An overview of the pathology and approaches to tissue engineering

Abstract

In tissue engineering, there is an attempt to culture living tissues for surgical transplantation. In vitro and in vivo approaches have produced vascular and cardiovascular components, cartilage, bone, intestine, and liver. Attempts to microdesign cell-culture support scaffolds have used a new generation of biocompatible and bioabsorbable polymers. Suspensions of donor cells are seeded onto protein-coated polymer scaffolds and grown to confluence in dynamic bioreactors. In vitro techniques produce monolayers of tissues. Denser masses are achieved by implanting monolayers onto a host, or by culturing cell/polymer constructs in vivo. Existing techniques have produced functioning heart valves from sheep endothelial cells and myofibroblasts. Cultured ovine arterial cells have replaced 2-cm segments of pulmonary artery in lambs. Chondrocyte cultures have produced a human-ear-shaped construct, temporo-mandibular joint discs, meniscal replacement devices, and human-phalange-shaped constructs, complete with a joint. The culture of composite tissue types has recently been reported. Intestinal organoid units containing a mesenchymal core with surrounding polarized epithelia have been used in lieu of an ileal pouch in Lewis rats, and the long-term culture of rat hepatocytes has revealed cellular differentiation and neomorphology resembling elements of a biliary drainage system. To sustain the in vitro culture of dense tissues prior to implantation, micro-electro-mechanical systems (MEMS) fabrication technologies have been adapted to create wafers of polymer containing sealed, branching, vascular-type spaces. After seeding with rat lung endothelial cells, followed by 5 days of bioreactor culture, the result is an endothelial network with controlled blood flow rates, pressure, and hematocrit. When these customized vascular systems can be used to support in vitro culture, a new generation of dense, composite, morphologically complex tissues will be available for clinical development.