Engineered smooth muscle tissues: Regulating cell phenotype with the scaffold

Culturing cells on three-dimensional, biodegradable scaffolds may create ti ssues suitable either for reconstructive surgery applications or as novel i n vitro model systems. In this study, we have tested the hypothesis that th e phenotype of smooth muscle cells (SMCs) in three-dimensional, engineered tissues is regulated by the chemistry of the scaffold material. Specificall y, we have directly compared cell growth and patterns of extracellular matr ix (ECM) (e.g., elastin and collagen) gene expression on two types of synth etic polymer scaffolds and type I collagen scaffolds. The growth rates of S MCs on the synthetic polymer scaffolds were significantly higher than on ty pe I collagen sponges. The rate of elastin production by SMCs on polyglycol ic acid (PGA) scaffolds was 3.5 +/- 1.1-fold higher than that on type I col lagen sponges on Day 11 of culture. In contrast, the collagen production ra te on type I collagen sponges was 3.3 +/- 1.1-fold higher than that on PGA scaffolds. This scaffold-dependent switching between elastin and collagen g ene expression was confirmed by Northern blot analysis. The finding that th e scaffold chemistry regulates the phenotype of SMCs independent of the sca ffold physical form was confirmed by culturing SMCs on two-dimensional film s of the scaffold materials. It is likely that cells adhere to these scaffo lds via different ligands, as the major protein adsorbed from the serum ont o synthetic polymers was vitronectin, whereas fibronectin and vitronectin w ere present at high density on type I collagen sponges. In summary, this st udy demonstrates that three-dimensional smooth muscle-like tissues can be c reated by culturing SMCs on three-dimensional scaffolds, and that the pheno type of the SMCs is strongly regulated by the scaffold chemistry, These eng ineered tissues provide novel, three-dimensional models to study cellular i nteraction with ECM in vitro. (C) 1999 Academic Press.