Microencapsulation of living tissue and cells
First Claim
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1. A biocompatible microcapsule, suitable for implantation into an animal body and having a diameter of about 50 to about 2000 μ
- m, comprising;
a macromolecular spherical core containing living tissue or individual cells thereof, said core being surrounded by a biocompatible semi-permeable membrane, said membrane consisting of interpenetrating layers of ionically interacted polylysine and alginate defining a membrane thickness of about 5 to about 20 μ
m, 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. %, the exterior of said membrane having an outer biocompatible negatively charged surface,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 or 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.
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Abstract
Living tissue or cells, for example, islets of Langerhans, are microencapsulated for implantation in the body for long term treatment of diabetes or other disease requiring organ transplantation. The microcapsules take the form of a biocompatible semi-permeable hydrogel membrane which permits the passage of materials and oxygen to the cells and metabolic products from the cells while retaining the cells encapsulated. The biocompatible semi-permeable membrane has an outer negatively-charged surface, which imparts to the microcapsules the ability to maintain long term effectiveness.
148 Citations
18 Claims
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1. A biocompatible microcapsule, suitable for implantation into an animal body and having a diameter of about 50 to about 2000 μ
- m, comprising;
a macromolecular spherical core containing living tissue or individual cells thereof, said core being surrounded by a biocompatible semi-permeable membrane, said membrane consisting of interpenetrating layers of ionically interacted polylysine and alginate defining a membrane thickness of about 5 to about 20 μ
m, 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. %, the exterior of said membrane having an outer biocompatible negatively charged surface,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 or 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. - View Dependent Claims (2, 3, 4, 5)
- m, comprising;
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6. 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:
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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 discreet shape-retaining temporary capsules, d. forming biocompatible semi-permeable membranes about the temporary capsules by contact for at least 6 minutes between the temporary capsules and a polylysine polymer containing free amino groups to cause ionic reaction with the acid groups and the surface layer of the capsule, and e. contacting said microcapsules formed in step d with a biocompatible polymeric material which contains free negatively charged groups capable of ionic reaction with the free amino groups in a surface layer of the microcapsule, thereby forming an outer coating of said biocompatible polymeric material on said microcapsules, 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 2,000 um and a semi-permeable membrane thickness of about 5 to about 20 um, and being such as to produce microcapsules capable of resisting degradation and remaining permeable in vivo for at least two months. - View Dependent Claims (7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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Specification