures using bioinks has opened new possibilities for creating functional tissues and organs. One crucial aspect of bioprinting involves the choice of bioinks and their ability to form stable structures. In recent years, the development of host-guest interaction crosslinking bioinks has garnered significant attention for its potential in enhancing the precision and functionality of printed tissues.

The supramolecular hydrogels stabilized by reversible host-guest crosslinks with different binding kinetics possess differential dynamic properties. Figure 1. The supramolecular hydrogels stabilized by reversible host-guest crosslinks with different binding kinetics possess differential dynamic properties. (Yang B, et al.; 2021)

Host-guest interactions involve the binding of molecules based on complementary shapes and charges. In the context of bioprinting, this concept is harnessed to create stable crosslinks between bioink components. The host molecules typically have cavities that can accommodate guest molecules, leading to the formation of robust structures.

Advantages of Host-Guest Interaction Crosslinking Bioinks:

Precision in Printing:

One of the key advantages of using host-guest interaction crosslinking bioinks is the precise control over the printing process. The specific binding between host and guest molecules allows for fine-tuning of the crosslinking density, enabling the creation of intricate structures with high resolution.

Versatility in Material Selection:

Host-guest interaction crosslinking is a versatile approach as it allows for the use of various biomaterials as components of the bioink. This versatility opens up possibilities for creating bioinks tailored to specific tissue types, offering a wide range of applications in tissue engineering.

Enhanced Mechanical Properties:

The host-guest interactions contribute to the mechanical strength and stability of the printed structures. The controlled crosslinking allows for the manipulation of the mechanical properties of the bioink, ensuring that the printed tissues mimic the natural mechanical environment of native tissues.

Biochemical Compatibility:

Host-guest interaction crosslinking bioinks are often designed to be biocompatible, minimizing the potential for adverse reactions when introduced into living organisms. This biochemical compatibility is crucial for successful integration and functionality of the printed tissues within the host environment.

Steps to Use Host-Guest Interaction Crosslinking Bioinks

Selection of Host and Guest Molecules:

The first step in using host-guest interaction crosslinking bioinks is the careful selection of host and guest molecules. This selection is based on the desired properties of the printed tissue and the compatibility of the chosen molecules with the targeted application.

Formulation of Bioink:

Once the host and guest molecules are chosen, the bioink formulation is prepared. This involves combining the selected biomaterials in the appropriate proportions to achieve the desired bioink consistency and rheological properties. The formulation should take into account factors such as viscosity, shear-thinning behavior, and gelation kinetics.

Printing Process:

The bioink is loaded into the 3D bioprinter, and the printing process begins. The precise control over the deposition of bioink allows for the creation of complex, multi-layered structures. The host-guest interactions start to occur during the printing process, leading to the formation of stable crosslinks.

Crosslinking and Maturation:

After the printing process is complete, the printed structure undergoes a crosslinking and maturation phase. This phase allows the host-guest interactions to fully develop, strengthening the structure and ensuring its stability. The maturation period may vary depending on the specific bioink formulation and the targeted tissue type.

Applications of Host-Guest Interaction Crosslinking Bioinks

Organ Transplantation:

The ability to create complex, vascularized structures using host-guest interaction crosslinking bioinks holds great promise for organ transplantation. This approach allows for the precise engineering of organs with intricate architectures, potentially overcoming the shortage of donor organs.

Drug Testing and Development:

Host-guest interaction crosslinking bioinks can be employed to create 3D tissue models for drug testing and development. These models closely mimic the in vivo environment, providing a more accurate representation of how drugs interact with tissues and organs.

Disease Modeling:

Researchers can use host-guest interaction crosslinking bioinks to create 3D tissue models that replicate the characteristics of diseased tissues. This facilitates the study of disease progression and the development of targeted therapies.

Personalized Medicine:

The versatility of host-guest interaction crosslinking bioinks allows for the customization of printed tissues based on individual patient needs. This opens the door to personalized medicine, where tissues and organs can be engineered to match the specific requirements of each patient.

Challenges and Future Directions

While host-guest interaction crosslinking bioinks offer tremendous potential, there are challenges that researchers are actively addressing. These challenges include optimizing bioink formulations for various tissue types, improving printing speed, and enhancing long-term stability.

Future directions in this field involve exploring new host-guest pairs, refining bioink formulations, and advancing printing technologies. Additionally, efforts are underway to integrate other bioactive components, such as growth factors and cells, into host-guest interaction crosslinking bioinks to further enhance tissue functionality.


Host-guest interaction crosslinking bioinks represent a promising avenue in the advancement of 3D bioprinting technology. The ability to precisely control the printing process, tailor bioink formulations, and create functional tissues has the potential to revolutionize medicine and healthcare. As research in this field continues, we can anticipate even more sophisticated and diverse applications, bringing us closer to the realization of complex and functional 3D-printed tissues and organs.


  1. Yang B, et al.; Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics. Nat Commun. 2021, 12(1):3514.
For research use only, not intended for any clinical use.