Chondroitin sulfate immobilized on a biomimetic scaffold modulates inflammation while driving chondrogenesis

Bruna Corradetti, Francesca Taraballi, Silvia Minardi, Jeffrey Van Eps, Fernando Cabrera, Lewis W. Francis, Salvatore A. Gazze, Mauro Ferrari, Bradley K. Weiner, Ennio Tasciotti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Costs associated with degenerative inflammatory conditions of articular cartilage are exponentially increasing in the aging population, and evidence shows a strong clinical need for innovative therapies. Stem cell-based therapies represent a promising strategy for the treatment of innumerable diseases. Their regenerative potential is undeniable, and it has been widely exploited in many tissue-engineering approaches, especially for bone and cartilage repair. Their immune-modulatory capacities in particular make stemcell-based therapeutics an attractive option for treating inflammatory diseases.However, because of their great plasticity, mesenchymal stem cells (MSCs) are susceptible to different external factors. Biomaterials capable of concurrently providing physical support to cells while acting as synthetic extracellular matrix have been established as a valuable strategy in cartilage repair. Here we propose a chondroitin sulfate-based biomimetic scaffold that recapitulates the physicochemical features of the chondrogenic niche and retains MSC immunosuppressive potential in vitro, either in response to a proinflammatory cytokineor in thepresenceof stimulatedperipheralbloodmononuclear cells. Inboth cases, a significant increase in the production ofmolecules associated with immunosuppression (nitric oxide and prostaglandins), as well as in the expression of their inducible enzymes (iNos, Pges, Cox-2, and Tgf-b). When implanted subcutaneously in rats, our scaffold revealed a reduced infiltration of leukocytes at 24 hours, which correlated with a greater upregulation of genes involved in inflammatory cell apoptotic processes. In supportof its effectiveuse in tissue-engineeringapplications of cartilagerepair, thepotential of the proposed platform to drive chondrogenic and osteogenic differentiation of MSC was also proven.

Original languageEnglish (US)
Pages (from-to)670-682
Number of pages13
JournalStem Cells Translational Medicine
Volume5
Issue number5
DOIs
StatePublished - 2016

Keywords

  • Arthritis
  • Biomimetic scaffolds
  • Chondrogenic differentiation
  • Chondroitin sulfate
  • Immunosuppression
  • Mesenchymal stem cells
  • Tissue engineering

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Chondroitin sulfate immobilized on a biomimetic scaffold modulates inflammation while driving chondrogenesis'. Together they form a unique fingerprint.

Cite this