Background <p>Cartilage has limited self-repair capacity, making it vulnerable to damage from aging, trauma, or mechanical stress, which can progress into severe joint disorders. Stem cell-based therapies offer a promising solution for cartilage regeneration and the development of transplantable cartilage constructs.</p> Methods <p>This review highlights recent advances in stem cell <i>in vitro</i> chondrogenic differentiation and their therapeutic applications. It explores various stem cell sources and the mechanisms guiding chondrogenesis, including dynamic culture conditions, differentiation via intermediate lineages, biomaterial scaffolds, and genetic or epigenetic modulation.</p> Results <p>Results:&#xa0;The roles of small molecules and growth factors in directing stem cells toward functional chondrocytes are also discussed. Additionally, we briefly examine the emerging integration of artificial intelligence (AI) in cartilage tissue engineering. AI applications such as predicting differentiation outcomes, monitoring chondrogenic progression in real-time, and identifying small-molecule enhancers are poised to accelerate discovery and standardization in the field.</p> Conclusion <p>The review concludes with an analysis of current limitations and translational challenges that should be addressed to obtain the clinical potential of stem cell-derived chondrocyte therapies.</p> Graphical Abstract <p>Schematic representation of stem cell types and differentiation strategies for chondrocyte formation in cartilage regeneration. This figure was created with BioRender.com, accessed in May 2025.</p>

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Chondrogenic Differentiation of Stem Cells for Cartilage Regeneration: Advances and Future Perspectives

  • Ahmed Abdal Dayem,
  • Abdelbary Prince,
  • Ahmed M. M. Gabr

摘要

Background

Cartilage has limited self-repair capacity, making it vulnerable to damage from aging, trauma, or mechanical stress, which can progress into severe joint disorders. Stem cell-based therapies offer a promising solution for cartilage regeneration and the development of transplantable cartilage constructs.

Methods

This review highlights recent advances in stem cell in vitro chondrogenic differentiation and their therapeutic applications. It explores various stem cell sources and the mechanisms guiding chondrogenesis, including dynamic culture conditions, differentiation via intermediate lineages, biomaterial scaffolds, and genetic or epigenetic modulation.

Results

Results: The roles of small molecules and growth factors in directing stem cells toward functional chondrocytes are also discussed. Additionally, we briefly examine the emerging integration of artificial intelligence (AI) in cartilage tissue engineering. AI applications such as predicting differentiation outcomes, monitoring chondrogenic progression in real-time, and identifying small-molecule enhancers are poised to accelerate discovery and standardization in the field.

Conclusion

The review concludes with an analysis of current limitations and translational challenges that should be addressed to obtain the clinical potential of stem cell-derived chondrocyte therapies.

Graphical Abstract

Schematic representation of stem cell types and differentiation strategies for chondrocyte formation in cartilage regeneration. This figure was created with BioRender.com, accessed in May 2025.