Tendon and Cytokine Marker Expression by Human Bone Marrow Mesenchymal Stem Cells in a Hyaluronate/Poly-Lactic-Co-Glycolic Acid (PLGA)/Fibrin Three-Dimensional (3D) Scaffold

We developed a (three-dimensional) 3D scaffold, we named HY-FIB, incorporating a force-transmission band of braided hyaluronate embedded in a cell localizing fibrin hydrogel and poly-lactic-co-glycolic acid (PLGA) nanocarriers as transient components for growth factor controlled delivery. The tenoge...

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Veröffentlicht in:Cells (Basel, Switzerland) Jg. 9; H. 5; S. 1268
Hauptverfasser: Ciardulli, Maria C., Marino, Luigi, Lovecchio, Joseph, Giordano, Emanuele, Forsyth, Nicholas R., Selleri, Carmine, Maffulli, Nicola, Porta, Giovanna Della
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland MDPI 20.05.2020
MDPI AG
Schlagworte:
3D microenvironment
Adult
Biomarkers - metabolism
Bioreactors
Cells, Cultured
Cellular Microenvironment
Collagen - metabolism
cyclic strain
cytokines
Cytokines - metabolism
Drug Carriers - chemistry
Fibrin - chemistry
Gene Expression Regulation
Growth Differentiation Factor 5 - metabolism
hBM-MSCs
Humans
Hyaluronic Acid - chemistry
Mesenchymal Stem Cells - metabolism
Nanoparticles - chemistry
PLGA carriers
Polylactic Acid-Polyglycolic Acid Copolymer - chemistry
Tendons - metabolism
tenogenic markers
Tissue Scaffolds - chemistry
3D microenvironment
PLGA carriers
hBM-MSCs
cytokines
tenogenic markers
bioreactor
cyclic strain
ISSN:2073-4409, 2073-4409
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Zusammenfassung:We developed a (three-dimensional) 3D scaffold, we named HY-FIB, incorporating a force-transmission band of braided hyaluronate embedded in a cell localizing fibrin hydrogel and poly-lactic-co-glycolic acid (PLGA) nanocarriers as transient components for growth factor controlled delivery. The tenogenic supporting capacity of HY-FIB on human-Bone Marrow Mesenchymal Stem Cells (hBM-MSCs) was explored under static conditions and under bioreactor-induced cyclic strain conditions. HY-FIB elasticity enabled to deliver a mean shear stress of 0.09 Pa for 4 h/day. Tendon and cytokine marker expression by hBM-MSCs were studied. Results: hBM-MSCs embedded in HY-FIB and subjected to mechanical stimulation, resulted in a typical tenogenic phenotype, as indicated by type 1 Collagen fiber immunofluorescence. RT-qPCR showed an increase of type 1 Collagen, scleraxis, and decorin gene expression (3-fold, 1600-fold, and 3-fold, respectively, at day 11) in dynamic conditions. Cells also showed pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokine gene expressions, with a significant increase of anti-inflammatory cytokines in dynamic conditions (IL-10 and TGF-β1 300-fold and 4-fold, respectively, at day 11). Mechanical signaling, conveyed by HY-FIB to hBM-MSCs, promoted tenogenic gene markers expression and a pro-repair cytokine balance. The results provide strong evidence in support of the HY-FIB system and its interaction with cells and its potential for use as a predictive in vitro model.
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ISSN:2073-4409
2073-4409
DOI:10.3390/cells9051268