Principles of Tissue Engineering and Reconstruction Using Polymer-Cell Constructs
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PRINCIPLES OF TISSUE ENGINEERING AND RECONSTRUCTION USING POLYMER-CELL CONSTRUCTS David J. Mooney, Linda Cima, and Robert Langer, Dept. of Chemical Engineering, MIT, Cambridge, MA, 02139 Lynt Johnson, Linda K. Hansen, Donald E. Ingber, and Joseph P. Vacanti, Depts. of Surgical Research and Pathology, Children's Hospital and Harvard Medical School, Boston, MA, 02115 ABSTRACT The fields of materials science, cell and molecular biology, and surgical reconstruction are merging to create new devices for surgical transplantation and reconstructive applications. The field of artificial devices for implantation has matured over the last 40 years. Likewise, the field of transplantation and tissue reconstruction has undergone enormous change and improvements over the last 30 years. It has been proposed that these fields merge to create new tissue substitutes for functional replacement, therapy or reconstructive applications. Over the last five years, our lab has experimented with the concept of using man-made, biodegradable polymer systems as scaffolding for cell implantation devices. They have been designed to maximize diffusion parameters allowing nutrient exchange, gas exchange, and waste exchange. Vascular ingrowth occurs in the implant with This leaves a permanently subsequent resorption of the original polymer. engrafted new tissue which is a chimera of donor cells for functional replacement and recipient mesenchymal elements including blood vessels and supporting tissue. We have experimented in several model systems including hepatocyte implants, chondrocyte implants for cartilage reconstruction, urethelial implants for urinary reconstruction, and more recently small bowel and bone. Across this broad front of tissue types, much new knowledge has been gained and there continues to be hope that this will achieve clinical application. INTRODUCTION The fields of organ transplantation and tissue reconstruction suffer from three major problems 1) a scarcity of donor or reconstructive tissue, 2) a high cost, and 3) problems associated with tissue rejection or side-effects of the immunosuppresion used to reduce tissue rejection. In 1989, for example, 30,000 deaths resulted from liver disease but only 2160 transplants were performed (1). Many of these deaths could have been avoided if a sufficient number of donor organs were available. One possible solution to these problems is to engineer new tissue by transplanting selected cell populations If functional tissue can be reconstructed using cell transplantation it (2). may alleviate the problem of donor tissue scarcity as the cells from one organ could be used for several recipients, and/or the available cells may be multiplied in vitro before implantation, potentially creating an endless supply of transplantable tissue. Additionally, the cost of isolating the cells and subsequently introducing them to the recipient may be much less than whole In applications such as bone or cartilage replacement organ transplantation. it may also eventually be possible to isolate cells from a
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