May 2, 2003

Phenotype modulation in vascular tissue engineering using biochemical and mechanical stimulation

Annals of Biomedical Engineering
Jan P Stegemann, Robert M Nerem

Abstract

Biochemical stimulation was applied in combination with cyclic mechanical strain to engineered vascular constructs made of isolated smooth muscle cells in a three-dimensional (3D) collagen type 1 matrix. Platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta) were added exogenously to the medium used to culture the constructs. Mechanical stimulation was applied using a bioreactor system that imparted a 10% circumferential strain at a frequency of 1 Hz. The parameters studied were gel compaction, cell proliferation, and expression of the contractile protein smooth muscle alpha-actin (SMA). Mechanical stimulation caused a characteristic increase in gel compaction and cell proliferation, relative to statically cultured controls. Stimulation with PDGF increased cell proliferation and decreased SMA expression in 3D gels, but inhibited the effects of mechanical stimulation and produced a more open matrix structure. TGF-beta strongly inhibited cell proliferation and increased SMA expression, especially in the presence of mechanical strain, and resulted in a dense matrix. These results show that cell phenotype can be modulated in engineered blood vessels by applying selected combinations of biochemical and ...Continue Reading

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Mentioned in this Paper

Muscle, Smooth, Vascular
Transforming Growth Factor beta
Stress, Mechanical
Isoactin
Blood Vessel
Myocytes, Smooth Muscle
Recombinant Transforming Growth Factor-Beta
Fermentors
Mechanotransduction, Cellular
Smooth Muscle

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