Multiple membrane microencapsulation

Claim 1

A biocompatible microcapsule, having a diameter of about 400-500 m, comprising: a macromolecular core material comprising living tissue surrounded by a first biocompatible highly permeable hydrogel membrane consisting of ionically interacted biocompatible materials, having a molecular weight cut-off of about 200-400× 10 3 ; and said first membrane being interacted with ionically interacted biocompatible materials to form a second relatively less permeable hydrogel membrane having a molecular cut-off of about 40-80×10 3 ; said first membrane being sufficiently permeable to permit diffusion therethrough of that portion of a water soluble cross-linkable gelling agent used to suspend said living tissue and having a molecular weight of less than 200-400 ×10 3 , and permitting expansion of said microcapsule towards an equilibrium state; and said second membrane being sufficiently permeable to permit nutrients to flow from a medium in which said microcapsule is placed into said microcapsule to sustain said living tissue, and sufficiently impermeable to retain said living tissue and any high molecular weight product thereof within the microcapsule.

Claim 8

A method of encapsulating living tissue within two semi permeable hydrogel membranes which comprises: (a) mixing said living tissue with an aqueous solution of water soluble polymeric material which can be reversibly gelled and which has free acid groups. (b) forming said mixture into droplets and gelling said droplets in a hardening agent; (c) forming a first biocompatible highly permeable hydrogel membrane about said first gelled droplets to produce a first microcapsule by reaction with a polymer containing free amino groups; said first membrane having a molecular weight cut-off of 200-400×10 3 ; (d) suspending said first microcapsule in a medium which reliquifies said water soluble polymeric material; (e) incubating said first microcapsule in an aqueous medium for sufficient time to allow at least one third of that portion of said water soluble polymeric material having a molecular weight of less than 200-400×10 3 to diffuse out of said microcapsule, and to allow said microcapsule to expand towards an equilibrium state; (f) reacting said incubated first microcapsule with a polymer containing positively charged groups to thereby form an interacted relatively less permeable hydrogel membrane having a molecular weight cut-off of 40-80×10 3 ; and (g) incubating said living tissue within said interacted microcapsule in a nutrient medium; said interacted membrane being sufficiently permeable to permit passage of nutrients and sufficiently impermeable to retain said tissue and any high molecular weight products thereof within said second microcapsule.

Claim 9

A method of encapsulating living tissue within two semi permeable hydrogel membranes which comprises: (a) mixing said living tissue with an aqueous solution of water soluble polymeric material which can be reversibly gelled and which has free acid groups. (b) forming said mixture into droplets and gelling said droplets in a hardening agent; (c) forming a first biocompatible highly permeable hydrogel membrane about said first gelled droplets to produce a first microcapsule by reaction with a polymer containing free amino groups; said first membrane having a molecular weight cut-off of 200-400×10 3 ; (d) suspending said first microcapsule in a medium which reliquifies said water soluble polymeric material; (e) incubating said first microcapsule in an aqueous medium for sufficient time to allow at least one third of that portion of said water soluble polymeric material having a molecular weight of less than 200-400×10 3 to diffuse out of said microcapsule, and to allow said microcapsule to expand towards an equilibrium state; (f) reacting said incubated first microcapsule with a polymer containing positively charged groups to thereby form an interacted relatively less permeable hydrogel membrane having a molecular weight cut-off of 40-80×10 3 ; and (g) incubating said living tissue within said interacted microcapsule in a nutrient medium; said interacted membrane being sufficiently permeable to permit passage of nutrients and sufficiently impermeable to retain said tissue and any high molecular weight products thereof within said second microcapsule.