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ORIGINAL ARTICLE

3D Freeform Printing of Nanocomposite Hydrogels

through in situ Precipitation in Reactive Viscous Fluid

Shengyang Chen , Tae-Sik Jang , Houwen Matthew Pan , Hyun-Do Jung , Ming Wei Sia ,
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2
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Shuying Xie , Yao Hang , Seow Khoon Mark Chong , Dongan Wang , Juha Song *
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1 School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, 637457, Singapore
2 Liquid Processing and Casting Technology R&D Group, Korea Institute of Industrial Technology, Incheon 406-840, Republic
of Korea
3 School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225009, Jiangsu, P. R. China
4 Department of Biomedical Engineering, City University of Hong Kong,83 Tat Chee Avenue, Kowloon Tong, Hong Kong
Abstract: Composite hydrogels have gained great attention as three-dimensional (3D) printing biomaterials because of their
enhanced intrinsic mechanical strength and bioactivity compared to pure hydrogels. In most conventional printing methods for
composite hydrogels, particles are preloaded in ink before printing, which often reduces the printability of composite ink with
little mechanical improvement due to poor particle-hydrogel interaction of physical mixing. In contrast, the in situ incorporation
of nanoparticles into a hydrogel during 3D printing achieves uniform distribution of particles with remarkable mechanical
reinforcement, while precursors dissolved in inks do not influence the printing process. Herein, we introduced a “printing
in liquid” technique coupled with a hybridization process, which allows 3D freeform printing of nanoparticle-reinforced
composite hydrogels. A viscoplastic matrix for this printing system provides not only support for printed hydrogel filaments
but also chemical reactants to induce various reactions in printed objects for in situ modification. Nanocomposite hydrogel
scaffolds were successfully fabricated through this 3D freeform printing of hyaluronic acid (HAc)-alginate (Alg) hydrogel inks
through a two-step crosslinking strategy. The first ionic crosslinking of Alg provided structural stability during printing, while
the secondary crosslinking of photo-curable HAc improved the mechanical and physiological stability of the nanocomposite
hydrogels. For in situ precipitation during 3D printing, phosphate ions were dissolved in the hydrogel ink and calcium ions were
added to the viscoplastic matrix. The composite hydrogels demonstrated a significant improvement in mechanical strength,
biostability, as well as biological performance compared to pure HAc. Moreover, the multi-material printing of composites with
different calcium phosphate contents was achieved by adjusting the ionic concentration of inks. Our method greatly accelerates
the 3D printing of various functional or hybridized materials with complex geometries through the design and modification of
printing materials coupled with in situ post-printing functionalization and hybridization in reactive viscoplastic matrices.
Keywords: Three-dimensional freeform printing, in situ precipitation, Hydrogels, Nanocomposites, Viscous fluid matrix,
Multi-materials

*Corresponding Author: Juha Song, School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive,
637457, Singapore; songjuha@ntu.edu.sg

Received: January 28, 2020; Accepted: March 03, 2020; Published Online: April 02, 2020
Citation: Chen S, Jang TS, Pan HM, et al., 2020, 3D Freeform Printing of Nanocomposite Hydrogels through in situ
Precipitation in Reactive Viscous Fluid., Int J Bioprint, 6(2):258. DOI: 10.18063/ijb.v6i2.258.

1 Introduction the ability to fabricate structurally, functionally,

Recent advances in three dimensional (3D) and compositionally intricate constructs [1-4] .
printing technologies have facilitated the Particularly, composite hydrogels have gained
development of composite biomaterials through a great attention as 3D printing biomaterials

© 2020 Chen, 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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