Chondrogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells in a Perfused Collagen Hydrogel Functionalized with hTGF-β1-Releasing PLGA Microcarrier

Tissue engineering strategies can be relevant for cartilage repair and regeneration. A collagen matrix was functionalized with the addition of poly-lactic-co-glycolic acid microcarriers (PLGA-MCs) carrying a human Transforming Growth Factor β1 (hTFG-β1) payload, to provide 3D biomimetic environment capacity direct stem cell commitment towards chondrogenic phenotype. PLGA-MCs (mean size 3 ± 0.9 μm) were prepared via supercritical emulsion extraction technology tailored sustain delivery payload into hydrogel 21 days. coseeded Bone Marrow Mesenchymal Stem Cells (hBM-MSCs) in matrix. Chondrogenic induction suggested when dynamic perfusion applied as indicated by transcriptional upregulation COL2A1 gene (5-fold; p < 0.01) downregulation COL1A1 (0.07-fold; 0.05) COL3A1 (0.11-fold; genes, at day 16, monitored qRT-PCR. Histological quantitative-immunofluorescence (qIF) analysis confirmed activity remodeling synthetic extracellular cultured perfused conditions. Static constructs lacked evidence specific overexpression, which probably due reduced mass exchange, determined system Finite Element Modelling (FEM) analysis. Proinflammatory (IL-6, TNF, IL-12A, IL-1β) anti-inflammatory (IL-10, TGF-β1) cytokine expression hBM-MSC observed only culture (TNF IL-1β 10-fold, 0.001; TGF-β1 4-fold, 0.01 Day 16) confirming cells’ immunomodulatory mainly relation their not environment. This study supports use scaffolds, equipped growth factor controlled delivery, tissue engineered models vitro differentiation opens clinical perspectives injectable collagen-based advanced therapy systems.