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

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

Samson Prince Hiruthyaswamy  1 , Arohi Bose  1 , Ayushi Upadhyay  1 , Tiasa Raha  1 , Shangomitra Bhattacharjee  1 , Isheeta Singha  1 , Swati Ray  1 , Nazarene Marylene Nicky Macarius  1 , Pragasam Viswanathan  1 , Kanagavel Deepankumar  1
Affiliations
Review

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

Samson Prince Hiruthyaswamy et al. Bioengineered. 2025 Dec.

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.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Cytokine-mediated inflammation and osteophyte formation in OA.
Figure 2.
Figure 2.
Stages of chondrogenesis and key regulatory factors.
Figure 3.
Figure 3.
Fibroblast growth factors in cartilage homeostasis and OA.
Figure 4.
Figure 4.
PI3K/Akt/mTOR pathway in OA.
Figure 5.
Figure 5.
Bone morphogenetic protein signaling in cartilage maintenance and OA progression.
Figure 6.
Figure 6.
Conventional approaches for cartilage regeneration.
Figure 7.
Figure 7.
3D bioprinting approaches for cartilage regeneration.
Figure 8.
Figure 8.
Clinical applications of metallic implants.
Figure 9.
Figure 9.
Development of chitosan based bioproducts in the treatment of OA.
See this image and copyright information in PMC

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