Page 230 - IJB-9-5

International Journal of Bioprinting Hydrogels for 3D bioprinting

properties, mechanical properties, and other physical and damage cell membranes and cause leakage of intracellular
chemical properties and biological properties, and have a substances [109] . Although some studies have reported the
wide range of applications in the fields of biomedicine and osteogenic ability of GO, its osteogenic mechanism is still
tissue engineering [12,118] . CNTs include single-wall carbon unclear.
nanotubes (SWCNTs) and multi-wall carbon nanotubes Carbon-based nanocomposite hydrogel materials have
(MWCNTs). Sanjuan-Alberte et al. [119] combined the been widely used in biomedical applications, including
conductive properties of MWCNTs with the excellent drug delivery and cellular sensors, due to their unique
biochemical properties of dECM for the first time. The advantages such as excellent optical properties, electrical
results after applying certain electrical stimuli to the scaffold and thermal conductivity, high mechanical strength, and
show that the combination of conductive material with large surface area. However, it has been demonstrated that
external electrical stimuli can drive contractile behavior carbon-based nanocomposite hydrogel materials lead to
similar to physiological conditions. This suggests that this an increased production of reactive oxygen species [125] , and
material has the potential to be used in the future to develop the concentration increases with the higher concentration
smart scaffolds for biosensing/actuation applications. Li of the material. ROS may induce oxidative stress and
et al. [120] used the rotating axis method to print CNT-doped inflammatory responses, which lead to damage to proteins
SA-Gel hydrogel artificial blood vessel stents. They proved and cell membranes, and even affect DNA in the nucleus. In
that the introduction of CNTs enhanced the mechanical addition to the increase in Reactive Oxygen Species (ROS),
properties and deformation recovery ability of SA-Gel the aforementioned CNTs and GO also cause an increase
hydrogel (Figure 5C(iii) and (iv)). Ho et al. [121] studied in autophagosomes in macrophages [126] . The accumulated
the potential of bioprinted poly (ε-caprolactone) (PCL)- autophagosomes will cause cellular autophagy and lysosomal
CNTs composite scaffolds in cardiac tissue engineering. dysfunction, which will further promote ROS synthesis and
Because the incorporation of CNTs increases the degree lead to apoptosis. To mitigate the cytotoxicity of carbon-
of the arrangement of the PCL polymer molecular chains, based nanocomposite hydrogel materials, researchers have
resulting in better crystallinity, the hardness, elastic found that the toxicity is related to their physicochemical
modulus, and maximum peak load of the PCL-CNTs properties, such as particle size, length, and structure [127] .
composite material are all improved. In the cell viability Overall, although carbon-based nanomaterials have many
experiment, by adjusting different concentrations of CNTs, advantages that other materials do not have, they should be
the results showed that the 1 wt% CNT composite material used with care so as to reduce or even avoid cytotoxicity;
has a proliferation effect on H9c2 cardiac cells. Besides, for instance, by modifying the materials or changing
by adjusting the enzyme concentrations, the degradation their physical structure, they can safely be used in tissue
rates can be controlled. CNTs can modify the surface of engineering and regenerative medicine.
the scaffold to enhance the interaction between nerve cells
and biological scaffold materials. The hydrogel mixed with
amine-functionalized MWCNTs and a porous structure 4.3. Nanofiber composite hydrogels
of nerve scaffold was prepared by stereolithography The typical characteristics of nanofiber materials are
printing technology [118] . large surface area to volume ratio and large porosity.
Electrospinning and sol-gel method are commonly
PCL-based polymer materials as scaffolds are widely used used technologies for manufacturing nanofibers.
in tissue engineering. However, the high hydrophobicity Electrospinning is still the most effective technology for
and non-biological activity of the PCL surface will lead manufacturing nanofibers [128,129] . Nanocellulose belongs to
to a decrease in cell affinity and further prevent cells from polysaccharides, the novel type of natural nanomaterials,
attaching to the surface of the scaffolds. Composite with which can be extracted from plant or bacterial
nanomaterials is one of the ways to solve these problems. biosynthesis. It has good biocompatibility, water holding
The nanomaterials could be graphene, CNTs, nanoclays, capacity, stability in a wide range of pH, a nanonetwork
and so on. Although graphene and its derivatives have structure, and high stiffness and strength [130] . We have
many applications in biomedicine, its potential toxicity has been emphasizing the optimization of the hydrogel
gradually been revealed and attracted people’s attention. bioinks formulation. The rheological properties are one
However, the detailed mechanism behind its toxicity has of the fundamental factors in the 3D bioprinting process.
not been fully discovered. It is worth noting that some It is extremely crucial to find a material that can improve
researchers have proposed possible mechanisms [110] . For the printability of the hydrogel and maintain the fidelity
example, the currently widely accepted mechanism of of the shape. This material can also be called a rheology
graphene-induced toxicity is the physical interaction with modifier. In recent years, nanocellulose materials are
cell membranes. The sharp edges of graphene sheets can mainly divided into three categories. The first category is

Volume 9 Issue 5 (2023) 222 https://doi.org/10.18063/ijb.759