As medicine therapy advances, we can now realistically set goals for fully functional living replacement of nearly every diseased organ or tissue. In the past several decades, the limitations of nonliving mechanical solutions to organ and tissue dysfunction are now recognized and include dialysis, mechanical heart valves, metallic orthopedic implants, and nonresorbable hernia mesh. Tissue engineering has broad goals including organ development, the elimination of the waiting time for transplants such as the liver and kidney, the creation of living tissue replacements for soft tissue, bone, cartilage, fascia, and virtually every structure in the body.
The principal mechanical supporting structure of any engineered tissue is the scaffold. These three-dimensional constructs are often composed of several materials and support the living cells required to generate a functional tissue (Fig. 69-1). The mechanical properties of the scaffolds, such as strength and elasticity, must correspond to the mechanical properties of the target tissue. Moreover, cells respond to environmental cues such that the scaffold should mimic the target tissue to achieve the desired cell alignment and the three-dimensional arrangement of the cells.
Schematic of basic principles of tissue engineering. (From R Langer, J Vacanti: Science 260:1993; with permission.)
The ideal scaffold materials for engineered tissues are resorbable materials that break down over time. During resorption, the engineered tissue is remodeled by normal healing processes, leaving only living cellular tissue with natural supporting connective tissue. Many implants or organ assist devices are under development utilizing the principles of tissue engineering with nonresorbable materials. These technologies such as lung assist devices, liver assist devices, and even composite implants with resorbable and nonresorbable components for orthopedic and hernia repair represent an important step toward developing fully resorbable scaffolds for all tissues. Current research is focused on resorbable synthetic polymers (e.g., polyglycolic acid, resorbable polyurethanes, polyglycerol sebacic acid); naturally occurring polymers (e.g., collagens, fibrin); and minerals (e.g., calcium triphosphate). Scaffold materials can be supplemented with growth factors or other cytokines to improve cellular incorporation and differentiation. Other surface modifications including surface texturing and protein or antibody coatings may improve cellular adhesion and migration.
Decellularized connective tissue, or organs, represents a rapidly developing area of materials for engineered tissues. Decellularized hearts reseeded with myocardial cells have been demonstrated to function in vitro, and research is focused on expanding this approach to other organs such as the lung and liver as well as soft tissues using material such as decellularized dermis.
The cellular components of engineered tissues must achieve organ functionality (e.g., hepatocytes), maintain organ structure (e.g., fibroblasts and stromal cells), and deliver blood to the tissue (e.g., endothelial cells and pericytes). The three-dimensional arrangement of the cells is critical for proper function; therefore, coordination of scaffold design and cellular components is essential. Maintenance of appropriate cell-to-cell interactions and cell-to-extracellular matrix interactions ...