Microencapsulation of living tissue and cells

Claim 1

A biocompatible in microcapsule, suitable for implantation into an animal body and having a diameter of about 50 to about 2000 μm, comprising: a macromolecular spherical core containing living tissue or individual cells thereof, said core being surrounded by of interpenetrating layers of ionically-interacted biocompatible materials defining a membrane thickness of about 5 to about 20 μm, said biocompatible materials comprising a biocompatible polyamino acid polymer normally having a positively-charged surface and a non-toxic biocompatible water-soluble polymeric material which is capable of ionic interaction with free amino groups in said polyamino acid to provide an outer biocompatible negatively-charged surface, said biocompatible semi-permeable membrane being in the form of a hydrogel having an overall water content within the membrane structure of at least about 20 wt. %, said biocompatible semi-permeable membrane being permeable to and permitting nutrients and oxygen to flow from a body in which the microcapsule is implanted to said living tissue of individual cells thereof and permitting metabolic products of said living tissue to flow therefrom to the body in which the microcapsule is implanted and being impermeable to said living tissue to retain the living tissue within the microcapsule, said microcapsule being capable of resisting degradation and remaining permeable in vivo for at least two months.

Claim 7

A method of encapsulating a core material within a semi-permeable membrane which is a hydrogel having an overall water content within the membrane structure of at least about 20 wt. %, which method comprises: (a) placing the material in an aqueous solution of a water-soluble polymeric substance that can be reversibly gelled and which has free acid groups, (b) forming the solution into droplets, (c) gelling the droplets to produce discrete shape-retaining temporary capsules, (d) forming biocompatible semi-permeable membranes about the temporary capsules by contact between the temporary capsules and a biocompatible polyamino acid polymer containing free amino groups to cause ionic reaction with the acid groups in a surface layer of the capsule to provide a positively-charged surface, and (e) contacting said microcapsules formed in step (d) with a non-toxic biocompatible water soluble polymeric material which contains free negatively-charged groups capable of ionic reaction with the free amino groups of said polyamino acid polymer in surface layer of the microcapsule, thereby to form an outer coating of said biocompatible polymeric material on said microcapsules having a negatively-charged surface, said semi-permeable membrane formation and said contact thereof with biocompatible polymeric material being such as to form microcapsules having a diameter of about 50 to about 2000 μm and a semi-permeable membrane thickness of about 5 to about 20 μm, and being such as to produce microcapsules capable of resisting degradation and remaining permeable in vivo for at least two months.

Claim 8

A method of encapsulating a core material within a semi-permeable membrane which is a hydrogel having an overall water content within the membrane structure of at least about 20 wt. %, which method comprises: (a) placing the material in an aqueous solution of a water-soluble polymeric substance that can be reversibly gelled and which has free acid groups, (b) forming the solution into droplets, (c) gelling the droplets to produce discrete shape-retaining temporary capsules, (d) forming biocompatible semi-permeable membranes about the temporary capsules by contact between the temporary capsules and a biocompatible polyamino acid polymer containing free amino groups to cause ionic reaction with the acid groups in a surface layer of the capsule to provide a positively-charged surface, and (e) contacting said microcapsules formed in step (d) with a non-toxic biocompatible water soluble polymeric material which contains free negatively-charged groups capable of ionic reaction with the free amino groups of said polyamino acid polymer in surface layer of the microcapsule, thereby to form an outer coating of said biocompatible polymeric material on said microcapsules having a negatively-charged surface, said semi-permeable membrane formation and said contact thereof with biocompatible polymeric material being such as to form microcapsules having a diameter of about 50 to about 2000 μm and a semi-permeable membrane thickness of about 5 to about 20 μm, and being such as to produce microcapsules capable of resisting degradation and remaining permeable in vivo for at least two months.