Molecular signaling pathways in osteoarthritis and biomaterials for cartilage regeneration: a review

Bioengineered. 2025 Dec;16(1):2501880. doi: 10.1080/21655979.2025.2501880. Epub 2025 May 7.

Abstract

Osteoarthritis is a prevalent degenerative joint disease characterized by cartilage degradation, synovial inflammation, and subchondral bone alterations, leading to chronic pain and joint dysfunction. Conventional treatments provide symptomatic relief but fail to halt disease progression. Recent advancements in biomaterials, molecular signaling modulation, and gene-editing technologies offer promising therapeutic strategies. This review explores key molecular pathways implicated in osteoarthritis, including fibroblast growth factor, phosphoinositide 3-kinase/Akt, and bone morphogenetic protein signaling, highlighting their roles in chondrocyte survival, extracellular matrix remodeling, and inflammation. Biomaterial-based interventions such as hydrogels, nanoparticles, and chitosan-based scaffolds have demonstrated potential in enhancing cartilage regeneration and targeted drug delivery. Furthermore, CRISPR/Cas9 gene editing holds promise in modifying osteoarthritis-related genes to restore cartilage integrity. The integration of regenerative biomaterials with precision medicine and molecular therapies represents a novel approach for mitigating osteoarthritis progression. Future research should focus on optimizing biomaterial properties, refining gene-editing efficiency, and developing personalized therapeutic strategies. The convergence of bioengineering and molecular science offers new hope for improving joint function and patient quality of life in osteoarthritis management.

Keywords: CRISPR/Cas9; Osteoarthritis; biomaterials; cartilage regeneration; inflammation; molecular pathways.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials* / chemistry
  • Biocompatible Materials* / pharmacology
  • Cartilage* / physiology
  • Humans
  • Osteoarthritis* / metabolism
  • Osteoarthritis* / therapy
  • Regeneration* / drug effects
  • Signal Transduction* / drug effects

Substances

  • Biocompatible Materials