Using GelMA for 3D Bioprinting

Gelatin Methacrylate (GelMA) hydrogels are developed to offer an optimal combination of biochemical and biomechanical properties. They are commonly used as bioinks for bioprinting 3D constructs due to their biocompatibility, functionality, and physicochemical properties, which provide a favorable environment for cellular activities, such as proliferation, spreading migration, and differentiation. Cell-laden GelMA bioprinted constructs present high structural fidelity after deposition and have already been used successfully in vascular, cartilage, skeletal muscle, and cardiac tissue engineering [1,2].

Figure 1: 3D bioprinting of bioinks composed of cells and GelMA [1].

In the production process of GelMA, the gelatin is first derivatized by reaction with methacrylic anhydride, to be crosslinked in a subsequent step. After a number of suitable polymerization processes, including redox, UV treatment, γ-irradiation, and electronic beam curing, the water-soluble gelatin obtained after derivatization can be crosslinked. Crosslinking by UV irradiation is performed in the presence of water-soluble photoinitiators [3].

The chemical structuring of the final gel is controlled by the degree of substitution (or functionalization) of the gelatin and its concentration [3]. It has been demonstrated that GelMA hydrogels with low concentrations are more suitable cell-laden bioinks attributable to their high cell stability and viability. In contrast, GelMA bioinks with high concentrations have excellent printability. These factors endorse the use of GelMA for 3D bioprinting strategies as an essential tool for treating tissue injuries [4,5].

Recent investigations have shown that GelMA hydrogels are promising bioinks to build constructs with various 3D architectures due to their close resemblance to some essential properties of the extracellular matrix and their potential to form covalently crosslinked hydrogels under UV light exposure [5,6]. A research analyzed the effects of GelMA concentration, extruder pressure, and duration of UV exposure on cardiac myocytes and fibroblasts’ survival. The first step was to evaluate how the rate of GelMA extrusion and the fidelity of printed struts were affected by temperature and pressure settings. Cell survival rate on 3D printed cardiomyocyte-laden GelMA constructs was more sensitive to extruder pressure and GelMA concentrations than it was on fibroblast-laden GelMA constructs. Both types of constructs were adversely impacted by the UV curing step. Using mixed cell populations and enriching bioink formulation improved cell survival and proliferation [7].

Figure 2: Dual extruder printing using cardiac myocyte- and cardiac fibroblast-laden GelMA [7].

The MatriXpec™ GelMA hydrogels by TissueLabs are a combination of GelMA with the traditional MatriXpec™, developed to allow UV photocrosslinking and offer an optimal association of biochemical and biomechanical properties for bioprinting 3D constructs based on tissue-specific microenvironments. This formulation can be used as an additional strategy to improve cell survival and network formation within 3D printed GelMA constructs.

REFERENCES

1- Ashammakhi, N.; Ahadian, S.; Xu, C.; Montazerian, H.; Ko, H.; Nasiri, R.; Barros, N.; Khademhosseini, A. (2019). Bioinks and Bioprinting Technologies to Make Heterogeneous and Biomimetic Tissue Constructs. Materials Today Bio 1, 100008.

2- Asghari Adib, A.; Sheikhi, A.; Shahhosseini, M.; Simeunović, A.; Wu, S., Castro, C.E.; Zhao, R.; Khademhosseini, A.; Hoelzle, D.J. (2020). Direct-write 3D printing and characterization of a GelMA-based biomaterial for intracorporeal tissue engineering. Biofabrication 12, 045006.

3- Van Den Bulcke, A.I.; Bogdanov, B.; De Rooze, N.; Schacht, E.H.; Cornelissen, M.; Berghmans, H. (2000). Structural and Rheological Properties of Methacrylamide Modified Gelatin Hydrogels. Biomacromolecules 1, 31-38.

4- Xiao, S.; Zhao, T.; Wang, J.; et al. (2019). Gelatin Methacrylate (GelMA)-Based Hydrogels for Cell Transplantation: an Effective Strategy for Tissue Engineering. Stem Cell Reviews and Reports 15(5), 664-679.

5- Yue, K.; Trujillo-de-Santiago, G.; Alvarez, M.M.; Tamayol, A.; Annabi, N.; Khademhosseini, A. (2015). Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials 73, 254-271.

6- Yin, J.; Yan, M.; Wang, Y.; Fu, J.; Suo, H. (2018). 3D Bioprinting of Low-Concentration Cell-Laden Gelatin Methacrylate (GelMA) Bioinks with a Two-Step Cross-linking Strategy. ACS Applied Materials & Interfaces 10, 6849-6857.

7- Koti, P.; Muselimyan, N.; Mirdamadi, E.; Asfour, H.; Sarvazyan, N.A. (2019) Use of GelMA for 3D printing of cardiac myocytes and fibroblasts. Journal of 3D Printing in Medicine 3(1):11-22.