Tissue engineering

Tissue engineering holds promise for an entirely new approach to the repair and reconstruction of tissues and organs damaged by disease, injury, or genetic abnormalities. A promising therapeutic modality, gene therapy is broadly defined as the transfer of genes to cells or tissues for a therapeutic effect. Stelios Andreadis, assistant professor of chemical engineering and codirector of the Center for Biomedical Engineering, and his team are working to impart new functions to cells or enhance existing cellular activities in order to improve the therapeutic potential of skin substitutes, thus aiding burn victims or otherwise-injured individuals. Recent work in his laboratory has important implications for gene transfer to epidermal stem cells and they may also find wider applicability to stem cells of other tissues.

The team also prepares and uses three-dimensional skin equivalents as model systems to study tissue development and wound-healing. When engineered skin is transplanted onto mice that lack an active immune system, it integrates with the mouse skin. The transplanted tissues are then wounded to study wound-healing of human skin in vivo. Andreadis’s group employs the technology of cDNA arrays to monitor the levels of gene expression during epidermopoiesis in vitro and in vivo. Specifically, cDNA arrays are used to study the response of engineered skin to barrier disruption and the protective effects of keratinocyte growth factor. This study revealed very interesting molecular information regarding the response of engineered tissue to injury and allowed the development of novel hypotheses to understand how complex molecular interactions lead to a certain tissue phenotype. Functional genomics is employed to obtain the molecular fingerprint of engineered tissues before application in the clinic or as cell biosensors.

Recently, Andreadis, James Russell, and Daniel Swartz have constructed engineered small-diameter blood vessels, with smooth muscle cells embedded in fibrin gels. The tissue-engineered vessels exhibit considerable mechanical strength and reactivity to multiple constrictors and dilators after only two weeks in culture. These tissues can be used as a biological model to address questions relating to vessel development, disease progression and as a toxicological model for drug testing, significantly impacting the treatment of cardiovascular disease.