Small Intestinal Submucosa: A Tissue-Derived Extracellular Matrix That Promotes Tissue-Specific Growth and Differentiation of Cellsin Vitro

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Abstract
The importance of understanding cell–extracellular matrix (ECM) interaction is now evident as scientists, engineers, and physicians search for novel scaffolds that support and maintain tissue-specific cellular growth and function both in vivo and in vitro. Small intestinal submucosa (SIS) represents an ECM that has been derived from porcine intestine while preserving its natural composition and architecture. More recently, an extract of this physiologic ECM, which forms a three-dimensional gel in vitro, has been developed. When compared to routinely used culture substrata (e.g., plastic, Vitrogen, and Matrigel), intact SIS and SIS-derived gel possess unique compositional and architectural features. Simple squamous epithelial (pulmonary artery), fibroblastic (Swiss 3T3), glandular epithelial (adenocarcinoma), and smooth muscle-like (urinary bladder) cells were seeded upon intact SIS and SIS-derived gel and their morphologic response evaluated. For each of the four cell types studied, intact SIS and SIS-derived gel were equivalent or superior in their ability to support and maintain expression of tissue-specific phenotype when compared to the routinely used substrata, plastic, Vitrogen, and Matrigel. Therefore, SIS may provide a novel biologically derived scaffold for the growth and study of a variety of cell types in vitro. Such information regarding the influence of substrate structure and function on cell behavior will be useful in the development of successful tissue engineering strategies.