Chapter 27 - Engineering Challenges in Immunoisolation Device Development

Abstract

This chapter focuses on the engineering challenges involved in the attempt to make implantable immunoisolation devices a clinical reality. Engineering challenges exist in three areas: supply of tissue, protection from immune rejection, and maintenance of cell viability and function. There are various sources of tissue. Most common is primary tissue used immediately after isolation or following culture. With cultured cell lines, as with primary tissue, immunoisolation is easier to accomplish with allogeneic than with xenogeneic cells. However, some investigators prefer xenogeneic cell lines because such cells would be rejected by the host if the device broke and released unencapsulated cells, whereas allogeneic cells might not be so easily rejected, especially if they were tumorigenic. Prevention of cells entering the tissue compartment is easily achieved using microporous membranes. This may be the only requirement for immunoisolation of allogeneic tissue, at least for periods up to several months. With xenografts, keeping out components of the humoral immune response is more difficult to accomplish. Maintenance of cell viability and function is essential and is limited by the supply of nutrients and oxygen. Diffusion limitations of oxygen in tissue in vivo are far more severe than those of glucose because the concentration of glucose in tissue is higher. The requirements of specific tissues for other small molecules and for macromolecules are poorly understood or have not yet been quantified; transport limitations for large molecules are highly dependent on immunoisolation membrane properties, whereas oxygen limitations are always serious.