Prosthetic grafts
AssigneeSulzer Biologics, Inc.
InventorsDiane Lee Anderson, John Paul Ranieri, Maurizio Capogrossi Colognesi, Marco Scoccianti, Antonio Facchiano
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Abstract
An improved prosthetic graft for the bypass, replacement or repair of vessels and organs that are in contact with blood flow is disclosed. The prosthetic graft includes a porous prosthetic implant and adherent cells adhered to the outer surface of the implant. The adherent cells are transfected with at least one recombinant nucleic acid molecule encoding at least one protein that enhances patency of the graft. The prosthetic graft has a long-term patency and success rate that is superior to other previously described prosthetic grafts designed for such use. Also disclosed are methods of making and using such a graft.
Claims59
A prosthetic graft for containment of blood flow in vivo, comprising:
- (a) a porous prosthetic implant for containing blood in vivo, said prosthetic implant having an outer surface that is not in contact with blood flow in vivo and an inner surface that is in contact with blood flow in vivo, said inner surface defining an interior space for containment of blood flow;
- and,
- (b) adherent cells adhered to the outer surface of said porous prosthetic implant, wherein said adherent cells are transfected with at least one recombinant nucleic acid molecule operatively linked to a transcription control sequence, said recombinant nucleic acid molecule encoding a protein wherein at least a portion of said protein, upon secretion from said cells, perfuses through pores of said prosthetic implant to said inner surface of said prosthetic implant, enhancing patency of said prosthetic implant.
A vascular graft, comprising:
- (a) a porous prosthetic vessel having a perivascular surface and a lumenal surface;
- and
- (b) adherent cells adhered to the perivascular surface of said porous prosthetic vessel, wherein said adherent cells are transfected with at least one recombinant nucleic acid molecule operatively linked to a transcription control sequence, said recombinant nucleic acid molecule encoding a protein wherein at least a portion of said protein, upon secretion from said cells, perfuses through pores of said prosthetic vessel to said lumenal surface of said prosthetic vessel, enhancing patency of said prosthetic vessel.
A prosthetic graft for containment of blood flow in vivo, comprising:
- (a) a porous prosthetic implant for containing blood in vivo, said prosthetic implant having an outer surface that is not in contact with blood flow in vivo and an inner surface that is in contact with blood flow in vivo, said inner surface defining an interior space for containment of blood flow;
- and,
- (b) adherent cells adhered to the outer surface of said porous prosthetic implant, wherein said adherent cells express and secrete at least one protein wherein at least a portion of said protein, upon secretion from said cells, perfuses through pores of said prosthetic implant to said inner surface of said prosthetic implant, enhancing patency of said prosthetic implant.
A method for producing a prosthetic graft, comprising applying adherent cells to a porous prosthetic implant for containing blood in vivo, wherein said prosthetic implant has an outer surface and an inner surface that defines an interior space for containment of blood flow;
- wherein said adherent cells are applied to said outer surface of said prosthetic implant;
- and,
- wherein said adherent cells are transformed with at least one recombinant nucleic acid molecule operatively linked to a transcription control sequence, said recombinant nucleic acid molecule encoding a protein wherein at least a portion of said protein, upon secretion from said cells, perfuses through pores of said prosthetic implant to said inner surface of said prosthetic implant, enhancing patency of said prosthetic implant.
A method of implantation of a prosthetic graft for containment of blood flow, comprising implanting a prosthetic graft into a patient, said prosthetic graft comprising:
- (a) a porous prosthetic implant for containing blood in vivo, said prosthetic implant having an outer surface and an inner surface defining an interior space for containment of blood flow;
- and,
- (b) adherent cells adhered to the outer surface of said porous prosthetic implant, wherein said adherent cells are transfected with at least one recombinant nucleic acid molecule operatively linked to a transcription control sequence, said recombinant nucleic acid molecule encoding a protein wherein at least a portion of said protein, upon secretion from said cells, perfuses through pores of said prosthetic implant to said inner surface of said prosthetic implant, enhancing patency of said prosthetic implant.
A method for implantation of a prosthetic graft for containing blood flow in a patient, comprising:
- (a) harvesting fibroblast cells from a patient in need of a prosthetic graft for containing blood flow;
- (b) transfecting said fibroblast cells with an isolated nucleic acid molecule encoding a protein that enhances patency of said graft;
- (c) applying said transfected fibroblast cells onto a surface of a prosthetic implant configured for containing blood flow in vivo for a time sufficient to allow said fibroblast cells to adhere to said surface to form a prosthetic graft, wherein said surface is not in contact with blood flow in vivo, wherein at least a portion of said protein, upon secretion from said cells, perfuses through pores of said prosthetic graft to a surface in contact with blood flow;
- (d) implanting said prosthetic graft into said patient.
A method of enhancing endothelialization of a vascular graft, comprising applying adherent cells to a porous prosthetic vessel having a perivascular surface and a lumenal surface, wherein said adherent cells are adhered to the perivascular surface of the prosthetic vessel;
- and
- wherein said adherent cells are transfected with at least one recombinant nucleic acid molecule operatively linked to a transcription control sequence, said recombinant nucleic acid molecule encoding a protein that enhances endothelialization of said prosthetic vessel;
- whereby said protein is expressed and secreted by said adherent cells and perfuses through pores in said prosthetic vessel to the lumenal surface of said prosthetic vessel to enhance endothelialization of said graft at said lumenal surface.
Dependencies are inferred from the claim text.