What Materials are Suitable for Printing with Photo-crosslinked Bioinks?


In the realm of modern bioprinting, the development of bioinks has revolutionized tissue engineering and regenerative medicine. These bioinks serve as the "ink" in 3D bioprinters, enabling the precise deposition of living cells to fabricate intricate tissue structures layer by layer. One promising advancement in this field is the utilization of photo-crosslinking techniques to solidify bioinks into stable structures. Photo-crosslinked bioinks offer advantages such as improved printability, enhanced structural integrity, and tunable mechanical properties. However, the selection of suitable materials for printing with photo-crosslinked bioinks is crucial for achieving desired biological and mechanical outcomes. In this article, we delve into the characteristics and considerations of materials compatible with photo-crosslinked bioinks in bioprinting applications.

Schematic illustration of photo-crosslinkable hydrogels for the bioprinting of bone and cartilage.Figure 1. Schematic illustration of photo-crosslinkable hydrogels for the bioprinting of bone and cartilage.(Tan G, et al.; 2022)

Characteristics of Suitable Materials

  • Biocompatibility:

The foremost requirement for materials compatible with photo-crosslinked bioinks is biocompatibility. These materials must not induce cytotoxicity or adverse immune responses when in contact with living cells. Biocompatible materials ensure cell viability and functionality, facilitating the development of viable tissue constructs.

  • Photo-reactivity:

Materials used in photo-crosslinked bioinks should exhibit photo-reactivity, meaning they can undergo crosslinking upon exposure to specific wavelengths of light. Photoinitiators are often incorporated into bioinks to initiate the crosslinking process, making it essential for materials to efficiently interact with these initiators and undergo crosslinking under controlled conditions.

  • Mechanical Properties:

The mechanical properties of printed constructs play a crucial role in mimicking the native tissue environment and supporting cell growth and tissue maturation. Suitable materials should offer tunable mechanical properties that can be adjusted to match those of the target tissue. This includes considerations such as stiffness, elasticity, and tensile strength.

  • Printability:

Printability refers to the ability of materials to flow smoothly through the printing nozzle and form precise structures during the bioprinting process. Materials must possess appropriate rheological properties, such as viscosity and shear-thinning behavior, to enable accurate deposition and layer-by-layer assembly without compromising structural integrity.

  • Biodegradability:

In many tissue engineering applications, it is desirable for printed constructs to degrade over time as they integrate with surrounding tissues and facilitate tissue regeneration. Biodegradable materials are preferred for this purpose, as they can be gradually replaced by newly formed tissue while maintaining structural support during the healing process.

  • Biofunctionality:

Materials compatible with photo-crosslinked bioinks may also offer inherent biofunctionality, meaning they can mimic specific biochemical and biomechanical cues present in the native tissue microenvironment. Incorporating bioactive molecules, such as growth factors or cell adhesion peptides, into these materials can further enhance cellular responses and tissue regeneration.

Materials Suitable for Printing with Photo-crosslinked Bioinks:

  • Gelatin Methacryloyl (GelMA):

GelMA is a derivative of gelatin modified with methacryloyl groups, enabling photo-crosslinking upon exposure to ultraviolet (UV) light in the presence of a photoinitiator. GelMA possesses excellent biocompatibility due to its origin from natural collagen and offers tunable mechanical properties by adjusting the degree of methacrylation. Its printability and ability to support cell adhesion and proliferation make it a popular choice for bioprinting applications.

  • Hyaluronic Acid (HA) Methacrylate:

Hyaluronic acid, a naturally occurring polysaccharide in the extracellular matrix, can be modified with methacrylate groups to form HA methacrylate. This modified HA retains its bioactivity while enabling photo-crosslinking for bioprinting purposes. HA methacrylate-based bioinks exhibit excellent biocompatibility and biofunctionality, promoting cell migration and tissue regeneration, particularly in cartilage and wound healing applications.

  • Polyethylene Glycol (PEG) Diacrylate:

Polyethylene glycol diacrylate is a synthetic polymer that undergoes rapid and efficient photo-crosslinking upon exposure to UV light. PEG-based hydrogels offer customizable mechanical properties and degradation rates, making them suitable for a wide range of tissue engineering applications. Additionally, PEG diacrylate bioinks can be functionalized with cell-adhesive peptides or growth factors to modulate cellular behavior and tissue development.

  • Methacrylated Alginate:

Alginate, derived from seaweed, can be modified with methacrylate groups to form methacrylated alginate, which undergoes crosslinking under UV light exposure. Methacrylated alginate combines the biocompatibility of alginate with the photo-reactivity of methacrylate groups, allowing for precise control over gelation kinetics and mechanical properties. This bioink has been utilized in various bioprinting applications, including vascular tissue engineering and wound healing.

  • Fibrinogen-Based Bioinks:

Fibrinogen, a key component of the blood clotting cascade, can be employed as a bioink for bioprinting applications. Upon mixing with thrombin and calcium ions, fibrinogen undergoes rapid polymerization to form a fibrin hydrogel, which can be further crosslinked using UV light in the presence of photoinitiators. Fibrin-based bioinks closely mimic the native extracellular matrix environment and support cell encapsulation and proliferation, making them suitable for tissue regeneration and organoid fabrication.

Challenges and Future Directions

While materials suitable for printing with photo-crosslinked bioinks offer immense potential in tissue engineering and regenerative medicine, several challenges remain to be addressed. One significant challenge is achieving precise control over material properties, including mechanical strength, degradation kinetics, and bioactivity, to meet the specific requirements of diverse tissue types. Additionally, optimizing printing parameters, such as light intensity, exposure time, and spatial resolution, is crucial for fabricating complex tissue constructs with high fidelity and structural integrity.

Future research directions in this field may focus on the development of novel bioink formulations that integrate multiple materials or incorporate bioactive molecules to enhance cellular responses and tissue regeneration. Advanced fabrication techniques, such as multi-material bioprinting and bioprinting at the microscale, hold promise for creating biomimetic tissue constructs with intricate architectures and functional properties. Furthermore, efforts to translate bioprinted tissues from bench to bedside necessitate thorough preclinical testing and regulatory approval processes to ensure safety and efficacy in clinical applications.


The selection of suitable materials is paramount for successful bioprinting with photo-crosslinked bioinks, as these materials dictate the biological and mechanical properties of printed constructs. Biocompatible, photo-reactive materials with tunable mechanical properties, printability, biodegradability, and biofunctionality are essential for fabricating functional tissue constructs for various applications in regenerative medicine and beyond. By overcoming existing challenges and exploring innovative material formulations and printing strategies, the field of bioprinting holds immense promise for revolutionizing healthcare and addressing unmet clinical needs in tissue replacement and regeneration.

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  1. Tan G, et al.; Photo-Crosslinkable Hydrogels for 3D Bioprinting in the Repair of Osteochondral Defects: A Review of Present Applications and Future Perspectives. Micromachines (Basel). 2022, 13(7):1038.
For research use only, not intended for any clinical use.