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

increased antibacterial activity . Platelets adhesion to Due to inherent fabrication properties, such as incurred
[89]
nanofibers also becomes possible, as does fiber weight stress and adhesion levels, the hemostatic agents may
loss due to changes in pH throughout the wound healing induce different hemostasis mechanisms. Such mechanisms
process. Such CNF-enabled wound dressings show proceed either by mechanical promotion, augmentation of
promise for synergistic therapy involving NIR-responsivity the blood clotting cascade, binding tissues or blood vessels
via photodynamic chemotherapy for hemostasis and via adhesion kinetics, or preventing leakage from blood
subsequent wound healing. Aside from conductivity, vessels . However, all resultant 3D-printed hemostatic
[66]
these wound dressings feature the beneficial properties agents feature properties beneficial to rapid hemostasis,
of biocompatibility and shape adaptability, all of which such as porosity, immunomodulation, and a pro-coagulant
allow for the maintenance of a bioactive and controllable effect based on material selection [77,97] .
microenvironment [49,90] .
Cryogenic 3D-printed hydrogel scaffolds are one type
For example, in Figure 4B, blood loss is evaluated of hemostatic agent currently manufactured for rapid
for the prepared nonwetting CNF–kaolin composite hemostasis and subsequent diabetic and chronic wound
nanostructured wound dressing measured at 5 minutes healing support. Other hemostats include porous Ga-
compared to the CNF gauze from a reference study . This MBG/CHT composite scaffolds of various sizes fabricated
[83]
study used the commercial fast clotting gauzes (Celox and via the interaction of NH and OH groups of CHT with
2
QuickClot) and the standard gauze (control). silanol groups of Ga-MBG.
Other studies [74,91] have revealed that fiber weight 3D printing of hemostatic agents allows the resulting
affects a hemostat’s time to achieve hemostasis (Figure 4C). construct to undergo a series of macroscopic compression
Similar studies have shown that fiber diameter affects and expansion, with little to no incurred damage. The
resultant mechanical properties such as Young’s modulus, sponge’s original morphology can be quickly restored after
stress, strain, and toughness (Figure 4D). Through this being subject to varying degrees of compression . Similarly,
[98]
tunability and other features, such as low density and several studies demonstrate the compression stress–strain
high porosity, multifunctional electrospun aerogel fibers curves of freeze-dried 3D-printed honeycomb structures
have attracted much attention lately as a novel platform with cellulose concentrations of 4, 5, and 6 wt% .
[99]
for hemostat design [92-94] . Along with excellent mechanical
properties and increased surface area, conscientious By incorporating micro/nanostructures, such as
material selection allows aerogel fibers the properties of micro/nanoparticles, into the fabricated scaffold dressing,
superhydrophobicity and excellent thermal insulation promoting hemostasis in these hydrogels becomes possible
performance, thus allowing them to be ideal candidates for through the release of bioactive exosomes and the sustained
hemostat development . proliferation and migration of cells [100] . 3D printing also
[95]
affects the blood clotting kinetics of composite scaffolds, as
4.2. 3D printing shown in Figure 5B.
Even though we highly value electrospinning techniques Another hemostatic agent developed using 3D printing
for manufacturing effective hemostatic agents, it is not technologies is scaffolds combined with hybrid hydrogels
the only technique applied in hemostat design. Additive laden with microparticles of chitosan methacrylate
manufacturing techniques, such as 3D printing, have (CHMA) and polyvinyl alcohol (PVA). This material
favorable results in fabricating various hemostatic agents, combination allows for the fabricated scaffold’s mechanical
particularly those incorporating micro/nanostructures properties tunability, thus imbuing the resulting agent
into their design. These hemostatic agents promote with the most optimal viscoelasticity and shear thinning
hemostasis and support wound healing utilizing topically characteristics for spatiotemporal manipulation to ensure
administered methods, intracavitary, or intravenous rapid hemostasis. A CHMA–PVA mixture also supports the
applications. Popular 3D-printed hemostatic agents include growth of cells. It provides the inlaid microparticles with
gels, adhesives, sealants, patches, sponges, scaffolds, and the necessary responsivity to differentiate these cells via
foam-creation products. We favor porous agents, such as the spatiotemporal translation of chemical, physical, and
scaffolds and hydrogels, because of their ability to disrupt bioactive cues throughout the wound healing process [101] .
scar formation via their architecture [85,96] . Chitosan–PLA
composites are highly favored materials for 3D printing Using biodegradable 3D-printed polyurethane
because of their ease in printing micro/nanosurfaces hydrogel–scaffold composites (G-DLPU3) also helps
(Figure 5A). Fabricated hemostatic agents can facilitate induce hemostasis and reduce the wounded area over
cell attachment, promoting tissue regeneration through time [102] . Adhesion kinetics of hemostatic glues, such
printed micro/nanostructures and surface patterning. as cyanoacrylate (CA) and other rigid adhesives (TA),

Volume 9 Issue 1 (2023)olume 9 Issue 1 (2023)
V 365 https://doi.org/10.18063/ijb.v9i1.648