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International Journal of Bioprinting                             3D-printed scaffolds for osteochondral defect










































                                Figure 1. A schematic diagram of natural gradient classification for osteochondral tissue.


            promote osteochondral regeneration. Li ions have been   sensitive miR-99b regulates the osteogenic and adipogenic
            shown to stimulate chondrogenesis by upregulating   differentiation of BMSCs by targeting the rapamycin
            exosomal miR-455-3p in bone marrow mesenchymal stem   signaling pathway. Similarly, Lai et al.  demonstrated
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            cells  (BMSCs).   Mg  ions  and  Mg  transporter  subtype  1   that substrate stiffness modulates BMSCs proliferation via
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            protein (MagT1)  enhance osteogenic differentiation in   exosome-mediated mechanotransduction through Yes-
            rBMSCs.  Si ions promote angiogenesis by modulating   associated protein (YAP) pathways.
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            the expression of insulin-like growth factor-1 (IGF-1)   Scaffolds with a lower elastic modulus (~10  MPa)
            and VEGF.  However, the use of ceramic materials is   inhibit the regeneration of the SCB while promoting the
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            limited due to their asynchronized degradation relative to   formation of fibrous tissue at the articular interface. In
            bone regeneration. 77
                                                               contrast, scaffolds with a higher elastic modulus (~1000
               Due to the zonal mechanical strength of normal   MPa) may compress the opposing cartilage, leading to
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            cartilage, which is adapted to different functions, providing   its degradation.  Consequently, scaffolds with biphasic
            layered mechanical support during the repair process and   mechanical  properties  have  been  extensively  studied
            achieving biomimetic repair outcomes are crucial. It has   to improve the healing of both bone and cartilage.
            long been established that the growth of both cartilage   Diloksumpan et al.  developed a triple-layer scaffold using
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            and bone tissues, both in vivo and in vitro, is influenced   extrusion-based printing and melt electrospinning writing
            by the surrounding mechanical strength. 78,79  Cells can   (MEW). The top chondral layer consists of a PCL mesh
            sense and respond to variations in substrate stiffness,   infused with GelMA hydrogel, while the middle layer,
            thereby regulating their diffusion, proliferation, and   composed of a PCL mesh and polymer-calcium phosphate
            gene expression.  Yang et al.  fabricated HAp and PEG/  (PCaP) composite, is designed to replicate the structure
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            SF composites with different stiffness levels and induced   of calcified cartilage for chondral-osseous transition. The
            osteogenesis in rBMSCs, revealing a positive correlation   osseous layer is fabricated from PCaP. Each layer was
            between stiffness and the expression of osteogenic   designed to adapt to its specific mechanical demand. Gao
            markers. Cao et al.  demonstrated that the matrix stiffness-  et al.  established a bilayer scaffold based on GelMA, where
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            Volume 11 Issue 4 (2025)                        8                             doi: 10.36922/IJB025120100
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