Podium Presentation Biomaterials and Scaffolds

16.2.7 - Low-Intensity Pulsed Ultrasound Induces Chondrogenic Differentiation of Adipose-Stromal Cells in 3D Piezoelectric Hydrogels

Presentation Topic
Biomaterials and Scaffolds
Date
14.04.2022
Lecture Time
12:00 - 12:09
Room
Potsdam 3
Session Type
Free Papers
Speaker
  • C. Manferdini (Bologna, IT)
Authors
  • C. Manferdini (Bologna, IT)
  • E. Gabusi (Bologna, IT)
  • P. Dolzani (Bologna, IT)
  • Y. Saleh (Bologna, IT)
  • D. Trucco (Bologna, IT)
  • M. Columbaro (Bologna, IT)
  • L. Vannozzi (Pisa, IT)
  • A. Cafarelli (Pisa, IT)
  • L. Ricotti (Pisa, IT)
  • G. Lisignoli (Bologna, IT)
Disclosure
This work received funding from the European Union's Horizon 2020 research and innovation program, grant agreement No 814413, project ADMAIORA (AdvanceD nanocomposite MAterIals fOr in situ treatment and ultRAsound-mediated management of osteoarthritis).

Abstract

Purpose

A major challenge in cartilage tissue engineering (TE) is to develop scaffolds capable of providing an instructive biomimetic environment to effectively drive mesenchymal stromal cells (MSCs) differentiation. Hydrogels have emerged as promising biomaterials for this purpose, due to their biocompatibility and ability to mimic the tissue extracellular matrix. Recently, graphene oxide (GO) emerged as a promising nanomaterial for cartilage TE due to chondroinductive properties when embedded into polymeric formulations. It has been also shown that piezoelectric nanomaterials, like barium titanate (BaTiO3) nanoparticles, can be exploited as nanoscale transducers capable of inducing cell growth/differentiation. Ultrasound waves are an interesting tool to facilitate chondrogenesis. In particular, it has been demonstrated that low-intensity pulsed ultrasound (LIPUS) regulates the differentiation of ASCs.

The aim of this study was to investigate whether dose-controlled LIPUS is able to influence chondrogenic differentiation of ASCs embedded in a 3D piezoelectric hydrogel.

Methods and Materials

ASCs at 2*106 cells/mL were embedded in a 3D VitroGel RGD® hydrogel with or without nanoparticles (GO, 25 µg/ml, BaTiO3, 50 µg/ml) and subjected to LIPUS stimulation every 2 days, until day 10 of culture.

Hydrogels were cultured and chondrogenically differentiated for 2, 7, 10 and 28 days. At each time point cell viability, cytotoxicity, gene expression and immunohistochemistry (COL2, aggrecan, SOX9, and COL1) were evaluated.

Results

In both 3D hydrogels we evidenced that LIPUS treatment did not affect negatively the viability of the embedded cells. LIPUS boosted the chondrogenic differentiation of ASCs laden in 3D piezoelectric hydrogel: the chondrogenic genes and proteins markers (COL2,aggrecan and SOX9) were increased while the fibrotic marker COL1 was decreased compared to control samples (non piezoelectric hydrogels and piezoelectric hydrogels not stimulated with LIPUS).

Conclusion

These results suggest that the combination of LIPUS and 3D piezoelectric hydrogels push the differentiation of ASCs and represent a promising tool in the field of cartilage TE.

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