scholarly journals Tendon and Cytokine Marker Expression by Human Bone Marrow Mesenchymal Stem Cells in a Hyaluronate/Poly-Lactic-Co-Glycolic Acid (PLGA)/Fibrin Three-Dimensional (3D) Scaffold

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1268 ◽  
Author(s):  
Maria C. Ciardulli ◽  
Luigi Marino ◽  
Joseph Lovecchio ◽  
Emanuele Giordano ◽  
Nicholas R. Forsyth ◽  
...  

We developed a (three-dimensional) 3D scaffold, we named HY-FIB, incorporating a force-transmission band of braided hyaluronate embedded in a cell localizing fibrin hydrogel and poly-lactic-co-glycolic acid (PLGA) nanocarriers as transient components for growth factor controlled delivery. The tenogenic supporting capacity of HY-FIB on human-Bone Marrow Mesenchymal Stem Cells (hBM-MSCs) was explored under static conditions and under bioreactor-induced cyclic strain conditions. HY-FIB elasticity enabled to deliver a mean shear stress of 0.09 Pa for 4 h/day. Tendon and cytokine marker expression by hBM-MSCs were studied. Results: hBM-MSCs embedded in HY-FIB and subjected to mechanical stimulation, resulted in a typical tenogenic phenotype, as indicated by type 1 Collagen fiber immunofluorescence. RT-qPCR showed an increase of type 1 Collagen, scleraxis, and decorin gene expression (3-fold, 1600-fold, and 3-fold, respectively, at day 11) in dynamic conditions. Cells also showed pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokine gene expressions, with a significant increase of anti-inflammatory cytokines in dynamic conditions (IL-10 and TGF-β1 300-fold and 4-fold, respectively, at day 11). Mechanical signaling, conveyed by HY-FIB to hBM-MSCs, promoted tenogenic gene markers expression and a pro-repair cytokine balance. The results provide strong evidence in support of the HY-FIB system and its interaction with cells and its potential for use as a predictive in vitro model.

2015 ◽  
Vol 77 (25) ◽  
Author(s):  
Rozlin Abdul Rahman ◽  
Norhamiza Mohamad Sukri ◽  
Noorhidayah Md Nazir ◽  
Muhammad Aa’zamuddin Ahmad Radzi ◽  
Ahmad Hafiz Zulkifly ◽  
...  

Articular cartilage has poor repair capacity due to its avascular and aneural properties and has relatively few cells. This study investigated the ability of autologous implantation approach using three dimensional (3D) constructs engineered from bone marrow mesenchymal stem cells (BMSCs) seeded on poly(lactic-co-glycolic acid) (PLGA) with or without fibrin as cells carrier for the repair of osteochondral defect in rabbit model. The engineered 3D constructs – PLGA/Fibrin/BMSCs and PLGA/BMSCs – were cultured for 3 weeks in vitro and implanted autologously to the osteochondral defect created in the rabbit knee. The in vivo constructs were harvested and evaluated by means of gross observation, histology assessment, gene expression study, sulphated glycosaminoglycan (sGAG) production assay and biomechanical evaluation at 6 and 12 weeks post implantation. The results showed that the osteochondral defects treated with the PLGA/Fibrin/BMSCs constructs exhibited better repairment, more cartilaginous extracellular matrix, higher sGAG production, superior compressive strength and more intense expression of chondrogenic marker genes than the PLGA/BMSCs group. This study suggested that the PLGA/Fibrin/BMSCs has the potential to treat osteochondral defect and may be presented as a viable therapeutic option for those who would be in need from the life-extending benefits of tissue replacement or repair.


2005 ◽  
Vol 47 (1-3) ◽  
pp. 11-17 ◽  
Author(s):  
Chikayoshi Matsuda ◽  
Mutsumi Takagi ◽  
Takako Hattori ◽  
Shigeyuki Wakitani ◽  
Toshiomi Yoshida

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 399
Author(s):  
Erwin Pavel Lamparelli ◽  
Joseph Lovecchio ◽  
Maria Camilla Ciardulli ◽  
Valentina Giudice ◽  
Tina P. Dale ◽  
...  

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.


Sign in / Sign up

Export Citation Format

Share Document