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INTRODUCTION

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Tissue engineering is a field that applies principles of regenerative medicine to restore the function of various organs by combining cells with biomaterials. It is multidisciplinary, often combining the skills of physicians, cell biologists, bioengineers, and material scientists, to recapitulate the native three-dimensional architecture of an organ, the appropriate cell types, and the supportive nutrients and growth factors that allow normal cell growth, differentiation, and function. Tissue engineering is a relatively new field, originating in the late 1970s. Early studies focused on efforts to create skin substitutes using biomaterials and epithelial skin cells with a goal of providing barrier protection for patients with burns. The early strategies employed a tissue biopsy, followed by ex vivo expansion of cells seeded on scaffolds. The cell–scaffold composite was later implanted back into the same patient, where the new tissue would mature. However, there were many hurdles to overcome. The three major challenges in the field of tissue engineering involved: (1) the ability to grow and expand normal primary human cells in large quantities; (2) the identification of appropriate biomaterials; and (3) the requirement for adequate vascularization and innervation of the engineered constructs.

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ISOLATION AND GROWTH OF CELLS

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The original model for tissue engineering focused largely on the isolation of tissue from the organ of interest, the growth and expansion of the tissue-specific cells, and the seeding of these cells onto three-dimensional scaffolds. Just a few decades ago, most primary cultures of human cells could not be grown and expanded in large quantities, representing a major impediment to the engineering of human tissues. However, the identification of specific tissue progenitor cells in the 1990s allowed expansion of multiple cell types, and progress has occurred steadily since then. Some cell types are more amenable to expansion than others, reflecting in part their native regenerative capacity but also varying requirements for nutrients, growth factors, and cell–cell contacts. As an example of progress, after years of effort, protocols for the growth and expansion of human cardiomyocytes are now available. However, there are still many tissue-specific cell types that cannot be expanded from tissue sources, including the pancreas, liver, and nerves. The discovery of pluripotent or highly multipotent stem cells (Chap. 88) may ultimately allow most human cell types to be used for tissue engineering. The stem cell characteristics depend on their origin and their degree of plasticity, with cells from the earliest developmental stages, such as embryonic stem cells, having the greatest plasticity. Induced pluripotent stem cells have the advantage that they can be derived from individual patients, allowing autologous transplants. They can also be differentiated, in vitro, along cell-specific lineages, although these protocols are still at an early stage of development. Human embryonic and induced pluripotent stem cells have a very high replicative potential, but they also have the potential for rejection and tumor formation (e.g., teratomas). The more recently described amniotic fluid and placental stem cells have a ...

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