US2009035346A1PendingUtilityA1
Methods and Compositions for Enhancing Vascular Access
Est. expiryJun 21, 2025(expired)· nominal 20-yr term from priority
C12N 5/069A61L 27/3808
51
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
Disclosed is an implantable material comprising a biocompatible matrix and cells which, when provided to a vascular access structure, can promote functionality generally. For example, implantable material of the present invention can enhance maturation of an arteriovenous native fistula as well as prolong the fistula in a mature, functional state suitable for dialysis. Additionally, the present invention can promote formation of a functional arteriovenous graft suitable for dialysis as well as promote formation of a functional peripheral bypass graft. Implantable material can be configured as a flexible planar form or a flowable composition with shape-retaining properties suitable for implantation at, adjacent or in the vicinity of an anastomoses or arteriovenous graft. According to the methods disclosed herein, the implantable material is provided to an exterior surface of a blood vessel. Certain embodiments of the flexible planar form define a slot. The materials and methods of the present invention comprise cells, preferably endothelial cells or cells having an endothelial-like phenotype.
Claims
exact text as granted — not AI-modified1 . A method for treating a vascular access structure in a patient, the method comprising the step of locating at, adjacent or in the vicinity of the vascular access structure in said patient an implantable material comprising cells and a biocompatible matrix, wherein the implantable material is effective to promote functionality of said structure.
2 . The method of claim 1 wherein the vascular access structure is an arteriovenous native fistula, an arteriovenous graft, or a venous catheter.
3 . The method of claim 2 wherein the arteriovenous graft comprises a prosthetic bridge.
4 . The method of claim 2 wherein the catheter is an indwelling dual lumen catheter.
5 . The method of claim 1 wherein the vascular access structure is for dialysis.
6 . The method of claim 2 wherein treating the arteriovenous fistula promotes repetitive cannulation.
7 . The method of claim 1 wherein treating the vascular access structure promotes normal or near-normal blood flow through and downstream of the structure.
8 . The method of claim 7 wherein blood flow is at a rate sufficient to prevent re-circulation during hemodialysis.
9 . The method of claim 1 wherein treating the vascular access structure promotes normal or near-normal vessel diameter.
10 . The method of claim 1 wherein treating the vascular access structure reduces flow recirculation during hemodialysis.
11 . The method of claim 2 wherein treating the arteriovenous native fistula promotes clinical maturation sufficient to permit hemodialysis.
12 . The method of claim 2 wherein the implantable material reduces delay in maturation of the arteriovenous native fistula.
13 . The method of claim 2 wherein treating the arteriovenous graft promotes clinical stability sufficient to restore normal or near normal peripheral circulation.
14 . The method of claim 2 wherein treating the indwelling dual lumen catheter promotes clinical stability sufficient to permit hemodialysis.
15 . The method of claim 2 wherein the implantable material reduces the occurrence of revision in the patient.
16 . An implantable material comprising cells and a biocompatible matrix suitable for use with the method of claim 1 .
17 . The implantable material of claim 16 wherein the cells are endothelial cells or cells having an endothelial-like phenotype.
18 . The implantable material of claim 16 wherein the biocompatible matrix is a flexible planar material or a flowable composition.
19 . The implantable material of claim 18 wherein the flexible planar material is configured for implantation at an anastomosis.
20 . The implantable material of claim 19 wherein the material defines a slot.
21 . The implantable material of claim 19 wherein the material is configured as in FIG. 1 or 2 A.
22 . The implantable material of claim 18 wherein the flowable composition is a shape-retaining composition.
23 . A method for enhancing maturation of an arteriovenous fistula in a human, the method comprising the step of locating at, adjacent or in the vicinity of the fistula an implantable material comprising a biocompatible matrix and cells wherein the implantable material is effective to enhance maturation of the fistula.
24 . The method of claim 23 wherein enhancing maturation is characterized by an ability to repetitively cannulate the fistula for dialysis.
25 . The method of claim 23 wherein enhancing maturation is characterized by an ability to obtain sufficient blood flow during dialysis.
26 . The method of claim 25 wherein sufficient blood flow comprises a rate of about 350 ml/min.
27 . The method of claim 23 wherein the arteriovenous fistula is radiocephalic, brachiocephalic, or brachiobasilic.
28 . The method of claim 23 wherein application of the biocompatible material to the arteriovenous fistula is preceded by or coincident with administration of a therapeutic agent.
29 . The method of claim 23 wherein application of the biocompatible material to the arteriovenous fistula is preceded by physical dilatation.
30 . A method for preventing an arteriovenous fistula from failing to mature in a human, the method comprising the step of locating a biocompatible matrix comprising engrafted vascular endothelial cells at, adjacent or in the vicinity of the fistula in the human thereby to prevent a fistula from failing to mature.
31 . The method of claim 30 wherein failing to mature is characterized by an inability to repetitively cannulate the fistula for dialysis.
32 . The method of claim 30 wherein failing to mature is characterized by an inability to obtain sufficient blood flow during dialysis.
33 . The method of claim 32 wherein the sufficient blood flow comprises a rate of about 350 ml/min.
34 . The method of claim 30 wherein the arteriovenous fistula is radiocephalic, brachiocephalic, or brachiobasilic.
35 . The method of claim 30 wherein application of the biocompatible material to the arteriovenous fistula is preceded by or coincident with administration of a therapeutic agent.
36 . The method of claim 30 wherein application of the biocompatible material to the arteriovenous fistula is preceded by physical dilatation.
37 . The method of claim 31 wherein the arteriovenous fistula can not be cannulated at least 2 months after creation.
38 . The method of claim 31 wherein the arteriovenous fistula can not be cannulated at least 3 months after creation.
39 . The method of claim 31 wherein the arteriovenous fistula can not be cannulated at least 4 months after creation.
40 . An implantable material comprising cells and a biocompatible matrix suitable for use with the method of claim 23 .
41 . The implantable material of claim 40 wherein the cells are endothelial cells or cells having an endothelial-like phenotype.
42 . The implantable material of claim 40 wherein the biocompatible matrix is a flexible planar material or a flowable composition.
43 . The implantable material of claim 42 wherein the flexible planar material is configured for implantation at an anastomosis.
44 . The implantable material of claim 43 wherein the material defines a slot.
45 . The implantable material of claim 43 wherein the material is configured as in FIG. 1 or 2 A.
46 . The implantable material of claim 42 wherein the flowable composition is a shape-retaining composition
47 . A method of maintaining a blood flow rate of an arteriovenous graft, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said arteriovenous graft at, adjacent or in the vicinity of a prosthetic bridge of a venous outflow region of said arteriovenous graft in an amount effective to maintain blood flow rate of the graft.
48 . The method of claim 47 wherein the blood flow rate at the venous outflow region of said arteriovenous graft is substantially similar to the blood flow rate upstream of said outflow region; or wherein the blood flow rate is sufficient to permit dialysis.
49 . A method of maintaining normal blood flow of a peripheral bypass graft sufficient to maintain peripheral circulation, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said bypass graft at, adjacent or in the vicinity of a prosthetic bridge in an amount effective to maintain blood flow rates of the bypass graft sufficient to maintain peripheral circulation.
50 . The method of claim 49 wherein an inflow blood rate and an outflow blood rate are substantially similar.
51 . A method of promoting tissue integration of a prosthetic bridge of an arteriovenous graft or a peripheral bypass graft, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said arteriovenous graft or said peripheral bypass graft at, adjacent or in the vicinity of a prosthetic bridge in an amount effective to promote tissue integration of said bridge.
52 . The method of claim 51 wherein said implantable material promotes smooth muscle cell proliferation or migration within or in the vicinity of an interior lumen surface of said prosthetic bridge.
53 . The method of claim 51 wherein said implantable material promotes endothelial cell proliferation or migration within or in the vicinity of an interior lumen surface of said prosthetic bridge.
54 . A method of preventing or reducing the incidence of dehiscence of an arteriovenous fistula or arteriovenous graft, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said fistula or arteriovenous graft at, adjacent or in the vicinity of a prosthetic bridge of a venous outflow region of said arteriovenous graft in an amount effective to prevent or reduce the incidence of dehiscence.
55 . The method of claim 47 wherein the providing step is performed as an interventional therapy following failure of a native arteriovenous fistula.
56 . The method of claim 49 wherein the providing step is performed as an interventional therapy following failure of a native or saphenous vein peripheral bypass.
57 . An implantable material comprising:
(a) cells; and, (b) a biocompatible matrix;
wherein said implantable material is disposed in the vicinity of, adjacent or contacting a prosthetic bridge; and
wherein said prosthetic bridge is situated at or near a venous outflow region of an arteriovenous graft or is situated at or near an outflow of a peripheral bypass graft.
58 . A method of maintaining a blood pressure of an arteriovenous graft sufficient to permit dialysis, the method comprising the step of providing an implantable material comprising cells and a biocompatible matrix wherein said implantable material is disposed on an exterior surface of said arteriovenous graft at, adjacent or in the vicinity of a prosthetic bridge of a venous outflow region of said arteriovenous graft in an amount effective to maintain blood pressure sufficient to permit dialysis.
59 . The method of claim 58 wherein the blood pressure at the venous outflow region of said arteriovenous graft is substantially similar to the blood pressure upstream of said outflow region.
60 . The method of claim 58 wherein the prosthetic bridge is selected from the group consisting of: saphenous vein; bovine heterograft; umbilical vein; dacron; PTFE; ePTFE; polyurethane; bovine mesenteric vein; and cryopreserved femoral vein allograft.
61 . The method of claim 60 wherein the prosthetic bridge is ePTFE.
62 . An implantable material comprising cells and a biocompatible matrix suitable for use with the method of claim 47 or 58 .
63 . The implantable material of claim 62 wherein the cells are endothelial cells or cells having an endothelial-like phenotype.
64 . The implantable material of claim 62 wherein the biocompatible matrix is a flexible planar material or a flowable composition.
65 . The implantable material of claim 64 wherein the flexible planar material is configured for implantation at, adjacent or in the vicinity of an anastomosis.
66 . The implantable material of claim 65 or 66 wherein the flexible planar material is configured for implantation at, adjacent or in the vicinity of an arteriovenous graft.
67 . The implantable material of claim 65 or 66 wherein the material defines a slot.
68 . The implantable material of claim 65 or 66 wherein the material is configured as in FIG. 1 or 2 A.
69 . The implantable material of claim 64 wherein the flowable composition is a shape-retaining composition.
70 . The implantable material of claim 16 , 17 , 40 or 57 wherein the cells are selected from the group consisting of: a confluent population of cells; a near confluent population of cells; a post confluent population of cells; and cells which have a phenotype of any one of the foregoing population of cells.
71 . A transport media composition for storing an implantable material comprising a biocompatible matrix and engrafted cells, said transport media composition comprising an amount of VEGF sufficient to maintain cell viability or an inhibitory phenotype, wherein the cells remain viable for an extended period of time when stored in said transport media composition at temperatures below the cells' standard cell culture temperature.
72 . The transport media composition of claim 71 wherein the amount of VEGF sufficient to maintain cell viability or an inhibitory phenotype at a temperature below the cells' standard cell culture temperature is greater than the amount of VEGF required at the cells' standard cell culture temperature.
73 . The transport media composition of claim 71 wherein the implantable material is stored in said transport media composition at a temperature below about 37° C.
74 . The transport media composition of claim 71 wherein the implantable material is stored in said transport media composition at ambient temperature.
75 . The transport media composition of claim 71 wherein cell viability is at least about 80%.
76 . The transport media composition of claim 71 wherein the cells, at the time of storage, are near-confluent, confluent, or post-confluent.
77 . The transport media composition of claim 71 wherein the extended period of time is about 1 week.
78 . The transport media composition of claim 71 wherein the extended period of time is about 2 weeks.
79 . The transport media composition of claim 71 wherein the extended period of time is about 3 weeks.
80 . The transport media composition of claim 71 wherein the cells are endothelial cells or endothelial-like cells.
81 . The transport media composition of claim 71 wherein the amount of VEGF is about 4 ng/mL.
82 . A cryopreservation media composition for cryopreserving an implantable material comprising a biocompatible matrix and engrafted cells, said cryopreservation media composition comprising a cryopreservative, a polysaccharide and serum, wherein cell viability or an inhibitory phenotype and matrix integrity are maintained for an extended period of time when stored at least about −4° C.
83 . The cryopreservation media composition of claim 82 wherein the amount of serum in said cryopreservation media composition exceeds the amount of serum for routine culturing of the cells.
84 . The cryopreservation media composition of claim 82 comprising at least about 20% serum.
85 . The cryopreservation media composition of claim 82 comprising at least about 50% serum.
86 . The cryopreservation media composition of claim 82 wherein the serum is fetal bovine serum.
87 . The cryopreservation media composition of claim 82 wherein the polysaccharide in said cryopreservation media composition exceeds the amount of polysaccharide for routine culturing of the cells.
88 . The cryopreservation media composition of claim 82 comprising at least about 2-8% polysaccharide.
89 . The cryopreservation media composition of claim 82 comprising at least about 4.5% polysaccharide.
90 . The cryopreservation media composition of claim 82 wherein the polysaccharide is dextran.
91 . The cryopreservation media composition of claim 82 further comprising about 10% DMSO.
92 . The cryopreservation media composition of claim 82 wherein storage is at least about −20° C.
93 . The cryopreservation media composition of claim 82 wherein storage is at least about −80° C.
94 . The cryopreservation media composition of claim 82 wherein storage is at least about −140° C.
95 . The cryopreservation media composition of claim 82 wherein said extended period of time is about 1 month.
96 . The cryopreservation media composition of claim 82 wherein said extended period of time is about 6 months.
97 . The cryopreservation media composition of claim 82 wherein said extended period of time is about 1 year.
98 . The cryopreservation media composition of claim 82 wherein cell viability is at least about 80%.
99 . A cryopreserved implantable material comprising a biocompatible matrix engrafted with cells and a volume of cryopreservation media composition sufficient to maintain cell viability or an inhibitory phenotype and matrix integrity while cryopreserved, wherein said cryopreservation media composition comprises a cryopreservative, a polysaccharide and serum.
100 . A method for storing an implantable material comprising a biocompatible matrix and engrafted cells for an extended period of time at a temperature below the cells' standard cell culture temperature, said method comprising the steps of:
bathing the implantable material in a transport media composition comprising an amount of VEGF sufficient to maintain cell viability or an inhibitory phenotype during storage, wherein the cells remain viable or maintain an inhibitory phenotype for an extended period of time when stored in said transport media composition at a temperature below the cells' standard cell culture temperature.
101 . The method of claim 100 wherein the amount of VEGF sufficient to maintain cell viability or an inhibitory phenotype at a temperature below the cells' standard cell culture temperature is greater than the amount of VEGF required at the cells' standard cell culture temperature.
102 . The method of claim 100 wherein the ratio of volume of transport media composition to volume of implantable material is about 50:1.
103 . The method of claim 100 wherein the volume of transport media composition is about 50 mL.
104 . The method of claim 100 wherein the transport media composition pH is about 7.4.
105 . The method of claim 100 wherein the implantable material is stored in said transport media composition at a temperature below about 37° C.
106 . The method of claim 100 wherein the implantable material is stored in said transport media composition at ambient temperature.
107 . The method of claim 100 wherein cell viability is at least about 80%.
108 . The method of claim 100 wherein the cells, at the time of storage, are near-confluent, confluent, or post-confluent.
109 . The method of claim 100 wherein the extended period of time is about 1 week.
110 . The method of claim 100 wherein the extended period of time is about 2 weeks.
111 . The method of claim 100 wherein the extended period of time is about 3 weeks.
112 . The method of claim 100 wherein the cells are endothelial cells or endothelial-like cells.
113 . The method of claim 100 wherein the amount of VEGF is about 4 ng/mL.
114 . A method for cryopreserving an implantable material comprising a biocompatible matrix and engrafted cells for an extended period of time at a temperature about −4° C., said method comprising the steps of:
bathing the implantable material in a cryopreservation media composition comprising a cryopreservative, a polysaccharide and serum, wherein the cells remain viable or maintain an inhibitory phenotype and the matrix remains intact for an extended period of time when stored in said cryopreservation media composition at a temperature about −4° C.
115 . The cryopreservation method of claim 114 wherein the amount of serum in said cryopreservation media composition exceeds the amount of serum for routine culturing of the cells.
116 . The cryopreservation method of claim 114 wherein the cryopreservation media composition comprises at least about 20% serum.
117 . The cryopreservation method of claim 114 wherein the cryopreservation media composition comprises at least about 50% serum.
118 . The cryopreservation method of claim 114 wherein the serum is fetal bovine serum.
119 . The cryopreservation method of claim 114 wherein the polysaccharide in said cryopreservation media composition exceeds the amount of polysaccharide for routine culturing of the cells.
120 . The cryopreservation method of claim 114 wherein the cryopreservation media composition comprises at least about 2-8% polysaccharide.
121 . The cryopreservation method of claim 114 wherein the cryopreservation media composition comprises at least about 4.5% polysaccharide.
122 . The cryopreservation method of claim 114 wherein the polysaccharide is dextran.
123 . The cryopreservation method of claim 114 wherein the cryopreservation media composition further comprises about 10% DMSO.
124 . The cryopreservation method of claim 114 wherein the ratio of volume of cryopreservation media composition to volume of implantable material is about 5:1.
125 . The cryopreservation method of claim 114 wherein the volume of cryopreservation media composition is about 5 mL.
126 . The cryopreservation method of claim 114 wherein storage is at least about −80° C.
127 . The cryopreservation method of claim 114 wherein storage is at least about −140° C.
128 . The cryopreservation method of claim 114 wherein storage is at least about −160° C.
129 . The cryopreservation method of claim 114 wherein said extended period of time is about 1 month.
130 . The cryopreservation method of claim 114 wherein said extended period of time is about 6 months.
131 . The cryopreservation method of claim 114 wherein said extended period of time is about 1 year.
132 . The cryopreservation method of claim 114 wherein cell viability is at least about 80%.
133 . A method of preparing an implantable material comprising a biocompatible matrix and engrafted cells, said method comprising the steps of:
preparing a working cell bank; providing a hydrated biocompatible matrix material; seeding the hydrated biocompatible matrix material with cells from the working cell bank; placing the cell seeded biocompatible matrix material in an incubator to facilitate cell attachment; placing the cell seeded biocompatible matrix material in an incubator until the cells are near-confluent, confluent, or post-confluent; and assessing cell count, cell viability and/or cell functionality of the cell seeded biocompatible matrix material.
134 . The method of claim 133 further comprising the steps of:
placing the cell seeded biocompatible matrix material in a vial suitable for cryopreservation; and introducing to the near-confluent, confluent, or post-confluent cell seeded biocompatible matrix material a volume of cryopreservation media composition comprising a cryopreservative, a polysaccharide and serum sufficient to preserve cell viability or an inhibitory phenotype and matrix integrity while the material is cryopreserved.
135 . The method of claim 134 further comprising the steps of:
placing the vial containing the cell seeded biocompatible matrix material and cryopreservation media composition in a freezing container; introducing an agent which controls the freezing rate to the freezing container; placing the freezing container containing said agent in a freezer at least about −4° C.; removing the freezing container from the at least about −4° C. freezer; and placing the freezing container in a freezer at least about −80° C.
136 . The method of claim 135 further comprising the steps of:
removing the freezing container from the at least about −80° C. freezer; and placing the vial in a freezer at least about −160° C.
137 . The method of claim 136 further comprising the steps of:
removing the vial from the freezer; placing the vial in ambient temperature air for about 15 minutes followed by placing the vial in an ambient temperature water bath for about 15 minutes; removing the implantable material from the vial; rinsing the implantable material in a rinse media composition for about 5 minutes; and placing the implantable material in cell culture media for about 48 hours.
138 . The method of claim 136 further comprising the steps of:
removing the vial from the freezer; placing the vial in ambient temperature air for about 15 minutes followed by placing the vial in an ambient temperature water bath for about 15 minutes; removing the implantable material from the vial; and rinsing the implantable material in a rinse solution composition for about 30 minutes.
139 . The method of claim 133 further comprising the steps of:
placing the cell seeded biocompatible matrix material in a vial suitable for storage; and introducing to the near-confluent, confluent, or post-confluent cell seeded biocompatible matrix material a volume of transport media composition comprising an amount of VEGF sufficient to maintain cell viability or an inhibitory phenotype while the material is stored in said composition.
140 . The method of claim 133 further comprising the steps of:
preparing the cell seeded biocompatible matrix material for cryopreservation according to the method of claim 134 or for storage according to the method of claim 139 ; preparing the vial for transport; transporting the vial to a clinical site for administration to a patient.
141 . The method of claim 140 further comprising the steps of:
placing the vial containing the cell seeded biocompatible matrix material into into an inner box; placing the inner box into an insulated outer box; and, providing product documentation.
142 . The method of claim 140 wherein the cell seeded biocompatible matrix material is clinical trial material and wherein the patient is a participant in a clinical trial.
143 . The method of claim 133 wherein the implantable material is prepared on a commercial scale.
144 . A robotic system to perform the method of any one or more of claims 133 - 141 .
145 . A method of manufacturing an implantable material comprising cells and a biocompatible matrix, said method comprising the step of:
contacting said biocompatible matrix with said cells using reagents and conditions suitable therefor, wherein said cells are in an amount sufficient to populate said matrix and grow to a confluent, near-confluent or post-confluent population and further wherein said matrix is populated with cell typing-independent, non-compatibility tested, non-matched cells.
146 . A method of treatment, said method comprising the step of:
providing an implantable material manufactured according to the method of claim 145 .
147 . An implantable material comprising cells and a biocompatible matrix manufactured according to the method of claim 145 .Join the waitlist — get patent alerts
Track US2009035346A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.