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International Journal of Bioprinting Swelling–shrinking behavior of hydrogel
1. Introduction DA hydrogel, where regulated humidity induced geometric
variations that enabled the opening and closing functions
Recently, three-dimensional (3D) printing has emerged of rhombus-shaped stomata. Dai et al. prepared a
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as a promising technique in tissue engineering and humidity-driven, dynamically colorful display platform via
1,2
regenerative medicine, driving significant advancements material extrusion of PVA hydrogel. The platform’s optical
in the fabrication of in vitro-functionalized tissues and properties could be modulated by the humidity-driven
3,4
organs. Through this additive manufacturing technology, swelling behavior of the hydrogel, enabling a controllable
biomimetic 3D architectures with complex geometric 25
structures can be created using a variety of biocompatible color of the 3D-printed platform. Additionally, Sun et al.
5,6
materials. developed a 3D-printed, flexible humidity sensor with a
composite of carbon nanotubes, polyaniline, and gelatin.
Material extrusion, material jetting, and vat In this system, changes in humidity induced deformation
9,10
7,8
photopolymerization 11,12 are three well-established 3D of the gelatin hydrogel, resulting in detectable variation in
printing technologies for fabricating human-scale organs the electrical resistance of the composite material.
and physiologically relevant disease models. Of these,
material extrusion has garnered increasing attention due Although there is a broad consensus that humidity
to its cost-effectiveness and ease of operation. 13,14 The 3D plays a crucial role in 3D-printed hydrogel architectures,
printing process is typically actuated by mechanical force identifying optimal humidity conditions for hydrogel
or pneumatic pressure, and the materials are extruded from 3D printing remains challenging. During the extrusion
a fine nozzle. Well-arranged filaments are then deposited process, continuous hydrogel filaments are deposited onto
on a two-axis substrate along a predefined trajectory. 15,16 a plate and remain exposed to ambient air until the 3D
Subsequently, a 3D biomimetic architecture is constructed structure is fabricated. As water constitutes the majority of
through layer-by-layer deposition. hydrogel volume, any variation in moisture content directly
impacts the geometry of the 3D-printed filaments.
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Currently, medical-grade biodegradable hydrogels
have become well-acclaimed bio-inks adopted in material When 3D printing occurs under inappropriate ambient
extrusion. These hydrogels closely mimic the biochemical humidity, the concentration of water in the ambient
17
and physical properties of the native extracellular matrix, air is remarkably lower than that within the hydrogel
offering advantages for regenerative medical applications, filaments. This disparity causes moisture to evaporate from
18
such as excellent biocompatibility, prominent drug- the surface of filaments, as water diffuses outward and
encapsulating capability, and negligible cytotoxicity. This transforms into vapor. The resulting moisture loss leads
19
makes hydrogel materials highly promising candidates for to filament shrinkage. In contrast, if the ambient humidity
developing tissue engineering scaffolds as delivery vehicles is excessively high, moisture from the ambient air may
20
for biologically active substances or cells. diffuse back into the hydrogel, increasing its water content
and causing filament swelling. Such humidity-driven
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However, as hydrogels are water-insoluble 3D geometric variations often cause deviations from the
polymeric networks that retain large volumes of fluid, predefined 3D-printed filaments. These cumulative errors
they demonstrate pronounced humidity-driven swelling– during layer-by-layer deposition can lead to wrinkling
shrinking behavior. A wealth of biodegradable hydrogels, or even collapse of the fabricated architecture, ultimately
21
such as Pluronic F-127 (F-127), poly(ethylene glycol) rendering it unsuitable for medical applications.
diacrylate (PEG-DA), and polyvinyl alcohol (PVA),
demonstrate uncontrollable swelling–shrinking behavior These challenges hinder the reliable fabrication of
when the ambient humidity is unstable. This high biomimetic hydrogel architectures, thereby making the
susceptibility to the ambient humidity variation often manufacture of functional human-scale tissue or organs
leads to unpredictable geometric sizes in 3D bioprinted impractical. To address these problems, efforts have
28
structures, which may alter their physical properties. been made in recent research. For example, Search et al.
29
Therefore, humidity control has emerged as a significant developed a humidity-controlled chamber capable of
parameter in hydrogel-based 3D printing. For example, maintaining constant humidity levels from 25 to 80%,
Chang et al. fabricated a multicomponent 3D structure enabling more stable hydrogel 3D printing conditions.
22
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of micro-vessel fragments using F-127 with a material Matamoros et al. prepared an atmospheric chamber
extrusion device and highlighted humidity as a significant to accommodate a self-designed 3D printing device, in
parameter in ensuring the precise deposition of hydrogel which humidity was precisely controlled to maintain
and maintaining the structural fidelity of printed the geometry of the 3D-printed architectures. Likewise,
architectures. Similarly, Lv et al. created a 3D-printed Yu et al. proposed a humidity-controlled enclosure
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architecture with stomata-like microstructures using PEG- for regulating ambient humidity distribution during
Volume 11 Issue 4 (2025) 410 doi: 10.36922/IJB025220222