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

wound or defect site; (ii) to degrade in situ with minimal Therefore, to achieve the best biodegradable and bioactive
adverse effects; and (iii) to eventually get replaced with the effects compatible with typical human physiology, it is
body’s own newly generated tissue. Therefore, to increase imperative to elucidate the structure and composition of
the biofunctional potential of these novel agents, there is the ECM to develop more efficient and effective micro/
a need to fabricate scaffolds that can recreate the micro/ nanostructures [146] .
nanoscale topographical landscape while considering
the role of bioactive factors that react to cues from the 8. Future prospects
extracellular environment [6,14,140] . For this purpose, we have
specifically designed and seamlessly integrated micro/ There are many advantages to utilizing micro/nanostructures
nanostructures into multilayered scaffolds because of for hemostasis and wound healing applications. We can
their inherent ability to closely reflect the body’s natural combine novel technologies such as 3D/4D printing and
physiologic processions in injured tissues . electrospinning to fabricate biomimetic hemostatic agents
[37]
that assist the body’s natural regenerative responses when
To further elucidate these bioactive interactions between it cannot do so on its own. Because of this, 3D/4D printing
material properties and behavior, computational models and techniques are a significant step in advancing from generalized
high-throughput experimentation can serve as a potential administration of medications and therapy to personalized
tool to accelerate the development of high-performance therapy for hemostasis and wound healing applications [7,147] .
materials and confirm micro/nanostructure interactions in We can potentially bring the benefits of efficient and
the cell–matrix interface [141,142] . Other applications include effective cellular and molecular healing techniques via
using a nonlinear finite element code analysis to conduct micro/nanostructures to civilian and surgical settings
simulations to study the mechanics of submicron pillars where wounds, surgery, and even hemophilia are relatively
and cell interaction when considering different substrates common. We will continue to develop more effective and
as potential high-performance materials [6,143] . targeted hemostatic agents for more biomimetic, patient-

One of these high-performance materials for specific therapies using the combined technologies, active
hemostasis and wound healing is hydrogels. Hydrogels biomolecules and mediators, stimulus responsivity, and
have the inherent advantages of injectability, self-healing, biophysical signaling applications available to supplement
and remodeling. We can combine them with printed the design of micro/nanostructures.
micro/nanostructures for rapid hemostasis promotion However, there remains a shortage of information on
and an overall biomimetic wound healing effect. When the mechanisms of action and progression of in situ cell
designed together with stimulus-responsive capabilities, behavior, mainly owing to the shortage of detection tools
such as pH and ROS sensitivity , these novel hydrogel to precisely monitor cell behavior in internal conditions.
[41]
constructs gain the ability to realize sequential and on- Thus, research teams are striving to enable the detection
demand drug delivery [74,144] . Additionally, the surface of bio-relevant analytes for such signaling purposes by
topographical features and chemical composition of incorporating micro/nanostructures into sensing systems.
micro/nanostructures, such as biodegradable CNFs, can be For example, a 2020 study by García‐Astrain et al. [148]
further documented to develop advanced design strategies described the potential of using a surface-enhanced
for more effective hemostatic products with on-demand Raman scattering (SERS) spectroscopy within a plasmonic
drug delivery capabilities for future clinical use . hydrogel-based, 3D-printed scaffold to this end. These
[37]
This sequential and on-demand drug delivery has been SERS-active scaffolds allow for the 3D detection of model
made possible by recent advancements in tissue engineering molecules and biomarkers and offer great flexibility in
and regenerative medicine and elucidating the beneficial selecting plasmonic nanoparticles. Additionally, this
effects of micro/nanostructures. Recently, we have seen study proved the possibility of using these plasmonic
much growth in the development of multifunctional scaffolds for SERS sensing of cell-secreted molecules over
intelligent materials for advanced therapeutic extended periods by detecting the biomarker adenosine
[148]
applications [145] . Currently available technologies allow us for biosensing applications . Other studies have
to accurately and precisely mimic distinct characteristics highlighted different methods of triggering local sensing
in the in situ microenvironment using different materials based on micro/nanostructures’ stimulus-responsive
[147]
and development methods for user-tunable micro/ capacities using external signals, such as light via laser ,
[89]
nanostructures. In vivo tissue architecture is very complex temperature , ultrasound, or an applied magnetic field.
and dynamic, as there is much interconnectivity between Such a biosensing method is crucial to advancing
cells and specific components of the extracellular matrix . wound healing technologies because foreign-body
[18]

Volume 9 Issue 1 (2023)olume 9 Issue 1 (2023) 372 https://doi.org/10.18063/ijb.v9i1.648
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