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3.1.2. ADSCs resulting organoids. Matrigel is the basic matrix material
for organoid construction, but due to the complexity of
Although BMSCs remain the primary cell source, the its composition and poor mechanical properties, a variety
utilization of ADSCs has gradually broadened due to their of new and personalized matrix materials are gradually
ease of accessibility, simple isolation process, and high being developed, including natural hydrogels, synthetic
proliferation efficiency. For example, Shi et al. loaded hydrogels, and dECM. In the following, we will introduce
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ADSCs together with human amniotic membrane MSCs matrix materials that can be used for rotator cuff organoid
(hAMSCs) onto decellularized activated living hyaline construction.
cartilage grafts (LHCG) and implanted them into rat
models, which achieved the repair of tendon-bone interface 3.2.1. Hydrogel
and promoted the healing of RCI. Meanwhile, this study
also provided preliminary evidence of the feasibility of Hydrogels are matrix materials with biomimetic properties
hAMSCs for rotator cuff organoid construction. In addition, that have controlled mechanical properties, porosity,
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interestingly, Song et al. concluded that the frozen ADSC and viscoelasticity compared with natural extracellular
matrices, which can promote cell adhesion, migration,
slices are off-the-shelf scaffold that can efficiently repair and proliferation differentiation. Due to its excellent
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rabbit supraspinatus tendon tears. Similarly, Shin et al. properties, hydrogel plays an important role in organoid
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effectively repaired rotator cuff tears by employing cell construction and tissue repair, and has also been used for
slices prepared using ADSCs and transplanting them to the rotator cuff repair. Ni et al. developed a PCL scaffold with
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tear site. In addition, Fu et al. demonstrated that hydrogel the help of 3D printing technology and loaded the scaffold
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scaffolds containing ADSC-derived exosomes could with BMSCs and basic fibroblast growth factor, which was
regulate the growth and differentiation of TDSCs, thereby then implanted into rat supraspinatus tendon tear sites
promoting the healing of rotator cuff injuries. to enhance the interfacial healing of rotator cuff injuries.
3.1.3. TDSCs Hydrogels offer exceptional utility in stem cell delivery
due to their adjustable physical and chemical properties.
Compared to other stem cells, TDSCs exhibit a more Dai et al. used gelatin methacrylate (GelMA) to deliver
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mature tendon phenotype, while demonstrating powerful ADSCs with porous Se@SiO nanoparticles. The composite
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proliferation and differentiation capacities, which make construct was subsequently implanted into the rat tendon-
this cell type an ideal cell type for tendon regeneration. bone interface, not only to minimize the loss of stem cells,
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Central to RCI repair is the repair of the tendon-bone but also to promote the repair of RCI. Similarly, Yuan et al.
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interface, and TDSCs also serve as potential cell sources employed porous hyaluronic acid methacrylate hydrogel to
for rotator cuff organoid construction. For example, He encapsulate ADSCs and BMP2 and used it for RCI repair
et al. found that TDSC-derived exosomes could modulate in rats, achieving fibrocartilage reconstruction and thus
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inflammation and improve the structure and function of promoting repair. Given the transitional, layered structure of
the tendon-bone interface. Then, they loaded the exosomes the tendon–bone interface, multiphase scaffolds combined
onto type I collagen and polydopamine-modified scaffolds, with hydrogels have emerged as a more complex yet more
and subsequently implanted these scaffolds into the torn faithful strategy for mimicking the natural tissue hierarchy.
supraspinatus muscle of rats, which led to more enhanced Cao et al. generated multiphase scaffolds to recapitulate
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reparative effects and lower inflammatory response the transitional interfacial structure of the rotator cuff
compared with control group and rats receiving only through 3D printing, and encapsulated fibroblasts, BMSCs,
scaffold implantation treatment. Zhang et al. achieved and osteoblasts hierarchically in GelMA, thus constructing
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rotator cuff repair in rabbit rotator cuff tear models by a cell/GelMA-multiphase scaffold composite, which has
employing PCL-based 3D-bioprinted scaffolds loaded with substantial potential in rotator cuff repair.
TDSC-derived exosomes together with type I collagen,
and the composite scaffolds could promote the migration, 3.2.2. Decellularized ECM
proliferation, and differentiation of BMSCs. Within natural tissues, the ECM fulfills critical functions
such as offering mechanical support, mediating signaling
3.2. Matrix materials
cascades, and providing adhesion. As a result, animal-
Matrix materials play a pivotal supporting role in the derived ECM scaffolds have been approved for use in
construction of rotator cuff organoids by mimicking valve replacement, orthopedic implants, hernia repair, and
the natural tissue microenvironment and inducing cell other areas. Decellularized ECM derived from human or
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growth, proliferation, migration, and differentiation, animal sources has been successfully used in the generation
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thus optimizing the structural function of rotator cuff of various organoid models. Chin et al. treated fascial
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organoids. Good matrix materials also contribute to the ECMs with high-molecular-weight tyramine, instead of
superior mechanical properties and biocompatibility of the hyaluronic acid, and implanted them into rat models,
Volume 1 Issue 3 (2025) 11 doi: 10.36922/OR025320025

