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3D freeform printing of nanocomposite hydrogels
because of their materiality, micro- and macro- hydrogels with a relatively slow solidification
structures and functions are comparable to rate [15-19] . Compared with conventional 3D printing
those of biological tissues, with their enhanced in air, embedded freeform 3D printing requires
intrinsic mechanical strength and bioactivity the two shear thinning materials to have matching
compared to pure hydrogel systems [5-8] Among properties, particularly their shear moduli and
various hydrogel systems, hyaluronic acid (HAc)- shear thinning yield stresses [19,20] . How material
based composite hydrogels have been applied parameters influence printability and print quality
for tissue scaffolds due to non-immunogenic, has been extensively studied [15,20] . Shear thinning of
biocompatible, and enzymatically biodegradable viscous matrices has been achieved by fabricating
natures of HAc [9-11] . By incorporating calcium polymer–nanoparticle composites or dispersing
phosphate (CaP), HAc composites exhibited the hydrogel particles in water [15,17,19,20] . Moreover,
significantly improved mechanical, biochemical, in addition to the mechanical support provided by
and biological properties, which could be used the printed soft filaments, a crosslinking agent that
for dermal fillers or spacers [6,12,13] . Most inorganic- induces the solidification of the printed material is
hydrogel composites are printed using composite often included in the matrix. Alginate (Alg) or silk
inks consisting of inorganic particles dispersed in a fibroin-based inks have been successfully printed
hydrogel-forming ink before 3D printing [6,7] . This and crosslinked within hydrogel-based beds for
simple mixing approach to prepare composites biomedical applications [17,19] . One of the greatest
not only allows easy control over the loading advantages of printing in the liquid is the unique
of inorganic particles but is also cell-friendly to flexibility of the chemical environment. However,
enable bioprinting with cells. However, optimizing despite the revolutionary achievements in freeform
the printability of the composite inks and print printing, viscous fluid matrices have not been
quality often becomes more challenging with used for the functionalization or hybridization of
increased particle loading. The previous studies printed materials.
have demonstrated that composite inks with only Here, we present a hybridization process
up to 10% nanoparticle loading show suitable for a 3D freeform printing system to fabricate
printability and structural accuracy. Moreover, composite hydrogel scaffolds in conjunction with
the mechanical properties of composite hydrogels in situ precipitation of a mineral phase. By varying
depend on the particle-hydrogel interactions and the concentration of CaP in a HAc-Alg hydrogel,
often require an additional modification of either we developed HAc-Alg/CaP nanocomposite
the particles or hydrogels for enhancement of scaffolds with a two-step crosslinking strategy,
mechanical properties . including physical crosslinking of Alg and
[6]
To overcome these limitations, in situ photo-crosslinking of glycidyl methacrylate
incorporation of nanoparticles has been proposed, HAc (GM-HAc). To review the effectiveness
whereby permeated ions within the hydrogel of our method, we compared the structural
structures are reacted by drastically increasing compositions, mechanical, physiological, and
the pH, and nanocrystals are nucleated on the biological properties between our printed HAc-
functional groups of the polymer chains within CaP nanocomposite scaffolds and pure hydrogels
the hydrogels. This in situ precipitation method or composite hydrogels generated through ex situ
achieves uniform distribution of the nanoparticles, CaP incorporation. Furthermore, by varying the
strong particle–polymer bonding, and remarkable concentrations of calcium or phosphate ions,
mechanical reinforcement in the hydrogel [5,13,14] . multi-material printing of HAc-Alg/CaP with the
One of the possible printing methods to enable differing extent of mineralization was achieved
in situ precipitation-coupled 3D printing is with high precision. Taken together, we envisage
freeform printing in viscous fluid matrices. that our method can accelerate 3D printing
Freeform 3D printing allows an omnidirectional using various functional or hybridized materials
printing path using mechanically unstable with complex geometries through the design

30 International Journal of Bioprinting (2020)–Volume 6, Issue 2