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which reduced inflammation and improved tissue generate homogeneous organoid models for achieving
remodeling. In addition, Shi et al. manufactured LHCG high-throughput screening. Owing to its ability of fine-
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and decellularized them to produce dLHCG, which were tuning, multitissue organoids were successfully constructed.
loaded with MSCs and used for rotator cuff repair. The For example, Nguyen et al. established kidney and liver
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biological effects of the stem cell secretomes have been multiorgan microarrays through microfluidics and employed
emphasized, and thus, decellularized stem cell medium can them to investigate the therapeutic potential of extracellular
also be considered a broadly dECM. Chen et al. collected vesicles in diseases. Furthermore, microfluidics provides
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hBMSC-derived mediums and demonstrated that they important support for the regenerative repair process of the
could promote tendon-bone healing in the rotator cuff by rotator cuff. Ding et al. developed hydrogel microrobots
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modulating macrophages. and loaded them with Mg and Zn through a microfluidic
2+
2+
platform to promote the healing of the tendon-bone interface
3.3. Construction techniques and strategies in rotator cuff tears. The microfluidics technology can also
Given the complexity of rotator cuff organoids, it is be used to establish a concentration gradient of cytokines
necessary to synthesize a variety of biotechnologies and to promote gradient differentiation of stem cells and better
methods to better integrate muscle, tendon, and bone recapitulate the structure of rotator cuff. 116
organoids to realize the successful construction of rotator Mechanical stimulation plays a critical role in rotator
cuff organoids and unleash the application potential of cuff healing. Studies have demonstrated that applying
organoids. 3D bioprinting and microfluidics technologies uniaxial strain can induce cellular alignment along the
represent established bioengineering approaches for direction of mechanical loading and enhance ECM
fabricating architecturally complex organoids, while deposition. Furthermore, mechanical loading promotes
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bioreactor systems constitute an emerging strategy with MSCs differentiation, proliferation, and ECM synthesis.
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significant potential. 108
Consequently, applying appropriate mechanical stimulation
3D bioprinting technology enables precise control of during cultivation can facilitate the maturation and
spatial structure and can be employed to fabricate complex functionalization of rotator cuff organoids. For instance,
and highly ordered scaffold structures. Compared with Liu et al. fabricated TFBCs subjected to mechanical
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traditional techniques, 3D printing technology can better stimulation for up to 7 days, which demonstrated superior
mimic the ECM environment, produce layered tissue performance including enhanced cell migration and
structures, and improve organoid performance. Jiang more uniform cell distribution. Mechanical stimulation
et al. generated layer-by-layer scaffolds and three-layer also serves a distinct function in the establishment of
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scaffolds by using polylactic-co-glycolic acid inks through pathological models. For example, building on their
3D printing technology, and combined these scaffolds previous work with trabecular bone organoids, Iordachescu
with stem cells together with hydrogels, which have the et al. successfully established an osteoporosis model
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potential for realizing rotator cuff tendon repair. To further through the application of mechanical stimulation. In
improve organoid performance, the use of cell-loaded addition, mechanical stimulation may promote organoid
dECM bioinks is feasible. Chae et al. designed a gradient vascularization by upregulating proangiogenic factors.
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multi-tissue model by bioprinting using dECM bioinks
containing hBMSCs, which was therapeutically useful for Co-culture serves as a modular assembly strategy.
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rat supraspinatus tendon tears. In addition to this, gene Skardal et al. established an integrated three-tissue
transfection of stem cells by recombinant adenovirus can organ-on-a-chip system through the co-culture of liver,
be synergistically used with 3D printing technology for heart, and lung organoids and applied it to drug screening.
achieving regenerative repair of the rotator cuff tears. 111 Furthermore, innovative techniques such as magnetic-
assisted assembly and acoustic-based assembly have been
Microfluidics is another powerful biomedical explored. Chen et al. demonstrated scaffold-free assembly
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engineering technology for organoid construction, which of organoids using the acoustic node assembly technique.
enables the fabrication of materials with complex adjustable
size, shape, and composition. The cell culture environment 4. Challenges and outlook
can be accurately controlled through the control of flow
rate, viscosity, and other parameters to assist in the high- Rotator cuff organoids hold promising translational
throughput and highly consistent production of organoid potential due to the excellent capabilities of organoid
models. Li et al. employed CTM to dramatically technology and the high prevalence of rotator cuff injuries.
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shorten the construction time of skeletal muscle organoids However, there are still some challenges and obstacles in
the development of rotator cuff organoids.
and achieve large-scale production of functional skeletal
muscle organoids. By using microfluidics and 3D printing Most of the current organoid constructions only
technology, Jiang et al. built an organoid platform to recapitulate partial aspects of the organ’s structure and lack
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Volume 1 Issue 3 (2025) 12 doi: 10.36922/OR025320025