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RESEARCH ARTICLE

A dual crosslinking strategy to tailor rheological

properties of gelatin methacryloyl

1†
2†
Miaomiao Zhou , Bae Hoon Lee and Lay Poh Tan 1,3*
1 School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798,
Singapore
2 Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou 325011, China
3 Singapore Centre for 3D Printing (SC3DP), Singapore 639798, Singapore

Abstract: 3D bioprinting is an emerging technology that enables the fabrication of three-dimensional organised cellular
constructs. One of the major challenges in 3D bioprinting is to develop a material to meet the harsh requirements (cell-
compatibility, printability, structural stability post-printing and bio-functionality to regulate cell behaviours) suitable for
printing. Gelatin methacryloyl (GelMA) has recently emerged as an attractive biomaterial in tissue engineering because it
satisfies the requirements of bio-functionality and mechanical tunability. However, poor rheological property such as low
viscosity at body temperature inhibits its application in 3D bioprinting. In this work, an enzymatic crosslinking method
2+
triggered by Ca -independent microbial transglutaminase (MTGase) was introduced to catalyse isopeptide bonds formation
between chains of GelMA, which could improve its rheological behaviours, specifically its viscosity. By combining en-
zymatic crosslinking and photo crosslinking, it is possible to tune the solution viscosity and quickly stabilize the gelatin
macromolecules at the same time. The results showed that the enzymatic crosslinking can increase the solution viscosity.
Subsequent photo crosslinking could aid in fast stabilization of the structure and make handling easy.
Keywords: microbial transglutaminase; enzymatic crosslinking; photo crosslinking; viscosity

*Correspondence to: Lay Poh Tan, School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue,
Singapore 639798, Singapore; Email: LPTan@ntu.edu.sg
† These authors contributed equally to this paper.

Received: April 19, 2017; Accepted: June 7, 2017; Published Online: June 11, 2017
Citation: Zhou M, Lee B H and Tan L P, 2017, A dual crosslinking strategy to tailor rheological properties of gelatin methacryloyl.
International Journal of Bioprinting, vol.3(2): 130–137. http://dx.doi.org/10.18063/IJB.2017.02.003.

1. Introduction 3D constructs layer by layer, in which cells mixed with
[4]
[1]
rgan shortage calls for a great need for the biomaterials can be distributed in a certain position .
development of new biological substitutes. This direct method makes it an attractive tool for the
OTissue engineering has emerged as an attract- development of 3D-organised cellular constructs with
[5]
ive method to meet this need. The classic tissue eng- special biological and mechanical properties .
ineering strategy is to seed specific cells isolated One major challenge of 3D bioprinting is to develop a
from a biopsy onto a three-dimensional (3D) scaffold, printing material to meet a repertoire of characteristics
occasionally incorporating growth factors, to provide a suit able for printing. The printing materials should
temporal support for cell proliferation, differentiation have suitable physiochemical properties such as shear
[2]
and eventually formation of neotissue . One major thinning, high viscosity, as well as post-printing struc-
limitation of this strategy is the lack of precision in cell tural stability [6,7] . Moreover, the materials should
placement due to manual cell seeding; it is difficult to provide a desirable environment for cells to encapsulate,
[8]
place different cell types at certain position depending migrate, proliferate and differentiate . Hydrogels
[3]
on the type and function of a tissue . To overcome this exert great potential as printing materials due to their
drawback, an automated and precise technology known cell-encapsulating ability and their mimicking of
as 3D bioprinting has gained scientists’ interest in recent physical and chemical properties of the extracellular
[9]
years. It is a computer-controlled process to produce matrix (ECM) . The difficulty lies in the delicate ba-
A dual crosslinking strategy to tailor rheological properties of gelatin methacryloyl. © 2017 Miaomiao Zhou, et al. This is an Open Access article
distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-
nc/4.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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