Define the design requirements and constraints for an immuno-isolation membrane to encapsulate isolated islets of Langerhans for pancreatic tissue engineering.

The design requirements and constraints must spring from the function of the immuno-isolation membrane. The membrane serves to isolate the islets without exposing them to the immune system, but still permitting them to work with certain other nutrients within the bloodstream.

The function we are concerned with is the detection of glucose levels and secretion of insulin in response. Thus, there must be pathways for the movement of glucose and insulin in and out of the system.

The danger is sensitisation of the body's immune system, which takes place if cells of the immune system, such as macrophages, or compliments, reach the foreign cells. These cells are typically larger than insulin, and certainly larger than glucose, so a membrane able to permit things with a molecular weight less than 8000 is required, that is to say, it must be controllably selective. The presence of third body biological artefacts, such as bacteria, is likely to further endanger the immune status of the system, as well as the health of the patient, and so sterility in the manufacturing and implantation is of great importance.

The total encapsulation of the cell is of great importance, this is because even a small part of an islet in contact with the host immune system can cause sensitisation and fibrotic attack around the whole capsule. The membrane likewise must be highly biocompatible, as any fibrotic response is likely to suffocate the islets inside, depriving them of nutrients, and not allowing the secretion of insulin into the host system.

In terms of the manufacturing process, the islets are living entities, and must be treated as such. The exposure to extremes of temperature or high mechanical stresses is likely to render them unviable. Further, the islets must be happy with their immediate environment, that is, the side contacting the islets must be biocompatible, just as the opposite side must be. It may be worth noting that the fibrotic response is not expected to be produced by the islets themselves.

The final concerns are those of surgical implantation. The first is size, the position on the portal vein means that area is limited, and large size compromises surgical precision. Thus a high cell density is preferential for minimisation of size and maintenance of functionality. Secondly, there are many concerns of safety, quality assurance, and monitoring which point towards the need for retrievability. The membrane further must stand up to the biological environment, against biological attack, chemical erosion, and physical stress. Finally the object must be surgically acceptable for the purposes of implantation.