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International Journal of Bioprinting 3D-printed EVs for nasal septal defects

approximate diameter of 1 μm, consistent with previous of the composite scaffold were measured. The results
reports. Chondrocytes can be observed attaching to demonstrated that the composite scaffold exhibited strong
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fibers and displaying a similar round-like structure in tensile ductility and high compressive modulus, indicating
vivo under SEM. This observation confirms that the sufficient mechanical strength to effectively support
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PLGA scaffold effectively mimics the extracellular matrix the defected part. The stable structure of the composite
of chondrocytes, thereby facilitating chondrocyte growth stent facilitated effective filling of the defect site without
and proliferation. The porous surface and hydrophilic compromising nasal ventilation, i.e., no impairment of
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properties of GelMA hydrogel promote chondrocyte ventilation was observed in the rabbits. Cartilage defect
adhesion, while its extracellular matrix components repair is closely linked to chondrocytes. Like other hyaline
support cartilage formation and deposition. Additionally, cartilage, the nasal septal cartilage has a lower cell content
swelling experiments demonstrated that the scaffold and weaker repair ability. During cartilage repair, the
efficiently absorbs blood and other body fluids. The formation of essential extracellular matrix components,
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sustained-release ability is crucial for evaluating stent such as Col II and ACAN, is primarily dependent on
suitability. GelMA hydrogel, due to its capacity for sustained chondrocytes. Therefore, promoting the generation of
release at defect sites and strong self-decomposition of chondrocytes in the defect tissue becomes essential for
EVs, is a commonly used biomaterial in cartilage tissue successful repair. Our study demonstrated that EVs
repair. Our experimental findings indicate that composite can effectively enhance chondrocyte proliferation and
scaffolds slowly release EVs over 14 days. Furthermore, the migration. Likewise, the addition of EVs improves the
literature suggests that high concentrations of EVs exert ability of chondrocytes to secrete the extracellular matrix.
high osmotic pressure, which enhances their diffusion in Additionally, we found that chondrocytes secrete Col II in
the medium. As EV concentrations decrease, their release response to EV stimulation, and ACAN expression was
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rate also slows down. gradually enhanced. In vivo Col II immunohistochemistry
Due to their abundant protein and nucleic acid revealed that the addition of EVs promoted collagen
content, EVs are widely used in the repair of various deposition, further accelerating tissue repair.
tissues and organs. Most studies indicate that researchers In this experiment, we utilized 3D EVs with varying
still use traditional EV preparation methods, typically concentrations to investigate the functional roles of EVs in
involving extraction from a 2D environment, i.e., by cells. Our previous study revealed that lower concentrations
collecting the medium of adherent cells in a petri dish of 3D EVs had a positive promotes proliferation,
for ultracentrifugation. This method of extracting migration, and extracellular matrix production on cells.
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EVs is time-consuming and tedious, and the final yield However, we observed that high concentrations of EVs
is often low. Based on the results of previous studies, inhibited cell proliferation, migration, and the expression
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we used stem cell EVs cultured in a 3D environment to of related genes. These findings are novel and have been
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conduct the present study. Coaxial printing was utilized rarely reported. EVs are small molecules that facilitate
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for the encapsulation of EVs in hydrogels to mimic the intercellular communication, regulating cell behavior
3D cellular environment both in vivo and in vitro. EVs within organisms. However, the effectiveness of EVs in
collected within a 3D environment demonstrate higher organisms does not necessarily increase with higher doses.
productivity and lower cost consumption compared to When the concentration of EVs exceeds a threshold, it
those collected from a 2D setting. Additionally, proteomic may induce an inhibitory effect on the relevant cellular
analysis and other studies have demonstrated that 3D functions. This phenomenon helps explain certain
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EVs exhibit superior effects compared to traditional 2D observations from previous experiments, though further
EVs. 44,45 In this study, we conducted a simple functional exploration is warranted to fully understand the specific
comparison of chondrocytes using 2D and 3D EVs. causes of inhibition. Previous studies have indicated
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Our preliminary findings indicate that 3D EVs are more that 3D EVs are more effective than 2D EVs in promoting
effective at promoting cell proliferation and migration. skin defect healing and treating burns. 48,49 The present
Hence, we have selected 3D EVs as the primary focus for study builds on previous research findings where 3D EVs
subsequent experiments. facilitate the treatment of nasal septum injury. However,
Although the cartilage in the nasal septum does not the enhancement mechanism of 3D EVs remains unclear,
bear the same load as knee or vertebral articular cartilage, and this will be the focus of our subsequent research. It is
its collapse can significantly impact a patient’s appearance. known that EVs derived from different tissue cells exhibit
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Therefore, any implanted material must possess specific specific effects, allowing for targeted treatment of diseases.
mechanical properties to adequately support the defect. Additionally, recipient cells may exhibit varying sensitivity
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In this experiment, the tensile and compressive modulus to stem cell-derived EVs. Therefore, leveraging our

Volume 10 Issue 6 (2024) 189 doi: 10.36922/ijb.4118