1. Field of the Invention
The present invention concerns a microcapsule generating system and relates to encapsulation of material generally, and more particularly to encapsulating tissue or a suspension of cells so that the encapsulated tissue or cells remain viable within a protective membrane or coating. The membrane or coating is permeable to nutrients, ions, oxygen, and other materials needed both to maintain the tissue and to support its normal metabolic functions, but is impermeable to bacteria, lymphocytes, and large proteins of the type responsible for immunological reactions resulting in rejection.
Insulin-producing or other hormone-producing systems, cells from tissues, primary cultured cells, cultured cell lines that produce biological products of interest (such as Factor VIII and calcitonin), and genetically engineered cultured cell lines, for example, can be coated using the encapsulating apparatus of the present invention. That is, this apparatus permits encapsulation of mammalian pancreatic beta cells, alpha cells, intact islets of Langerhans, and other tissues or tissue fractions which secrete hormones. The encapsulated cells or tissue may be suspended in a culture medium where they will secrete hormones over an extended period.
2. Background Art and Related Art Disclosures
Various attempts have been made to provide semipermeable microcapsules that were both biocompatible with the body tissue and impermeable to the components of the immune system. Typically, living tissue or individual cells are suspended in an aqueous solution of a reversibly gelable material, such as sodium alginate, and droplets of this suspension are formed and allowed to fall into a gelling solution, such as calcium chloride. The temporary capsules so formed are then treated with a crosslinking polymer, such as polylysine and polyethyleneimine, to form an outer semipermeable coating.
The droplets are typically formed by feeding the alginate suspension to a first site where a mass of the liquid suspension accumulates. Then the mass of liquid suspension is agitated such that it is broken up into small droplets. Devices using vibration, centrifugal force, air currents and electrostatic charges have been used to agitate the liquid to generate the small droplets.
One drawback of conventional devices using vibration, centrifugal force and air currents is that the diameters of the microcapsules produced thereby are dependent on the sizes of the orifices through which the suspension is extruded and are typically 500 .mu.m or greater with devices used for pancreatic islet encapsulation, where a relatively large bore diameter is dictated by the large size of islets (50-300 .mu.m). Since oxygen diffusion is insufficient to maintain cell viability at distances exceeding about 150 .mu.m, the cells in the center region of these microcapsules are routinely lost due to oxygen deprivation.
Although devices using electrostatic charges are claimed to produce microcapsules having diameters as small as 150 .mu.m (see, e.g., U.S. Pat. No. 4,789,550 to Hommel, et al.), the blank microcapsules and microcapsules containing cells or tissue produced by electrostatic devices generally are the same size. Accordingly, the separation and differentiation between the blanks and the other microcapsules is difficult at best. In addition, in order to produce microcapsules of small diameter using this approach, it is necessary to use small bore needles which cannot accommodate the larger particles in the suspension and which tend to clog with high density cell or other particulate suspensions.