Gene Therapy and Tissue Engineering for Cartilage Regeneration

Cartilage regeneration remains a formidable clinical challenge owing to the intrinsic avascularity, limited cell turnover and complex extracellular matrix of articular cartilage. Gene therapy and tissue engineering are converging to address these hurdles through precisely controlled delivery of genetic material, cells and biomaterial scaffolds. Gene therapy approaches harness viral or non-viral vectors to introduce or edit genes that encode key chondrogenic factors, anti-inflammatory cytokines or matrix-modulating enzymes, thereby directing cell behaviour in situ. Tissue engineering complements this by providing three-dimensional scaffolds—often hydrogels or composite biomaterials—laden with progenitor or stem cells and bioactive molecules. Together, these strategies aim to recreate the zonal architecture of native cartilage, support chondrocyte proliferation and matrix synthesis, and integrate with the subchondral bone. Recent advances include development of self-healing, gene-activated hydrogels for sustained microRNA release, genome editing of inflammatory pathways to attenuate osteoarthritic lesions and thermosensitive carriers for site-specific viral vector delivery. As these technologies mature, they hold promise for off-the-shelf or minimally invasive therapies that restore joint function and delay or obviate the need for arthroplasty.

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Gene Therapy and Tissue Engineering for Cartilage Regeneration publication trend

The graph below shows the total number of articles in gene therapy and tissue engineering for cartilage regeneration across all publications each year (not limited to Nature Index journals).

Technical terms

Gene therapy: Introduction or editing of genetic material to modulate cellular functions or protein expression.

Tissue engineering: Integration of cells, scaffolds and bioactive molecules to reconstruct or repair damaged tissues.

Articular cartilage: Smooth, load-bearing connective tissue covering joint surfaces, characterised by low vascularity and specialised matrix.

Hydrogel: Hydrated polymer network that mimics extracellular matrix and supports cell infiltration and factor release.

Viral vector: Engineered virus used to deliver therapeutic genes into target cells with high efficiency.

Mesenchymal stem cells (MSCs): Multipotent stromal cells capable of differentiating into chondrocytes, osteoblasts or adipocytes.

CRISPR-Cas: Genome-editing system that enables precise DNA modification by programmable nucleases.

MicroRNA: Small non-coding RNA that regulates gene expression post-transcriptionally by targeting mRNA.

References

1. Self‐Healing Hyaluronic Acid‐based Hydrogel with miRNA140‐5p Loaded MON‐PEI Nanoparticles for Chondrocyte Regeneration: Schiff Base Self‐Assembly Approach. Advanced Science (2024).
2. Emerging technology has a brilliant future: the CRISPR-Cas system for senescence, inflammation, and cartilage repair in osteoarthritis. Cellular & Molecular Biology Letters (2024).
3. Thermosensitive Hydrogel Based on PEO–PPO–PEO Poloxamers for a Controlled In Situ Release of Recombinant Adeno‐Associated Viral Vectors for Effective Gene Therapy of Cartilage Defects. Advanced Materials (2019).