Physical characteristics and chondrogenic differentiation of mesenchymal stem cells on freeze-dried bovine cartilage sponge in bioreactor culture: A systematic review and meta-analysis

Articular cartilage has limited intrinsic repair capacity, and static culture of scaffolds fails to replicate the physiological microenvironment. Freeze-dried bovine cartilage sponge (FDBCS) supports mesenchymal stem cell (MSC) growth, but dynamic bioreactor conditions may further enhance chondrogenesis. A systematic review and meta-analysis were performed according to PRISMA guidelines, including PubMed, Cochrane CENTRAL, and ScienceDirect (2020–2025). Outcomes were sulfated glycosaminoglycan (sGAG) content, gene expression (SOX9, COL2A1, COL10A1, MMP13), and scaffold morphology. Four in vitro studies met inclusion. Bioreactor culture significantly increased sGAG (SMD 4.42; 95% CI 2.46–6.38; I 2 =0%) and SOX9 (SMD 2.05; 95% CI 0.66–3.43). COL10A1 expression was elevated (SMD 2.82; 95% CI 1.69–3.95), whereas COL2A1 and MMP13 results were inconsistent. Dynamic culture improved cell distribution, extracellular matrix deposition, and proteoglycan retention compared with static culture. Bioreactor-based FDBCS scaffolds enhance MSC chondrogenesis and scaffold quality. However, increased hypertrophic marker expression highlights the need for optimized mechanical parameters and culture duration. Standardization and in vivo validation are required for clinical translation.