Chitosan-based Scaffold Counteracts Hypertrophic and Fibrotic Markers in Chondrogenic Differentiated Mesenchymal Stromal Cells

Cristina Manferdini, Elena Gabusi, Luciana Sartore, Kamol Dey, Silvia Agnelli, Camillo Almici, Andrea Bianchetti, Nicoletta Zini, Domenico Russo, Federica Re, Erminia Mariani, Gina Lisignoli

Research output: Contribution to journalArticle

Abstract

Cartilage tissue engineering remains problematic since no systems are able to induce signals that contribute to native cartilage structure formation. Therefore, we tested the potentiality of gelatin-polyethylene glycol scaffolds containing three different concentrations of chitosan (CH) (0%, 8% and 16%) on chondrogenic differentiation of human platelet lysate (HPL)-expanded human bone marrow mesenchymal stromal cells (hBM-MSCs). Typical chondrogenic (SOX9, collagen type 2 and aggrecan), hypertrophic (collagen type 10) and fibrotic (collagen type 1) markers were evaluated at gene and protein level at day 1, 28 and 48. We demonstrated that 16% CH scaffold had the highest percentage of relaxation with the fastest relaxation rate. In particular, 16% CH scaffold, combined with chondrogenic factor TGFβ3, was more efficient in inducing hBM-MSCs chondrogenic differentiation compared to 0% or 8% scaffolds. Collagen type 2, SOX9 and aggrecan showed the same expression in all scaffolds, while collagen type 10 and collagen type 1 markers were efficiently down-modulated only in 16% CH. We demonstrated that using HPL chronically during hBM-MSCs chondrogenic differentiation, the chondrogenic, hypertrophic and fibrotic markers were significantly decreased. Our data demonstrate that only a high concentration of CH, combined with TGFβ3, creates an environment capable of guiding in vitro hBM-MSCs towards a phenotypically stable chondrogenesis.

Original languageEnglish
Pages (from-to)1896-1911
Number of pages16
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume13
Issue number10
Early online dateJul 26 2019
DOIs
Publication statusPublished - Oct 2019

    Fingerprint

Keywords

  • chitosan scaffold
  • chondrogenic differentiation
  • fibrotic markers
  • human platelet lysate
  • hypertrophic markers
  • mesenchymal stromal cells
  • stress relaxation

Cite this