538 R.M.Nerem One of the more promising areas of tissue engineering is in the development of bio- logical substitutes based on the encapsulation of cultured cells.One of the important areas for use of encapsulated cell technology is in the development of bioartificial or- gans,e.g.,an artificial pancreas(20).Pancreas transplants have failed to be useful because of immunological rejection.An alternative approach is the development of implantable insulin pumps;however,these are not without problems either.This has led to the interest in developing a bioartificial pancreas (12).Although there are sev- eral possible designs for a bioartificial pancreas,one involves the use of microencap- sulated islet cells (31).In such a device,the islet cells,which secrete insulin,are surrounded by a semi-permeable membrane.This membrane must be permeable to the transport of insulin so it can be passed into the blood stream.The cells also will need nutrients,oxygen,and other molecules necessary for the maintenance of met- abolic function.However,the membrane must,in addition,protect the islet cells from bacteria,lymphocytes,and other proteins responsible for immune rejection.Impor- tant in the design of a bioartificial pancreas is its ability to respond rapidly to changes in glucose level.Equally necessary is the long term survival of the islet cells and the secretion of the insulin.As part of this,it also is important that islet cell function not change with a buildup of hormones.Although,in most of these areas,microencap- sulated islet cells function quite well,one problem is that the insulin production rate is on the low side. There are other applications of encapsulated cell technology in tissue engineering. Cima et al.(11)have shown that both liver and cartilage cells can be transplanted suc- cessfully,at least in small animals,using cells which are encapsulated in a degrada- ble polymer substrate.Neurological deficits also can be treated by transplantation within the brain of polymer encapsulated cells which release the missing neurotrans- mitter,and Aebischer et al.(1)have investigated the ability of encapsulated dopamine secreting cells to reverse experimental Parkinson's disease.Finally a major tissue- engineering market,where encapsulated cell technology may have application,is in the development of blood substitutes,i.e.,an artificial blood (36).Current efforts are based on the chemical cross-linking of hemoglobin,in many cases bovine derived,but there are potential problems associated with both incomplete cross-linking and the in- troduction of the foreign,bovine proteins into the body.In the future the use of mi- croencapsulation,together with stem-cell culture and controlled hematopoiesis, should prove important. Another application of tissue engineering is in the development of an artificial blood vessel for use in the bypass and replacement of diseased arteries (24,42).A number of groups have been interested in applying cell culture technology to the de- velopment of such tissue-engineered vascular prostheses.Much of this effort has been focused on hybrid vascular grafts,i.e.,a graft constructed out of synthetic material such as dacron or polytetrafluoroethylene(PTFE),but seeded with cultured endothe- lial cells prior to implantation,in order to provide a natural interface with flowing blood (47).Although initial results in terms of increased graft patency are promising, it is clear that this only partially simulates an actual,living blood vessel. Others have attempted to use the co-culture of endothelial cells and smooth mus- cle cells in the construction of an artificial blood vessel.Most notable is the effort of Weinberg et al.(42)who constructed an artificial blood vessel using bovine aortic en- dothelial cells,bovine aortic smooth muscle cells and advential fibroblasts.This was composed of three layers,one of endothelial cells,one of smooth muscle cells together538 R.M. Nerem One of the more promising areas of tissue engineering is in the development of bio￾logical substitutes based on the encapsulation of cultured cells. One of the important areas for use of encapsulated cell technology is in the development of bioartificial or￾gans, e.g., an artificial pancreas (20). Pancreas transplants have failed to be useful because of immunological rejection. An alternative approach is the development of implantable insulin pumps; however, these are not without problems either. This has led to the interest in developing a bioartificial pancreas (12). Although there are sev￾eral possible designs for a bioartificial pancreas, one involves the use of microencap￾sulated islet cells (31). In such a device, the islet cells, which secrete insulin, are surrounded by a semi-permeable membrane. This membrane must be permeable to the transport of insulin so it can be passed into the blood stream. The cells also will need nutrients, oxygen, and other molecules necessary for the maintenance of met￾abolic function. However, the membrane must, in addition, protect the islet cells from bacteria, lymphocytes, and other proteins responsible for immune rejection. Impor￾tant in the design of a bioartificial pancreas is its ability to respond rapidly to changes in glucose level. Equally necessary is the long term survival of the islet cells and the secretion of the insulin. As part of this, it also is important that islet cell function not change with a buildup of hormones. Although, in most of these areas, microencap￾sulated islet cells function quite well, one problem is that the insulin production rate is on the low side. There are other applications of encapsulated cell technology in tissue engineering. Cima et al. (11) have shown that both liver and cartilage ceils can be transplanted suc￾cessfully, at least in small animals, using cells which are encapsulated in a degrada￾ble polymer substrate. Neurological deficits also can be treated by transplantation within the brain of polymer encapsulated cells which release the missing neurotrans￾mitter, and Aebischer et al. (1) have investigated the ability of encapsulated dopamine secreting cells to reverse experimental Parkinson's disease. Finally a major tissue￾engineering market, where encapsulated cell technology may have application, is in the development of blood substitutes, i.e., an artificial blood (36). Current efforts are based on the chemical cross-linking of hemoglobin, in many cases bovine derived, but there are potential problems associated with both incomplete cross-linking and the in￾troduction of the foreign, bovine proteins into the body. In the future the use of mi￾croencapsulation, together with stem-cell culture and controlled hematopoiesis, should prove important. Another application of tissue engineering is in the development of an artificial blood vessel for use in the bypass and replacement of diseased arteries (24,42). A number of groups have been interested in applying cell culture technology to the de￾velopment of such tissue-engineered vascular prostheses. Much of this effort has been focused on hybrid vascular grafts, i.e., a graft constructed out of synthetic material such as dacron or polytetrafluoroethylene (PTFE), but seeded with cultured endothe￾lial cells prior to implantation, in order to provide a natural interface with flowing blood (47). Although initial results in terms of increased graft patency are promising, it is clear that this only partially simulates an actual, living blood vessel. Others have attempted to use the co-culture of endothelial cells and smooth mus￾cle cells in the construction of an artificial blood vessel. Most notable is the effort of Weinberg et al. (42) who constructed an artificial blood vessel using bovine aortic en￾dothelial cells, bovine aortic smooth muscle cells and advential fibroblasts. This was composed of three layers, one of endothelial cells, one of smooth muscle cells together