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microstructural interactions between collagen fibers and filaments or fibers. Wet-spinning is highly effective for
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soft proteoglycans. The resulting anisotropic composite producing fibers with larger diameters (tens to hundreds
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hydrogel exhibited high mechanical performance of micrometers) and high mechanical strength, making
comparable to native tendons while maintaining a water it suitable for generating bundles or yarns that better
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content of approximately 60%, similar to actual tendon mimic the fascicular structure of tendons. By controlling
tissue. Composite hydrogels combine biocompatibility the coagulation kinetics and applying post-stretching,
with ideal mechanical properties, and their performance significant alignment and enhanced mechanical properties
can be precisely tuned by adjusting the proportions of their can be imparted to the fibers. Aligned wet-spun fiber
components. The strategy of constructing organoids using bundles have been used as core scaffolds to guide tenocyte
hydrogels has been successfully applied to the development alignment and promote organized ECM deposition. 133,134
of various organoids, including cartilage organoids. Wet spinning facilitates the fabrication of highly
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Notably, recent work by Zhang et al. further underscores biocompatible fibers by avoiding the use of toxic reagents
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the potential of 3D hydrogel systems for constructing during the spinning process; however, compared with
tendon organoids. By encapsulating TSPCs in a collagen- those in electrospinning scaffolds, it may be challenging to
hyaluronic acid composite hydrogel, their study revealed attain desirable mechanical properties for the as-prepared
that the 3D microenvironment dynamically regulates TSPC fibers. Electrohydrodynamic Jetting is an advanced
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subpopulations via FGF7-mediated mechanosignaling, form of electrospinning that employs precise control over
demonstrating the potential of hydrogel in constructing the jetting process using a smaller nozzle and lower flow
tendon organoids. rates. This level of spatial control surpasses traditional
random electrospinning and allows for the fabrication of
Native tendons possess a highly organized, aligned 135
fibrous structure, making the architectural design of scaffolds with complex, predefined architectures, that can
meticulously replicate specific tendon tissue geometries or
scaffolds critical for mimicking the spatial organization create tailored mechanical microenvironments. It offers
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of the actual cellular microenvironment. To replicate exceptional precision for patterning bioactive molecules or
this complex structure, a variety of advanced fabrication multiple cell types within the scaffold. However, the process
techniques have been developed and applied in tendon can be slower than bulk electrospinning and requires
tissue engineering and the construction of organoids. sophisticated control systems.
Electrospinning techniques utilize a high-voltage electric The selection of the optimal fabrication technique
field to draw polymer solutions or melts into ultrafine depends on the specific design goals for the tendon organoid,
fibers collected on a grounded target. This technique balancing factors such as the required fiber diameter/
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enables the fabrication of scaffolds composed of aligned alignment, mechanical strength, structural complexity
microfibers specifically designed to replicate the diameter (2D vs. 3D), resolution, biomimicry level, porosity, and
range (typically 1–20 µm) and oriented arrangement integration with cells/biomolecules. Combining techniques
of collagen fibers found in natural tendons. 129,130 This is also a promising strategy to leverage their respective
dimensional and architectural mimicry is crucial, as it strengths. 116,136,137
promotes directional cell growth, enhances functional
expression (e.g., tenogenic marker production and ECM 4.3.2. Mechanical stimulation
alignment), and has been employed in numerous studies The physiological function of tendons is highly dependent
of tendon tissue engineering. Nanofiber scaffolds fabricated on their mechanical properties. Studies have shown
using electrospinning techniques can replicate the aligned that the response of tendon cells to mechanical stress
fiber arrangement of natural tendons, 130,131 promoting significantly influences their phenotype and function.
directional cell growth and functional expression. Adjusting Cyclic mechanical stretching promotes collagen synthesis
the porosity (60–90%) of scaffolds facilitates uniform and tenogenic differentiation in tendon cells, 131,138 enhances
cell distribution, nutrient diffusion, and vascularization, the alignment of the ECM, and improves the mechanical
addressing the mass transport design requirement. In properties of tendon organoids. Research investigating
addition, nanoscale roughness or microgroove structures the effects of mechanical deprivation on tendons has
can guide cell alignment and differentiation, enhancing the demonstrated that mechanical stimulation plays a
mechanical properties of tendon organoids. While powerful critical role in the formation of fibril bipolar structures
for creating 2D mats or thin 3D structures, achieving thick, and collagen remodeling. Furthermore, mechanical
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truly 3D constructs with deep cellular infiltration remains stretching on 3D simulated scaffolds has been shown
a challenge with standard electrospinning. 132 to promote the expression of tenocyte phenotypes. In
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Wet-spinning involves extruding a polymer solution addition to bioreactors for applying mechanical stimuli,
through a spinneret into a coagulation bath, causing the microfluidic systems can simulate in vivo hydrodynamic
polymer to precipitate or solidify, forming continuous environments, providing precise mechanical stimulation
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Volume 1 Issue 3 (2025) 10 doi: 10.36922/OR025170016