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

single-component polymeric hydrogel of dopamine- The self-healing and adhesive properties were attributed
modified poly(L-glutamate) with graphene oxide for rapid to the hydrogen bond and metal-ligand coordination
hemostasis and scarless wound healing. The hydrogel provided by the copper ion and carboxyl groups. An
formation relied on oxidative catechol-crosslinking increased concentration of Cu in the fabricated hydrogel
2+
and catechol–carboxyl hydrogen bonding interactions. was reported to inhibit the growth of S. aureus and E. coli
The resulting negative charge in the hydrogel rendered within 3 hours of incubation. The antibacterial efficiency
multifunctionality, including resistance to temperature, of the hydrogel was contributed by the ability of the Cu 2+
urea, and salt. Additionally, the hydrogel showed self- to destroy bacterial cell membranes and alter protein and
healing ability, injectability, desired adhesiveness, and enzyme structures [137] . Yu et al. developed supramolecular
detachability. The polymeric hydrogel could stop bleeding thermo-contracting adhesive hydrogel effective against
with 1.4% blood loss within 12 seconds [128] . An analysis MRSA infection during wound healing. The antimicrobial

of advantages and disadvantages of some other reported hemostat was fabricated via host–guest interaction using
hemostats is given in Table 4. quaternized chitosan-graft-β-cyclodextrin, adenine, and
polypyrrole nanotubes. The multifunctionality of the
6. Antimicrobial hemostats developed hemostat could achieve significant hemostasis

An ideal hemostat with excellent antimicrobial properties and subsequent wound healing within 24 hours post-
[138]
is highly desirable for wound healing applications. surgery . Liang et al. reported the development of
Hemostatic materials can be functionalized with various multifunctional hydrogel dressing comprising numerous
antimicrobial drugs, metal nanoparticles, cationic functional materials, rendering it great adhesive property,
antimicrobial polymers, or antimicrobial peptides for antibacterial efficiency, antioxidative ability, conductivity,
long-term antimicrobial effect [129,130] . Most antimicrobial pH/glucose dual-responsive drug release properties, and
[139]
agents kill the bacteria through cell wall disruption, effective against athletic diabetic foot wounds . All the
membrane perforation, reactive oxygen species (ROS) hydrogels mentioned above hold numerous possibilities
generation, or ion leakage [129] . Photothermal antimicrobial for clinical application and improvement in the healthcare
agents exhibited hyperthermia-induced ROS generation unit.
and killing of bacterial pathogen [131] . For example, silver 7. Conclusion
nanoparticle-doped alginate/chitosan hydrogel has
been shown to promote diabetic wound healing, rapid This review expounds various ways of utilizing micro/
hemostasis, and strong anti-bactericidal efficacy against nanostructures for hemostatic applications in different
Escherichia coli and Pseudomonas aeruginosa [132] . cases, including civilian settings and instances of heavy
and complex surgeries . Recent advances in 3D
[66]
Similarly, cyclohexane-modified N-halamine-doped
chitosan sponge exhibited superior antibacterial effect printing technologies have facilitated the fabrication
of more precise scaffolds for this purpose via various
within 10 minutes against Staphylococcus aureus and micro/nanostructures, including nanotubes, nanofibers,
E. coli. Moreover, the fabricated sponge showed an micro/nanoparticles, micro/nanospheres, and adhesive
extremely low blood clotting index with higher platelet powders/gels. We reviewed how different modeling
adhesion activity [133,134] . Zhou et al. reported that a self- methods, printing materials, and preparation techniques
assembled antimicrobial peptide (jelleine-1) incorporated benefit in unison with 3D and 4D printing technologies.
soft hydrogel to promote rapid hemostasis in a mouse Although electrospinning is the most common pairing
liver injury model with fast blood clotting properties. for 3D/4D printing, it is also possible to combine these
The injectable hydrogel also displayed controlled platelet printing techniques with others such as extrusion
activation, adhesion, and blood coagulation owing to methods, soft lithography, SLA, and DLP-based methods
the presence of the J-1 peptide. Moreover, the fabricated in the construction of novel micro/nanostructures for
hydrogel also showed substantial antibacterial properties rapid hemostasis. Such techniques and applications have
against a broad range of bacteria (methicillin-resistant S. enabled advances in developing and prototyping hydrogel-
aureus [MRSA] and E. coli) and fungi (Candida albicans) [135] . based microfluidic chips [121] , composite hydrogel bio-
Therefore, antimicrobial hemostats can be used as a inks, organs-on-chips, and novel materials for hemostatic
potential alternative to commercial hemostats and provide applications [19,44] .
a favorable environment for platelet adhesion and new
tissue formation with robust antimicrobial properties [136] . We have seen the value of a successful active material
Chen et al. reported the fabrication of adhesive, self- and micro/nanostructure choice for hemostat fabrication.
healing, and antibacterial hydrogel of gelatin methacrylate, The purpose of such a successful material is threefold: (i) to
adenine acrylate, and CuCl for diabetic wound healing. support and enhance the tissue regeneration process at the
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V 370 https://doi.org/10.18063/ijb.v9i1.648
Volume 9 Issue 1 (2023)olume 9 Issue 1 (2023)