Assessing the functional potential of conditioned media derived from amniotic epithelial stem cells engineered on 3D biomimetic scaffolds : An in vitro model for tendon regeneration

© 2024 The Authors..

Tendon diseases pose a significant challenge in regenerative medicine due to the limited healing capacity of this tissue. Successful tendon regeneration requires a combination of angiogenesis, immune response, and tenogenesis processes. An effective tendon engineering (TE) strategy must finely tune this systems' interplay toward homeostasis. This study explores in vitro the paracrine influence of amniotic epithelial stem cells (AECs) engineered on a validated 3D electrospun PLGA scaffolds on HUVECs (angiogenesis), PBMCs/Jurkat (immune response), and AECs (tenogenic stem cell activation). The results revealed the role of scaffold's topology and topography in significantly modulating the paracrine profile of the cells. In detail, AECs basal release of bioactive molecules was boosted in the cells engineered on 3D scaffolds, in particular VEGF-D, b-FGF, RANTES, and PDGF-BB (p < 0.0001 vs. CMCTR). Moreover, biological tests demonstrated 3D scaffolds' proactive role in potentiating AECs' paracrine inhibition on PBMCs proliferation (CM3Dvs. CTR, p < 0.001) and LPS-mediated Jurkat activation with respect to controls (CM3D and CM2Dvs. CTR, p < 0.01 and p < 0.05, respectively), without exerting any in vitro pro-angiogenic role in promoting HUVECs proliferation and tubule formation. Teno-inductive paracrine ability of AECs engineered on 3D scaffolds was assessed on co-cultured ones, which formed tendon-like structures. These latter demonstrated an upregulation of tendon-related genes (SCX, THBS4, COL1, and TNMD) and the expression TNMD and COL1 proteins. Overall, this research underscores the pivotal role of the 3D topology and topography of PLGA tendon mimetic scaffolds in orchestrating effective tendon regeneration through modulating cell behavior and crosstalk between engineered stem cells and different subpopulations in the damaged tendon.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

Materials today. Bio - 25(2024) vom: 27. März, Seite 101001

Sprache:

Englisch

Beteiligte Personen:

Russo, Valentina [VerfasserIn]
Prencipe, Giuseppe [VerfasserIn]
Mauro, Annunziata [VerfasserIn]
El Khatib, Mohammad [VerfasserIn]
Haidar-Montes, Arlette A [VerfasserIn]
Cambise, Nico [VerfasserIn]
Turriani, Maura [VerfasserIn]
Stöckl, Johannes [VerfasserIn]
Steinberger, Peter [VerfasserIn]
Lancia, Loreto [VerfasserIn]
Schnabelrauch, Matthias [VerfasserIn]
Berardinelli, Paolo [VerfasserIn]
Barboni, Barbara [VerfasserIn]

Links:

Volltext

Themen:

3D electrospun PLGA scaffolds
Amniotic epithelial stem cells (AECs)
Immunomodulation
Journal Article
Paracrine effect
Tenogenic differentiation

Anmerkungen:

Date Revised 01.03.2024

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.1016/j.mtbio.2024.101001

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369100654