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

Mesoporous organosilicon-Polyethyleneimine (MON- into the upper hydrogel layer to simulate cartilage,
PEI) nanoparticles for stable miRNA140-5p transfection, while BMSCs were placed in the lower layer for bone
showing effective cartilage defect repair in a rabbit regeneration. The 3D printing technique enabled precise,
joint model. layer-specific placement of cells, facilitating independent
functionality and spatial alignment of cartilage and bone.
3.4. Cells heterogeneity ACPCs and BMSCs promote cartilage and bone formation
Cell-laden hydrogel 3D printing has gradually drawn through the secretion of specific growth factors and
attention in the last decade. Cells employed for ECM components. Cell–cell interactions simultaneously
osteochondral regeneration include MSCs, such as BMSCs stabilize the cartilage–bone interface, with BMSCs in the
and adipose-derived stem cells (ADSCs), articular cartilage osseous layer driving both bone matrix production and
progenitor cells (ACPCs), and induced pluripotent angiogenesis, thus enhancing nutrient supply. Vascular
stem cells (iPSCs). MSCs show low immunogenicity penetration into the cartilage layer is suppressed by the
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and good in vivo safety, becoming the most widely used cartilage matrix secreted by ACPCs, maintaining low
cell in regenerative medicine. Although technically vascularization within the cartilage.
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pluripotent, MSCs rarely repair damaged tissue in vivo
through direct differentiation and engraftment due to 4. Pivotal properties of scaffolds for
certain limitations, including the reduced capacity of these
cells for self-renewal, proliferation, and differentiation in in vivo application
donor sites. Besides, BMSCs are inclined to differentiate 4.1. Degradation rate
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into bone tissue rather than cartilage. 118,119 Therefore, During osteochondral repair, scaffolds must provide
scaffolds require the modulation of differentiation through temporary and adequate mechanical support to the
cytokines or drugs. However, the side effects associated defect site while degrading at a controlled rate to allow
with cytokines, combined with their high costs, present regenerated tissue to replace the scaffold and integrate with
significant limitations for their clinical use in vivo. For surrounding tissue. In vivo, osteochondral regeneration
example, although TGF-β is proven to induce chondral typically progresses through the following stages : (1)
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differentiation, Zhen et al. reported that overactivation the inflammatory stage, where immune cells remove dead
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of the TGF-β1 pathway in subchondral bone may cells from the damaged tissue to establish a foundation
lead to pathological changes associated with cartilage for regeneration; (2) the proliferating stage, lasting
degeneration. Furthermore, the release kinetics and half- approximately 2–6 months, during which endogenous
life of small molecules in vivo restrict their long-term cells migrate to the injury site as the scaffold degrades,
therapeutic efficacy. Therefore, a bicellular scaffold could proliferate, differentiate, and gradually replace the scaffold;
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be a promising approach for tissue regeneration. Bicellular and (3) the remodeling stage, during which the biophysical
scaffolds enable precise spatial cell alignment by delivering properties of the newly formed tissue further enhance
the cells during the printing process, rather than relying on and replace the scaffold to become the predominant load-
intrinsic cell migration. Furthermore, the bicellular system bearing component. This stage could last several months.
enhances tissue function and structural reconstruction Throughout the process, the biophysical properties of the
through cell–cell interactions, enabling the synchronous newly formed tissue improve as the scaffold’s mechanical
repair of different tissues. 63 support diminishes, establishing a dynamic balance that

Möller et al. demonstrated that co-encapsulation of preserves the mechanical stability of the osteochondral
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hBMSCs and human nasoseptal chondrocytes (hNCs) tissue. Therefore, the degradation kinetics of scaffolds
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within GelMA hydrogels for 3D bioprinting resulted in must synchronize with tissue growth. Meanwhile, since
more pronounced ECM deposition compared to hBMSCs bone has higher mechanical support requirements than
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alone. Wu et al. developed a bicellular 3D-printed liver cartilage, the degradation rate of bone-phase scaffolds is
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lobule-mimetic structure, demonstrating that the HepG2 + typically slower than that of cartilage-phase. In vitro studies
NIH/3T3 bicellular system enhanced HepG2 proliferation reveal that the cartilage phase degrades almost completely
and function compared to monocellular systems, which can within approximately 12 weeks, aligning with cartilage
be attributed to crosstalk pathways via NIH/3T3-secreted regeneration, while bone-phase scaffolds require a longer
cytokines and growth factors. The bicellular model better degradation period, typically 16–24 weeks or more. 47,48,54
mimics the physiological microenvironment, improving The degradation rate of scaffolds is influenced by
cell–cell/matrix interactions and enhancing functionality. multiple aspects, including chemical composition,
Zhang et al. developed a bicellular anisotropic hydrogel geometric structure, porosity, and microenvironment.
scaffold using 3D printing. ACPCs were incorporated Blending two or more polymer materials is a common

Volume 11 Issue 4 (2025) 15 doi: 10.36922/IJB025120100