The regulation of expanded human nasal chondrocyte re-differentiation capacity by substrate composition and gas plasma surface modification

T.B.F. Woodfield, Sylvie Miot, Ivan Martin, Clemens van Blitterswijk, J.U. Riesle

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Abstract

Optimizing re-differentiation of clinically relevant cell sources on biomaterial substrates in serum containing (S+) and serum-free (SF) media is a key consideration in scaffold-based articular cartilage repair strategies. We investigated whether the adhesion and post-expansion re-differentiation of human chondrocytes could be regulated by controlled changes in substrate surface chemistry and composition in S+ and SF media following gas plasma (GP) treatment. Expanded human nasal chondrocytes were plated on gas plasma treated (GP+) or untreated (GP−) poly(ethylene glycol)-terephthalate–poly(butylene terephthalate) (PEGT/PBT) block co-polymer films with two compositions (low or high PEG content). Total cellularity, cell morphology and immunofluorescent staining of vitronectin (VN) and fibronectin (FN) integrin receptors were evaluated, while post-expansion chondrogenic phenotype was assessed by collagen types I and II mRNA expression. We observed a direct relationship between cellularity, cell morphology and re-differentiation potential. Substrates supporting high cell adhesion and a spread morphology (i.e. GP+ and low PEG content films), resulted in a significantly greater number of cells expressing α5β1 FN to αVβ3 VN integrin receptors, concomitant with reduced collagen type II/I mRNA gene expression. Substrates supporting low cell adhesion and a spherical morphology (GP− and high PEG content films) promoted chondrocyte re-differentiation indicated by high collagen type II/I gene expression and a low percentage of α5β1 FN integrin expressing cells. This study demonstrates that cell–substrate interactions via α5β1 FN integrin mediated receptors negatively impacts expanded human nasal chondrocyte re-differentiation capacity. GP treatment promotes cell adhesion in S+ media but reverses the ability of low PEG content PEGT/PBT substrates to maintain chondrocyte phenotype. We suggest alternative cell immobilization techniques to GP are necessary for clinical application in articular cartilage repair.
Original languageUndefined
Pages (from-to)1043-1053
JournalBiomaterials
Volume27
Issue number7
DOIs
Publication statusPublished - 2006

Keywords

  • Chondrocyte
  • Surface modification
  • Fibronectin
  • Cartilage tissue engineering
  • Vitronectin
  • IR-67206
  • METIS-229770
  • Gene expression
  • PCR

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