3D Biomimetic Scaffold for Growth Factor Controlled Delivery: An In-Vitro Study of Tenogenic Events on Wharton's Jelly Mesenchymal Stem Cells.

Camilla Ciardulli, Maria; Lovecchio, Joseph; Scala, Pasqualina; Pavel Lamparelli, Erwin; Dale, Tina; Giudice, Valentina; Giordano, Emanuele; Selleri, Carmine; Robert Forsyth, Nicholas; Maffulli, Nicola; Della Porta, Giovanna

doi:10.3390/pharmaceutics13091448

3D Biomimetic Scaffold for Growth Factor Controlled Delivery: An In-Vitro Study of Tenogenic Events on Wharton's Jelly Mesenchymal Stem Cells.

Camilla Ciardulli, Maria; Lovecchio, Joseph; Scala, Pasqualina; Pavel Lamparelli, Erwin; Dale, Tina; Giudice, Valentina; Giordano, Emanuele; Selleri, Carmine; Robert Forsyth, Nicholas; Maffulli, Nicola; Della Porta, Giovanna

Authors

Maria Camilla Ciardulli

Joseph Lovecchio

Pasqualina Scala

Erwin Pavel Lamparelli

Tina Dale t.p.dale@keele.ac.uk

Valentina Giudice

Emanuele Giordano

Carmine Selleri

Nicholas Robert Forsyth

Nicola Maffulli

Giovanna Della Porta

Abstract

The present work described a bio-functionalized 3D fibrous construct, as an interactive teno-inductive graft model to study tenogenic potential events of human mesenchymal stem cells collected from Wharton's Jelly (hWJ-MSCs). The 3D-biomimetic and bioresorbable scaffold was functionalized with nanocarriers for the local controlled delivery of a teno-inductive factor, i.e., the human Growth Differentiation factor 5 (hGDF-5). Significant results in terms of gene expression were obtained. Namely, the up-regulation of Scleraxis (350-fold, p = 0.05), type I Collagen (8-fold), Decorin (2.5-fold), and Tenascin-C (1.3-fold) was detected at day 14; on the other hand, when hGDF-5 was supplemented in the external medium only (in absence of nanocarriers), a limited effect on gene expression was evident. Teno-inductive environment also induced pro-inflammatory, (IL-6 (1.6-fold), TNF (45-fold, p = 0.001), and IL-12A (1.4-fold)), and anti-inflammatory (IL-10 (120-fold) and TGF-ß1 (1.8-fold)) cytokine expression upregulation at day 14. The presented 3D construct opens perspectives for the study of drug controlled delivery devices to promote teno-regenerative events.

Journal Article Type	Article
Acceptance Date	Sep 8, 2021
Publication Date	Sep 10, 2021
Journal	Pharmaceutics
Publisher	MDPI
Peer Reviewed	Peer Reviewed
Volume	13
Issue	9
DOI	https://doi.org/10.3390/pharmaceutics13091448
Keywords	human Wharton's Jelly Mesenchymal Stem Cells; hGDF-5 controlled delivery; PLGA nanocarriers; 3D fibrin scaffold; tenogenic commitment; cyclic strain bioreactor systems
Publisher URL	https://doi.org/10.3390/pharmaceutics13091448