Tendon Biomimetic Electrospun PLGA Fleeces Induce an Early Epithelial-Mesenchymal Transition and Tenogenic Differentiation on Amniotic Epithelial Stem Cells
Valentina Russo,
Mohammad El Khatib,
Lisa di Marcantonio,
Massimo Ancora,
Ralf Wyrwa,
Annunziata Mauro,
Torsten Walter,
Jürgen Weisser,
Maria Rita Citeroni,
Francesco Lazzaro,
Marta Di Federico,
Paolo Berardinelli,
Cesare Cammà,
Matthias Schnabelrauch,
Barbara Barboni
Affiliations
Valentina Russo
Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy
Mohammad El Khatib
Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy
Lisa di Marcantonio
Laboratory of Bacteriology, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “Giuseppe Caporale”, 64100 Teramo, Italy
Massimo Ancora
Laboratory of Molecular Biology and Genomic, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “Giuseppe Caporale, 64100 Teramo, Italy
Ralf Wyrwa
Department of Biomaterials, INNOVENT e. V, J-07749 Jena, Germany
Annunziata Mauro
Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy
Torsten Walter
Department of Biomaterials, INNOVENT e. V, J-07749 Jena, Germany
Jürgen Weisser
Department of Biomaterials, INNOVENT e. V, J-07749 Jena, Germany
Maria Rita Citeroni
Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy
Francesco Lazzaro
Research & Development Department, Assut Europe S.p.A., Magliano dei Marsi, 67062 L’Aquila, Italy
Marta Di Federico
Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy
Paolo Berardinelli
Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy
Cesare Cammà
Laboratory of Molecular Biology and Genomic, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “Giuseppe Caporale, 64100 Teramo, Italy
Matthias Schnabelrauch
Department of Biomaterials, INNOVENT e. V, J-07749 Jena, Germany
Barbara Barboni
Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy
Background. The design of tendon biomimetic electrospun fleece with Amniotic Epithelial Stem Cells (AECs) that have shown a high tenogenic attitude may represent an alternative strategy to overcome the unsatisfactory results of conventional treatments in tendon regeneration. Methods. In this study, we evaluated AEC-engineered electrospun poly(lactide-co-glycolide) (PLGA) fleeces with highly aligned fibers (ha-PLGA) that mimic tendon extracellular matrix, their biocompatibility, and differentiation towards the tenogenic lineage. PLGA fleeces with randomly distributed fibers (rd-PLGA) were generated as control. Results. Optimal cell infiltration and biocompatibility with both PLGA fleeces were shown. However, only ha-PLGA fleeces committed AECs towards an Epithelial-Mesenchymal Transition (EMT) after 48 h culture, inducing their cellular elongation along the fibers’ axis and the upregulation of mesenchymal markers. AECs further differentiated towards tenogenic lineage as confirmed by the up-regulation of tendon-related genes and Collagen Type 1 (COL1) protein expression that, after 28 days culture, appeared extracellularly distributed along the direction of ha-PLGA fibers. Moreover, long-term co-cultures of AEC-ha-PLGA bio-hybrids with fetal tendon explants significantly accelerated of half time AEC tenogenic differentiation compared to ha-PLGA fleeces cultured only with AECs. Conclusions. The fabricated tendon biomimetic ha-PLGA fleeces induce AEC tenogenesis through an early EMT, providing a potential tendon substitute for tendon engineering research.
