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3D Printing of hydrogel composite systems: Recent advances in technology for tissue engineering

ionic crosslinking. The perfusable structures with multiple composites induced cell toxicity.
layers and various diameters were formed by coaxial 4.4 4D printing
nozzle systems in a one-step process. The rheological and
mechanical properties of the printed hydrogel composites The applications of the hydrogel composite systems
were tunable by PEGTA and endothelial and mesenchymal are not only limited to mechanical strengthening or
stem cells incorporated hydrogel composites also showed biological performance. They are also valuable model
favorable biological responses which demonstrated the systems for stimuli-responsive smart materials, also
formation of vessels resembling early maturation of the known as 4D printing. 4D printing involves materials
native vasculature. that are responsive to external stimuli such as electricity,
PEG derivatives were used as crosslinkers to develop light, ions, temperature, and water, such that the pre-
bioartificial vessel-like grafts. Different four-armed printed 3D configuration changes over time [92,134–138] .
polyethylene glycol(PEG) derivatives called TetraPEG8 and In general, shape memory polymers (SMPs) are popularly
TetraPEG13 were converted to tetra-acrylate derivatives used for the 4D printing which have permanent shape by
(TetraPAcs) and these were co-crosslinked with hyaluronan a cross-linked polymer network, and can be deformed into
acid and gelatin hydrogels into synthetic extracellular matrices a temporary shape via reversible interactions between the
(sECMs) by Skardal et al. (Figure 11C) [132] . The crosslinked networks. When exposed to external stimuli, the material
hydrogel composites showed improved rheological properties can recover its original shape. However, most SMPs only
which are more suitable for bioprinting when compared possess 3D printability with laser-based printing systems
with sECM hydrogels crosslinked with PEGDA. Bioprinted such as Polyjet or SLA 3D printing [135,136] . Therefore, there
hydrogel composites containing NIH3T3, HepG2 C3A, and are severe limitations on the choice of material and function
Int407cells exhibited microcapillary tube structure with cells for tissue engineering applications.
viability up to 4 weeks. In the case of hydrogel composite, they have a great
Dolati proposed bioprintable vascular conduits reinforced potential as a platform technology to extend material choice
by carbon nanotubes [133] . Multiwalled carbon nanotubes for 4D printing with their highly tunable functionalities.
(MWCNTs) were dispersed in alginate hydrogels and For example, it is possible to utilize hydrogel composites
human coronary artery smooth muscle cells (HCASMCs) for water-activated 4D printing. In general, reinforcements
encapsulated hydrogel composites were extruded by coaxial such as inorganic particles or fillers do not or exhibit less
nozzle. As contents of MWCNTs increased, the mechanical swelling behavior in water as compared to hydrogels (Figure
properties of hydrogel composites increased. However, in 12A). The orientation or distribution of reinforcements
long-term biological responses, MWCNT-added hydrogel within the hydrogel composite generates controllable

Figure 11. Various strategies of constructing vascular system (A) using a multiple coaxial nozzle with alginate, GelMA, and 4-arm
PEGTA (reproduced with permission from [131]. Copyright 2016, Elsevier Ltd), (B) bioprinting layer-by-layer with collagen, fibrin-cell
mixture, and sacrificial gelatin, (reproduced with permission from [140]. Copyright 2017, Springer International Publishing AG.) and (C)
by stacking hydrogel macrofilaments to form a cellularized tubular structure(reproduced with permission from [132]. Copyright 2010,
Elsevier Ltd).

20 International Journal of Bioprinting (2018)–Volume 4, Issue 1