Modified alginates for cell encapsulation and cell therapy
AssigneesMassachusetts Institute of Technology, Children's Medical Center Corporation
InventorsArturo J. Vegas, Minglin Ma, Kaitlin M Bratlie, Daniel G. Anderson, Robert S. Langer
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Abstract
Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for the encapsulation and transplantation of cells. Also disclosed are high throughput methods for the characterizing the biocompatibility and physiochemical properties of modified alginate polymers.
Claims31
A cell encapsulated by alginate comprising a modified alginate, wherein the modified alginate comprises one or more modified alginate monomers having a structure of Formula I:
- wherein:
- X is oxygen or sulfur, or NR;
- R1 is substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, polyaryl, or substituted polyaryl;
- Y1 and Y2 independently are hydrogen or —PO(OR)2;
- or Y2 is absent, and Y1, together with the two oxygen atoms to which Y1 and Y2 are attached form a cyclic structure as shown below
- R2 and R3 are, independently, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C3-C20 cyclic, substituted C3-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, poly(ethylene glycol), peptide, or polypeptide group;
- or R2 and R3, together with the carbon atom to which they are attached, form a 3- to 8-membered unsubstituted or substituted carbocyclic or heterocyclic ring;
- R is, independently for each occurrence, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, polyaryl, substituted polyaryl, C3-C20 cyclic, substituted C3-C20 cyclic, heterocyclic, or substituted heterocyclic;
- wherein the modified alginate has a molecular weight between about 10,000 Da and about 500,000 Da and the ratio of guluronate to mannuronate (G/M) of the modified alginate is greater than about 1:1.
A method of treating a patient, comprising transplanting a cell encapsulated in a modified alginate wherein the modified alginate comprises one or more modified alginate monomers having a structure of Formula (I):
- wherein:
- X is oxygen or sulfur, or NR;
- R1 is substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, polyaryl, or substituted polyaryl;
- Y1 and Y2 independently are hydrogen or —PO(OR)2;
- or Y2 is absent, and Y1, together with the two oxygen atoms to which Y1 and Y2 are attached form a cyclic structure as shown below
- R2 and R3 are, independently, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C3-C20 cyclic, substituted C3-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, poly(ethylene glycol), peptide, or polypeptide group;
- or R2 and R3, together with the carbon atom to which they are attached, form a 3- to 8-membered unsubstituted or substituted carbocyclic or heterocyclic ring;
- R is, independently for each occurrence, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, polyaryl, substituted polyaryl, C3-C20 cyclic, substituted C3-C20 cyclic, heterocyclic, or substituted heterocyclic;
- wherein the modified alginate has a molecular weight between about 10,000 Da and about 500,000 Da, and the ratio of guluronate to mannuronate (G/M) of the modified alginate is greater than about 1:1.
A cell encapsulated by a modified alginate, wherein the modified alginate comprises one or more covalently modified monomers selected from
A method of treating a patient, comprising transplanting a cell encapsulated in a modified alginate wherein the modified alginate comprises one or more covalently modified monomers selected from
A cell encapsulated by a modified alginate, wherein the modified alginate comprises one or more modified alginate monomers having a structure of Formula I:
- wherein:
- X is oxygen or sulfur, or NR;
- R1 is substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, polyaryl, or substituted polyaryl, C3-C20 cyclic, substituted C3-C20 cyclic, heterocyclic, or substituted heterocyclic, wherein when R1 is heterocyclic or substituted heterocyclic the modified alginate has a contact angle greater than 90°;
- Y1 and Y2 independently are hydrogen or —PO(OR)2;
- or Y2 is absent, and Y1, together with the two oxygen atoms to which Y1 and Y2 are attached form a cyclic structure as shown below
- R2 and R3 are, independently, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C3-C20 cyclic, substituted C3-C20 cyclic, heterocyclic, substituted heterocyclic, amino acid, poly(ethylene glycol), peptide, or polypeptide group;
- or R2 and R3, together with the carbon atom to which they are attached, form a 3- to 8-membered unsubstituted or substituted carbocyclic or heterocyclic ring;
- and
- R is, independently for each occurrence, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, polyaryl, substituted polyaryl, C3-C20 cyclic, substituted C3-C20 cyclic, heterocyclic, or substituted heterocyclic.
Dependencies are inferred from the claim text.