Electrospun PLGA Fiber Diameter and Alignment of Tendon Biomimetic Fleece Potentiate Tenogenic Differentiation and Immunomodulatory Function of Amniotic Epithelial Stem Cells

Cells

Matthias Schnabelrauch¹  Ralf Wyrwa¹  Martina Schweder²  Andrea Polci³  Massimo Ancora⁴  Cesare Cammà⁴  Francesco Lazzaro⁵  Barbara Barboni⁶  Annunziata Mauro⁶  Luca Valbonetti⁶  Miriam Di Mattia⁶  Valentina Russo⁶  Paolo Berardinelli⁶  Oriana Di Giacinto⁶  Mohammad El Khatib⁶ 

[1] Department of Biomaterials, INNOVENT e. V., 07745 Jena, Germany;Department of Surface Engineering, INNOVENT e. V., 07745 Jena, Germany;Laboratory of Diagnosis and surveillance of foreign diseases, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “Giuseppe Caporale, 64100 Teramo, Italy;Laboratory of Molecular Biology and Genomic, Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “Giuseppe Caporale, 64100 Teramo, Italy;Research & Development Department, Assut Europe S.p.A., Magliano dei Marsi, 67062 L’Aquila, Italy;Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy;

关键词: tendon;    amniotic epithelial stem cells;    fiber diameter size;    aligned fibers;    tendon tissue engineering;    PLGA;   

DOI  :  10.3390/cells9051207

来源: DOAJ

【 摘 要 】

Injured tendons are challenging in their regeneration; thus, tissue engineering represents a promising solution. This research tests the hypothesis that the response of amniotic epithelial stem cells (AECs) can be modulated by fiber diameter size of tendon biomimetic fleeces. Particularly, the effect of electrospun poly(lactide-co-glycolide) (PLGA) fleeces with highly aligned microfibers possessing two different diameter sizes (1.27 and 2.5 µm: ha1- and ha2-PLGA, respectively) was tested on the ability of AECs to differentiate towards the tenogenic lineage by analyzing tendon related markers (Collagen type I: COL1 protein and mRNA Scleraxis: SCX, Tenomodulin: TNMD and COL1 gene expressions) and to modulate their immunomodulatory properties by investigating the pro- (IL-6 and IL-12) and anti- (IL-4 and IL-10) inflammatory cytokines. It was observed that fiber alignment and not fiber size influenced cell morphology determining the morphological change of AECs from cuboidal to fusiform tenocyte-like shape. Instead, fleece mechanical properties, cell proliferation, tenogenic differentiation, and immunomodulation were regulated by changing the ha-PLGA microfiber diameter size. Specifically, higher DNA quantity and better penetration within the fleece were found on ha2-PLGA, while ha1-PLGA fleeces with small fiber diameter size had better mechanical features and were more effective on AECs trans-differentiation towards the tenogenic lineage by significantly translating more efficiently SCX into the downstream effector TNMD. Moreover, the fiber diameter of 1.27 µm induced higher expression of pro-regenerative, anti-inflammatory interleukins mRNA expression (IL-4 and IL-10) with favorable IL-12/IL-10 ratio with respect to the fiber diameter of 2.5 µm. The obtained results demonstrate that fiber diameter is a key factor to be considered when designing tendon biomimetic fleece for tissue repair and provide new insights into the importance of controlling matrix parameters in enhancing cell differentiation and immunomodulation either for the cells functionalized within or for the transplanted host tissue.

【 授权许可】

Unknown