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Volume 13
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Article

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

by
Erwin Pavel Lamparelli
1,
Joseph Lovecchio
2,3,
Maria Camilla Ciardulli
1,
Valentina Giudice
1,
Tina P. Dale
4,
Carmine Selleri
1,
Nicholas Forsyth
4,
Emanuele Giordano
2,3,5,
Nicola Maffulli
1 and
Giovanna Della Porta
1,6,*
1
Department of Medicine, Surgery and Dentistry, University of Salerno, via S. Allende, 84081 Baronissi, SA, Italy
2
Department of Electrical, Electronic and Information Engineering “Guglielmo Marconi” (DEI), University of Bologna, via dell’Università 50, 47522 Cesena, FC, Italy
3
Health Sciences and Technologies-Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, via Tolara di Sopra 41/E, 40064 Ozzano dell’Emilia, BO, Italy
4
Guy Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK
5
Advanced Research Center on Electronic Systems (ARCES), University of Bologna, via Vincenzo Toffano 2/2, 40125 Bologna, BO, Italy
6
Research Centre for Biomaterials BIONAM, Università di Salerno, via Giovanni Paolo II, 84084 Fisciano, SA, Italy
*
Author to whom correspondence should be addressed.
Pharmaceutics 2021, 13(3), 399; https://doi.org/10.3390/pharmaceutics13030399
Submission received: 8 February 2021 / Revised: 11 March 2021 / Accepted: 13 March 2021 / Published: 17 March 2021
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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Abstract

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

Lamparelli, E.P.; Lovecchio, J.; Ciardulli, M.C.; Giudice, V.; Dale, T.P.; Selleri, C.; Forsyth, N.; Giordano, E.; Maffulli, N.; Della Porta, G. Chondrogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells in a Perfused Collagen Hydrogel Functionalized with hTGF-β1-Releasing PLGA Microcarrier. Pharmaceutics 2021, 13, 399. https://doi.org/10.3390/pharmaceutics13030399

AMA Style

Lamparelli EP, Lovecchio J, Ciardulli MC, Giudice V, Dale TP, Selleri C, Forsyth N, Giordano E, Maffulli N, Della Porta G. Chondrogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells in a Perfused Collagen Hydrogel Functionalized with hTGF-β1-Releasing PLGA Microcarrier. Pharmaceutics. 2021; 13(3):399. https://doi.org/10.3390/pharmaceutics13030399

Chicago/Turabian Style

Lamparelli, Erwin Pavel, Joseph Lovecchio, Maria Camilla Ciardulli, Valentina Giudice, Tina P. Dale, Carmine Selleri, Nicholas Forsyth, Emanuele Giordano, Nicola Maffulli, and Giovanna Della Porta. 2021. "Chondrogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells in a Perfused Collagen Hydrogel Functionalized with hTGF-β1-Releasing PLGA Microcarrier" Pharmaceutics 13, no. 3: 399. https://doi.org/10.3390/pharmaceutics13030399

APA Style

Lamparelli, E. P., Lovecchio, J., Ciardulli, M. C., Giudice, V., Dale, T. P., Selleri, C., Forsyth, N., Giordano, E., Maffulli, N., & Della Porta, G. (2021). Chondrogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells in a Perfused Collagen Hydrogel Functionalized with hTGF-β1-Releasing PLGA Microcarrier. Pharmaceutics, 13(3), 399. https://doi.org/10.3390/pharmaceutics13030399

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