Page 377 - IJB-9-1

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

printing functional living skin. This method effectively could rapidly swell by 16 times upon blood absorption.
incorporates living cells into hydrogel-based bio-inks to The application of the cryogel was closely associated with
create topical wound dressings with excellent hemostatic the activation of the endogenous coagulation system,
potential and mechanical strength. This fabrication leading to hemostasis within 2 minutes of application [123] .
approach supports cell proliferation, migration, and Huang et al. reported the fabrication of numerous high-
subsequent skin regeneration by forming a suitable strength composite cryogel hemostats comprising PVA,
microenvironment mediated by air, moisture, and carboxymethyl chitosan (CMCS), and dopamine (DA)
nutrient exchange [118] . Additionally, when combined with (PVA/CMCS-DA). The variation in the concentration of
DLP printing, electrospun nanofiber-based scaffolds can the DA resulted in dramatic changes in the hemostatic
provide cells with 3D microenvironments and biomimetic ability of the prepared cryogel. The cryogel incorporated
fibrous structures that promote tissue regeneration, thus with 6 mg of DA exhibited favorable hemostatic ability by
enhancing the structural and bioactive effects of the promoting the adhesion and activation of blood cells [124] .
resultant 3D-printed scaffold . Teng et al. used the ice templating method to fabricate shape-
[14]
Soft lithography is another fabrication technique recoverable gelatin/laponite nanoclay-based macroporous
utilized with other fabrication methods and additive hydrogel hemostat. The fabricated macroporous hydrogel
manufacturing [119,120] . Soft lithography techniques can showed precise clotting ability as a noncompressible
be utilized to create highly biomimetic, precise, and hemostat on liver bleeding. The rapid hemostasis is
complex micro/nanostructures using popular hemostatic attained by the ability of the hydrogel to absorb blood,
materials . Thus, soft lithography methods are primarily subsequently concentrating the coagulation factors. The
[47]
employed in fabricating organ-on-a-chip platforms for drug incorporation of laponite nanoclay enables the activation
development and personalized medicine applications of the endogenic coagulation cascade and accelerates
[44]
rather than hemostats adapted for clinical use [121] . thrombus formation. The prepared macroporous hydrogel
displayed high affinity for blood cell in an irregular
5. Hydrogels and cryogels as hemostats fashion. The irregular aggregation of the blood cells was
linked to the interconnected porous structure with a high
Cryogels microspheres are one of the promising smart volume expansion ratio. The affinity of the hydrogel for
hemostatic materials that can deal with noncompressible the blood cells has primarily resulted from the anisotropic
bleeding within seconds. Such cryogels are reported to charge distribution of the nanoclay. The anisotropic charge
absorb blood within seconds. Zhan et al. reported the distribution greatly enhances concentrating clotting factor,
fabrication of cellulose@polydopamine/Thymol (Tm/ ultimately shortening blood coagulation time [125] . An
Cell@PDA) cryogel microspheres (400 ± 15 µm) with antibacterial cryogel of sericin-methacryloyl/silver ions
shark skin riblet-inspired wrinkled surface to prevent (SMC@Ag) was fabricated by Zhu et al. based on freeze
acute bleeding within 10 seconds of application [122] . The polymerization of mathacryloyl-modified sericin and
fabricated cellulose microsphere could absorb blood six the in situ reductions of silver ions. The Ag-incorporated
times its weight. Moreover, the microspheres could seal interconnected micropores of the cryogel allows for high
blood loss without applying pressure. A controlled freeze- blood absorption and antibacterial activity in the cryogel.
drying technique customized the surface topology of the The hemostatic efficiency of the fabricated cryogel was
microspheres. Polydopamine (PDA) was incorporated better than commercial gelatin sponge in various in vivo
into the microspheres by in situ polymerization rendering set up, including rat tail amputation, liver injury, and
the microspheres tissue binding ability. Thymol in or on femoral artery injury models. The hemostatic activity of
the microspheres contributed to the antibacterial activity. the SMC@Ag cryogel was attributed to its ability to activate
Upon application of the microspheres on acute bleeding, the coagulation pathway and enhancing the platelet
plasma is instantly drained, and blood components like adhesion during the coagulation process [126] . Injectable,
RBCs, platelets, and coagulation factors are concentrated antibacterial cryogel of chitosan (CS), oxidized gallic acid,
to accelerate the blood coagulation pathway. Wang et al. and hemin (HE) was fabricated by Zhang et al. with high
developed a hyaluronic acid–polyurethane (HA–PU) swelling efficiency upon application to the bleeding wound.
hybrid cryogel that is highly efficient in rapid hemostasis Hemostatic efficiency of the cryogel was attributed to its
and wound healing. The PU emulsion and oxidized HA high absorbency, blood cell and platelet adhesion ability,
were autonomously cross-linked to form the hybrid cryogel and shape recovery. The antibacterial property of the
at -20°C through hydrazine bonding. The surface of the cryogel was observed upon exposure to NIR irradiation.
cryogel comprises macroporous structures of ~220 µm and, The application of the cryogel significantly reduced
upon drying, could shrink up to 1/7 of its original volume. inflammation, improved angiogenesis, and reduced wound
Due to its shape-memory property, the shrunk cryogel healing time [127] . Bai et al. developed a multifunctional

Volume 9 Issue 1 (2023)olume 9 Issue 1 (2023)
V 369 https://doi.org/10.18063/ijb.v9i1.648