Tissue Engineering: An Overview
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other metals as the preferred orthopedic implant materials. The explosive growth of the polymer industry following World War II led to the discovery of numerous new materials with exciting properties. Initially the search for polymeric biomaterials was restricted to stable polymers (such as Dacron, Teflon, or Silastic), which were regarded as "biologically inert" at that time. During the 1980s, it was recognized that biological inertness may not always be a desirable property since interactions between the implant and the surrounding tissue can be exploited to the benefit of the patient. At that time, dramatic advances in our ability to design new, degradable polymers, combined with a thorough understanding of immunology and cell biology, provided for the first time the scientific foundation for the rational design of tissue substitutes. Only eight years after the first workshop on tissue engineering in 1988, tissue engineering is now coming to the forefront as a cutting-edge scientific discipline with dramatic scientific, societal, and commercial potential. Three main challenges need to be addressed before the vision of ample supplies of engineered artificial-tissue substitutes will become a clinical reality: (1) The materials base of the medicaldevice industry needs to be enriched with new materials that are fully bioresorbable. At this point, poly(glycolic acid) (PGA), poly(lactic acid) (PLA), polydioxanone, and copolymers thereof are the only synthetic, degradable polymers with an extensive Food and Drug Administration approval history. Although the utility of these materials as sutures and in a number of drug-delivery applications is well-established, a wide range of material needs cannot be addressed by the use of only these polyesters. (2) New processing techniques are required that will provide reproducible patterns and three-dimensional architectures at the micrometer and possibly the nanometer scale. Polymers in the ex-
tracellular matrix have evolved to contain chemical sequences and patterns that provide signals crucial to normal cell function. Currently available synthetic implant materials, lacking these natural messages, often trigger aberrant cell responses. Only through the development of improved processing techniques will it be possible to control the effects of patterns and three-dimensional architecture on the biological response of diverse cell types and tissues. (3) A comprehensive understanding of the parameters that control the cellmaterial interaction is needed to provide optimum conditions for the attachment, growth, differentiation, and threedimensional organization of individual cells into viable tissues. This requires the interdisciplinary blending of the materials sciences with cell and molecular biology and represents the most fundamental and most difficult of all three challenges. With progress in these areas, it will be possible to manufacture materials that will actively support the attachment and growth of specific cell types and that will provide a "scaffold" for the threed
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