Thinking inside the box: keeping tissue-engineered constructs in vitro for use as preclinical models

Tissue engineers have made great strides toward the creation of living tissue replacements for a wide range of tissue types and applications, with eventual patient implantation as the primary goal. However, an alternate use of tissue-engineered constructs exists: as in vitro preclinical models for purposes such as drug screening and device testing. Tissue-engineered preclinical models have numerous potential advantages over existing models, including cultivation in three-dimensional geometries, decreased cost, increased reproducibility, precise control over cultivation conditions, and the incorporation of human cells. Over the past decade, a number of researchers have developed and used tissue-engineered constructs as preclinical models for testing pharmaceuticals, gene therapies, stents, and other technologies, with examples including blood vessels, skeletal muscle, bone, cartilage, skin, cardiac muscle, liver, cornea, reproductive tissues, adipose, small intestine, neural tissue, and kidney. The focus of this article is to review accomplishments toward the creation and use of tissue-engineered preclinical models of each of these different tissue types.