Page 375 - IJB-9-1

International Journal of Bioprinting Micro/nano-3D hemostats for rapid wound healing

4.3. Combined techniques scaffold determine overall porosity. Porosity is directly
Current technological advancements have allowed experts proportional to water absorption levels. Therefore, this
in the field of tissue engineering to expand the applicative nanofiber sponge has a higher water absorption percentage
range of various micro/nanostructure-hydrogel constructs than a less porous hemostatic membranous agent.
to a much more comprehensive range of applications. These recent examples show that the field of tissue
This rapid expansion in applications has mainly been engineering has significantly benefited from the combined
possible due to the breakthrough discovery involving the use of 3D printing with electrospinning techniques. These
design of stimuli-responsive nanocomposite hydrogels, combined technologies have allowed the fabrication of
which biomimetically respond to internal and external highly tunable hemostatic agents such as scaffolds inlaid
biophysical and biochemical stimuli from the macroscopic with composite micro/nanostructures. Depending on
to the nanoscopic scale [106] . Thus, additive manufacturing the choice of fabrication techniques and materials, these
and electrospinning techniques are currently the potent agents can be fabricated with nanoscopic precision in
and practical tools for tissue engineering applications, their architecture, thus affecting their biophysical and
especially in manufacturing micro/nanostructures for mechanical properties [12,66] . Customized modules can also
rapid hemostasis. However, when combined, additive be fabricated in a patient-specific manner, thus helping
manufacturing and electrospinning techniques allow for to accelerate the natural wound healing and regenerative
[7]
the possibility and the ease of selecting different types of process on a case-by-case basis.
materials to enable the fabrication of specifically designed
complex multiscale structures with multiple mesh layers Every fabrication technique has advantages and
and fiber densities (Figure 6A). limitations, so we must consider these aspects and
appropriately select materials when designing micro/
The material–cell biointerface is a significant aspect
in combined micro/nanosurface modification methods nanostructures for rapid hemostasis. Aside from 3D/4D
printing, we can combine other additive manufacturing
for hemostat fabrication. This is because the mechanical techniques with electrospinning to create micro/
interactions between a cell and its surrounding nanostructures with highly tunable characteristics.
biochemical and biophysical environment influence cell These techniques include extrusion methods [108,109] ,
behavior and function. When combining 3D printing stereolithography (SLA) [110] , and digital light processing
with electrospinning, modifications are possible due to (DLP) [56,111] . These fabrication methods are not as prevalent
the choice of material in fabrication, solution viscosity, as inkjet 3D printing because most of them require the
and internal mechanochemical interactions. Different addition of processing additives, such as photoactive
3D-printed substrates, such as steel, plastic, and glass, resins, which are not biocompatible and may damage
demonstrate varying levels of shear strength concerning the body. Furthermore, some fabrication techniques are
displacement when a force is applied, impacting cellular incompatible with standard and valuable hemostatic
kinetics. We can see mechanical-induced deformation due materials. However, regardless of these drawbacks,
to the stretching and relaxation of an alginate hydrogel extrusion methods, SLA, and DLP offer the advantage of
on the 3D-printed scaffold shown in Figure 6B. Such high-resolution printing of features on the nanoscale level,
electrospun fiber mats can also be inlaid with cells or along with other fabrication-specific benefits.
particles before incorporation into the 3D-printed scaffold
to tune the desired effect of the resultant hemostat. This Extrusion-based printing methods use pneumatic air
further enhances a fabricated agent’s hemostatic capacities pressure or mechanical forces, which are generated using
by preventing blood loss and reducing hemostasis pistons or screws, respectively, to carve out user-defined 3D
time [88,107] . As shown in Figure 6C, an electrospun nanofiber patterns from bio-inks. These printing methods fabricate
mat is combined with a 3D-printed scaffold to create a 3D chitosan-based bio-inks for 3D scaffold construction [105] .
[94]
nanofibrous scaffold for rapid hemostasis . Gallium-based inks also influence blood clotting, enhance
thrombin generation, and induce antibacterial activity [112] .
Other examples showing the beneficial results of
combined fabrication include developing electrospun Extrusion methods have been used for developing novel
gallium-containing chitosan-based composite scaffolds as
multiwall carbon nanotubes grafted to a 3D-printed hemostatic agents [113] .
oxidized regenerated cellulose gauze. Hemostatic evaluation
of a similar electrospun sponge can be seen in Figure 6D. SLA is a laser-based printing technique that uses laser
Meanwhile, Figure 6E demonstrates how the morphology pulses to produce high-resolution, high-viscosity droplets
of a gelatin nanofiber sponge can be quickly restored after on the printing surface [114] . Though the operating speed of
undergoing different degrees of compression . The density SLA is slower compared to other printing methods, cells
[7]
and diameter of electrospun fibers on this 3D-printed printed via this method experience less mechanical stress

Volume 9 Issue 1 (2023)olume 9 Issue 1 (2023)
V 367 https://doi.org/10.18063/ijb.v9i1.648