Growth factors for sequential cellular de- and re-differentiation in tissue engineering |
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Authors: | Pei M Seidel J Vunjak-Novakovic G Freed L E |
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Institution: | Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139-4307, USA |
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Abstract: | A model system for the in vitro generation of cartilaginous constructs was used to study a tissue engineering paradigm whereby sequentially applied growth factors promoted chondrocytes to first de-differentiate into a proliferative state and then re-differentiate and undergo chondrogenesis. Early cultivation in medium with supplemental TGF-β1/FGF-2 doubled cell fractions in 2-week constructs compared to unsupplemented controls. Subsequent culture with supplemental IGF-I yielded large 4-week constructs with high fractions of cartilaginous extracellular matrix (ECM) and high compressive moduli, whereas prolonged culture with supplemental FGF-2 yielded small 4-week constructs with low ECM fractions and moduli. Sequential supplementation with TGF-β1/FGF-2 and then IGF-I yielded 4-week constructs with type-specific mRNA expression and protein levels that were high for type II and negligible for type I collagen, in contrast to other growth factor regimens studied. The data demonstrate that structural, functional, and molecular properties of engineered cartilage can be modulated by sequential application of growth factors. |
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Keywords: | Tissue engineering Chondrocyte Biomaterial Bioreactor TGF-β1 FGF-2 IGF-I |
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