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

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

doi:10.3390/pharmaceutics13091448

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-β1 (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.

Highlights

This article is an open access articleTendon injuries generate pain, swelling, loss of function of the tendon itself and nearby structures, and instability
Cytotoxicity was evaluated on the 3D scaffold bioengineered with 1 × 106
We evaluated cytokine transcript expression in the optimal tenoinductive setting: nanocarriers for human Growth Differentiation factor 5 (hGDF-5) controlled release

Summary

Introduction

Tendon injuries generate pain, swelling, loss of function of the tendon itself and nearby structures, and instability. Surgical procedures are elected when traditional modalities fail. Even if these approaches lead to a relatively high rate of success, they distributed under the terms and conditions of the Creative Commons. Pharmaceutics 2021, 13, 1448 sometimes present limitations [1]. Tendon tissue poorly responds to current treatments, resulting in permanent changes of the native tendon structures (with scar tissue formation and fibrosis) and biomechanics. The inability of complete healing derives from the nature of the tendon itself. It is poorly cellularized and vascularized, and has a low metabolism [2,3]

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