Ultrasound Stimulation of Piezoelectric Nanocomposite Hydrogels Boosts Chondrogenic Differentiation in Vitro, in Both a Normal and Inflammatory Milieu

The use of piezoelectric nanomaterials combined with ultrasound stimulation is emerging as a promising approach for wirelessly triggering the regeneration of different tissue types. However, it has never been explored for boosting chondrogenesis. Furthermore, the ultrasound stimulation parameters used are often not adequately controlled. In this study, we show that adipose-tissue-derived mesenchymal stromal cells embedded in a nanocomposite hydrogel containing piezoelectric barium titanate nanoparticles and graphene oxide nanoflakes and stimulated with ultrasound waves with precisely controlled parameters (1 MHz and 250 mW/cm2, for 5 min once every 2 days for 10 days) dramatically boost chondrogenic cell commitment in vitro. Moreover, fibrotic and catabolic factors are strongly down-modulated: proteomic analyses reveal that such stimulation influences biological processes involved in cytoskeleton and extracellular matrix organization, collagen fibril organization, and metabolic processes. The optimal stimulation regimen also has a considerable anti-inflammatory effect and keeps its ability to boost chondrogenesis in vitro, even in an inflammatory milieu. An analytical model to predict the voltage generated by piezoelectric nanoparticles invested by ultrasound waves is proposed, together with a computational tool that takes into consideration nanoparticle clustering within the cell vacuoles and predicts the electric field streamline distribution in the cell cytoplasm. The proposed nanocomposite hydrogel shows good injectability and adhesion to the cartilage tissue ex vivo, as well as excellent biocompatibility in vivo, according to ISO 10993. Future perspectives will involve preclinical testing of this paradigm for cartilage regeneration.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:18

Enthalten in:

ACS nano - 18(2024), 3 vom: 23. Jan., Seite 2047-2065

Sprache:

Englisch

Beteiligte Personen:

Ricotti, Leonardo [VerfasserIn]
Cafarelli, Andrea [VerfasserIn]
Manferdini, Cristina [VerfasserIn]
Trucco, Diego [VerfasserIn]
Vannozzi, Lorenzo [VerfasserIn]
Gabusi, Elena [VerfasserIn]
Fontana, Francesco [VerfasserIn]
Dolzani, Paolo [VerfasserIn]
Saleh, Yasmin [VerfasserIn]
Lenzi, Enrico [VerfasserIn]
Columbaro, Marta [VerfasserIn]
Piazzi, Manuela [VerfasserIn]
Bertacchini, Jessika [VerfasserIn]
Aliperta, Andrea [VerfasserIn]
Cain, Markys [VerfasserIn]
Gemmi, Mauro [VerfasserIn]
Parlanti, Paola [VerfasserIn]
Jost, Carsten [VerfasserIn]
Fedutik, Yirij [VerfasserIn]
Nessim, Gilbert Daniel [VerfasserIn]
Telkhozhayeva, Madina [VerfasserIn]
Teblum, Eti [VerfasserIn]
Dumont, Erik [VerfasserIn]
Delbaldo, Chiara [VerfasserIn]
Codispoti, Giorgia [VerfasserIn]
Martini, Lucia [VerfasserIn]
Tschon, Matilde [VerfasserIn]
Fini, Milena [VerfasserIn]
Lisignoli, Gina [VerfasserIn]

Links:

Volltext

Themen:

Chondrogenesis
Hydrogel
Hydrogels
Inflammation
Journal Article
Mesenchymal stromal cell
Nanogels
Nanomaterial
Piezoelectric
Ultrasound

Anmerkungen:

Date Completed 24.01.2024

Date Revised 28.01.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acsnano.3c08738

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM36656787X