U.S. patent application number 17/695170 was filed with the patent office on 2022-06-30 for aortoiliac implant and processing and uses thereof.
This patent application is currently assigned to LifeNet Health. The applicant listed for this patent is LifeNet Health. Invention is credited to Alyce Linthurst Jones, Perry L. Lange, Eric Moore, Rex Nagao, Jason B. Schulte.
Application Number | 20220202556 17/695170 |
Document ID | / |
Family ID | |
Filed Date | 2022-06-30 |
United States Patent
Application |
20220202556 |
Kind Code |
A1 |
Jones; Alyce Linthurst ; et
al. |
June 30, 2022 |
AORTOILIAC IMPLANT AND PROCESSING AND USES THEREOF
Abstract
The present invention provides a package comprising an
aortoiliac artery graft and a record of a measured pressurized
diameter of the aortoiliac artery graft, which measurement has been
determined ex vivo under a pressure. A method of processing an
aortoiliac artery graft is also provided. The processing method
comprises subjecting an aortoiliac artery to a pressure ex vivo,
and determining a measured pressurized diameter of the aortoiliac
artery under the pressure. A method of treating abdominal aortic
aneurysm, infected aortoiliac endograft or a traumatically damaged
abdominal aorta or an iliac artery in a patient is further
provided. The treatment method comprises anastomosing a processed
aortoiliac artery graft with an aorta of the patient on the
proximal end and the iliac or femoral arteries on the distal end,
wherein a measured pressurized diameter of the processed aortoiliac
artery graft has been determined ex vivo under a pressure.
Inventors: |
Jones; Alyce Linthurst;
(Virginia Beach, VA) ; Schulte; Jason B.;
(Virginia Beach, VA) ; Moore; Eric; (Virginia
Beach, VA) ; Lange; Perry L.; (Virginia Beach,
VA) ; Nagao; Rex; (Virginia Beach, VA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
LifeNet Health |
Virginia Beach |
VA |
US |
|
|
Assignee: |
LifeNet Health
Virginia Beach
VA
|
Appl. No.: |
17/695170 |
Filed: |
March 15, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16329898 |
Mar 1, 2019 |
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PCT/US2018/051800 |
Sep 19, 2018 |
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17695170 |
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62560463 |
Sep 19, 2017 |
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International
Class: |
A61F 2/06 20060101
A61F002/06 |
Claims
1. A package comprising an artery graft and a first record, wherein
the first record provides a measured pressurized diameter of the
artery graft, and wherein the measured pressurized diameter has
been determined ex vivo under a pressure.
2. The package of claim 1, wherein the measured pressurized
diameter is a measured pressurized outer diameter of the artery
graft.
3. The package of claim 1, wherein the measured pressurized
diameter is a measured pressurized inner diameter of the artery
graft.
4. The package of claim 1, wherein the measured pressurized
diameter consists of a measured pressurized outer diameter of the
artery graft and a measured pressurized inner diameter of the
artery graft.
5. The package of claim 1, further comprising a second record,
wherein the second record provides a measured unpressurized
diameter of the artery graft, wherein the unpressurized diameter
has been determined ex vivo during processing.
6. The package of claim 5, wherein the measured unpressurized
diameter is a measured unpressurized outer diameter of the artery
graft.
7. The package of claim 5, wherein the measured unpressurized
diameter is a measured unpressurized inner diameter of the artery
graft.
8. The package of claim 5, wherein the measured unpressurized
diameter consists of a measured unpressurized outer diameter of the
artery graft and a measured unpressurized inner diameter of the
artery graft.
9. The package of claim 4, further comprising a second record,
wherein the second record provides a measured unpressurized
diameter of the artery graft, wherein the unpressurized diameter
has been determined ex vivo during processing.
10. The package of claim 9, wherein the measured unpressurized
diameter is a measured unpressurized outer diameter of the artery
graft.
11. The package of claim 9, wherein the measured unpressurized
diameter is a measured unpressurized inner diameter of the artery
graft.
12. The package of claim 9, wherein the measured unpressurized
diameter consists of a measured unpressurized outer diameter of the
artery graft and a measured unpressurized inner diameter of the
artery graft.
13. The package of claim 1, wherein the artery graft further
comprises a major artery selected from the group consisting of
celiac, superior and inferior mesenteric and renal arteries.
14. The package of claim 1, wherein the artery graft further
comprises a minor artery.
15. A method of processing an artery graft, comprising (a)
subjecting an artery to a pressure ex vivo during processing, and
(b) determining a measured pressurized diameter of the artery under
the pressure, whereby a processed artery graft is obtained.
16. The method of claim 15, wherein the pressure is controlled by
using a pressure relief valve or a calibrated syringe.
17. The method of claim 16, wherein the measured pressurized
diameter is determined by using a tool selected from the group
consisting of a ruler, a caliper, an umbilical tape, a laser
micrometer and ultrasound.
18. The method of claim 15, wherein the pressurized diameter is a
measured pressurized outer diameter of the artery.
19. The method of claim 15, wherein the pressurized diameter is a
measured pressurized inner diameter of the artery.
20. A processed artery graft prepared according to the method of
claim 15.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation application of U.S. application Ser.
No. 16/329,898, filed Mar. 1, 2019, claiming priority to U.S.
National Phase Application of International Application No.
PCT/US2018/051800, filed on Sep. 19, 2018, which claims the benefit
of U.S. Provisional Application No. 62/560,463, filed Sep. 19,
2017, the contents of which are incorporated herein by reference in
their entireties for all purposes.
FIELD OF THE INVENTION
[0002] The invention relates generally to aortoiliac artery (AI)
grafts and processing and uses thereof.
BACKGROUND OF THE INVENTION
[0003] Although widely used for treatment of abdominal aortic
aneurysm (AAA), synthetic vascular grafts often cause primary
infection and aortic graft-enteric erosion and present a serious
risk of mortality and morbidity (limb loss, recurrent infections
and paralysis). Cryopreserved, decellularized and devitalized
aortoiliac artery (AI) grafts are an ideal solution to replace
infected synthetic grafts. Given the severity of surgical cases,
clinicians must intervene quickly or the patient will likely
succumb to sepsis. Matching the size and configuration of an
aortoiliac artery (AI) graft with a patient's aorta in need of
surgery is critical to a successful surgery and long-term outcomes.
A wide variation exists in graft inner diameter (ID) and the
resultant outer diameter (OD) under arterial pressures vs in the
flaccid or unpressurized state from person to person, or donor to
donor. In other words, a flaccid inner diameter will produce a
variety of pressurized inner/outer dimeters, in a donor dependent
fashion, when subjected to arterial pressures. An unexpected
relationship between flaccid and pressurized diameters is that
smaller diameter aortas are more distensible than their larger
diameter counterparts measured at the same anatomical location
immediately distal to the diaphragm. Therefore, using a "one size
fits all" approach to develop a single multiplier value to apply to
a flaccid outer or inner diameter to predict the required
post-implant pressurized outer/inner diameter is not conducive to a
satisfactory surgical outcome because of this unexpected finding.
Diameter variability may lead to patient mismatch with AI grafts
leading to early failure as a result of non-laminar blood flow or
extended surgical times to surgically manipulate the receiving
aorta and AI to achieve the best possible match between them thus
increasing the risk of adverse events and increased healthcare
costs. As such, it is highly desirable to have accurate
measurements of pressurized AI graft ID or OD taken at time of
graft processing for better patient matches. Such accurate ID or OD
measurements would improve and shorten preoperative planning;
minimize risk during surgery by eliminating the extra time needed
to fashion an otherwise ill-fitting graft to the anastomotic site;
and likely result in more favorable outcomes since a size-matched
graft will avoid hemodynamic disruptions which occur with abrupt
changes in the diameter of the vascular conduit due to mismatched
grafts. None of the allograft AI grafts currently commercially
available provides pressurized ID or OD measurements. Thus, there
is a need for aortoiliac artery (AI) grafts of multiple
configurations and accurate pressurized diameter measurements to
match patients' aorta for use in clinical cases where aortic
reconstruction, repair, or replacement is necessary.
SUMMARY OF THE INVENTION
[0004] The present invention relates to an aortoiliac artery graft
with a measured pressurized diameter, and processing and uses
thereof.
[0005] A package comprising an aortoiliac artery graft and a first
record is provided. The first record provides a measured
pressurized diameter of the aortoiliac artery graft, and the
measured pressurized diameter has been determined ex vivo under a
pressure. The measured pressurized diameter may be a measured
pressurized outer diameter of the aortoiliac artery graft. The
measured pressurized diameter may be a measured pressurized inner
diameter of the aortoiliac artery graft. The pressure may be in a
range of 120-140 mmHg.
[0006] The package may further comprise a second record. The second
record may provide a measured unpressurized diameter of the
aortoiliac artery graft, and the unpressurized diameter may have
been determined ex vivo. The measured unpressurized diameter may be
a measured unpressurized outer diameter of the aortoiliac artery
graft. The measured unpressurized diameter may be a measured
unpressurized inner diameter of the aortoiliac artery graft.
[0007] In the package, the aortoiliac artery graft may comprise a
full aortoiliac artery, an abdominal aorta distal to renal arteries
inclusive of iliac arteries to an iliofemoral junction, or an
abdominal aorta distal of renal arteries and inclusive of at least
1 cm of an iliac artery.
[0008] The aortoiliac artery may comprise a distal aorta and iliacs
without renal arteries. The aortoiliac graft may comprise an aorta
distal of a diaphragm to iliofemoral junction. The aortoiliac
artery graft may comprise an aorta artery and one iliac artery. The
aortoiliac artery graft may comprise an aorta artery and two iliac
arteries.
[0009] The aortoiliac artery graft may further comprise at least
one renal artery. The aortoiliac artery graft may further comprise
two renal arteries. The aortoiliac artery graft may further
comprise an iliofemoral junction.
[0010] The aortoiliac artery graft may be decellularized and/or
devitalized. The aortoiliac artery graft may be plasticized using a
solution comprising glycerol at a concentration in the range of
35-60% by volume.
[0011] A method of processing an aortoiliac artery graft is also
provided. The processing method comprises subjecting an aortoiliac
artery to a pressure ex vivo, and determining a measured
pressurized diameter of the aortoiliac artery under the pressure.
As a result, a processed aortoiliac artery graft is obtained.
[0012] The pressure applied may be controlled by using a pressure
relief valve or a calibrated syringe. The measured pressurized
diameter may be determined by using a tool selected from the group
consisting of a ruler, a caliper, an umbilical tape, a laser
micrometer and ultrasound. The pressurized diameter may be a
measured pressurized outer diameter of the aortoiliac artery. The
pressurized diameter may be a measured pressurized inner diameter
of the aortoiliac artery.
[0013] The processing method may further comprise determining a
measured unpressurized diameter of the aortoiliac artery. The
measured unpressurized diameter may be a measured unpressurized
outer diameter of the aortoiliac artery. The measured unpressurized
diameter may be a measured unpressurized inner diameter of the
aortoiliac artery.
[0014] The processing method may further comprise releasing the
pressure from the aortoiliac artery. The processing method may
further comprise isolating the aortoiliac artery from a donor.
[0015] According to the processing method, the aortoiliac artery
graft may be decellularized and/or devitalized. The aortoiliac
artery graft may be plasticized using a solution comprising
glycerol at a concentration in the range of 35-60% by volume.
[0016] According to each processing method, a processed aortoiliac
artery graft is prepared.
[0017] A method of treating abdominal aortic aneurysm, infected
aortoiliac endograft or a traumatically damaged abdominal aorta or
an iliac artery in a patient is further provided. The treatment
method comprises anastomosing a processed aortoiliac artery graft
with an aorta of the patient on the proximal end and the iliac or
femoral arteries on the distal end. A measured pressurized diameter
of the processed aortoiliac artery graft has been determined ex
vivo under a pressure.
[0018] The treatment method may further comprise matching the
measured pressurized diameter of the processed aortoiliac artery
graft with a diameter measurement of the aorta of the patient
before the anastomosing step.
[0019] According to the treatment method, the measured pressurized
diameter of the processed aortoiliac artery graft may be within
90-110% of the diameter measurement of the aorta of the patient.
The measured pressurized diameter of the processed aortoiliac
artery graft may be a measured pressurized outer diameter of the
processed aortoiliac artery graft, the diameter measurement of the
aorta is an inner diameter measurement of the aorta, and the
measured pressurized outer diameter of the processed aortoiliac
artery graft is within 97-103% of the inner diameter measurement of
the aorta. The processed aortoiliac artery graft may be prepared
according to the method of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] FIG. 1 shows a processed human aortoiliac artery (AI) graft
including figure-of-eight mattress ligations. The graft is shown
with male barbed Luer attachments used to cannulate both the iliac
branches for connection to the pressurization testing model.
[0021] FIG. 2 shows a digital manometer and other components of a
pressurization testing setup, including a tubing y-connector, a
3-way stopcock, and a drain tube.
[0022] FIG. 3 shows a full pressurization testing assembly for an
AI model.
[0023] FIG. 4 shows a full pressurization testing assembly for a
synthetic elastomer vessel model.
[0024] FIG. 5 shows components of a PRV benchtop testing apparatus.
A 60 cc syringe is loaded in a syringe pump and connected to a
tubing circuit, which includes a 3D-printed vessel. The vessel is
cannulated at the distal end and attached to a hemostasis port to
allow catheterization of the vessel with a pressure-sensing
catheter.
[0025] FIG. 6 shows a processed human AI graft including
figure-of-eight mattress ligations, with barbed Luer attachments
used to cannulate both the iliac branches for connection to PRV and
catheter access port (top left panel); a processed human AI graft
depicted in a configuration to be used in clinical processing, with
a PRV, a check valve, and a 60 cc syringe attached at an iliac and
clamped at proximal aortic end (where the top iliac artery would be
simply ligated without a barb, however) (bottom panel); and an
expanded view of the PRV and other components used in the assembly
(top right panel).
[0026] FIG. 7 shows components of a setup for a validation section
of testing. An AI graft depicted in the configuration to be used in
clinical processing, with PRV, check valve, and 60 cc syringe
attached at an iliac and clamped at proximal aortic end. The other
iliac artery will be used to advance a pressure-sensing catheter
into the lumen of the graft.
[0027] FIG. 8 shows pressurization of AIs with PRVs with a plot of
pressure vs. time generated from pressurization of three different
AIs with PRVs from the indicated lots. Data were recorded using a
pressure-sensing catheter and LabView software. The pressures in
the 60-second period following valve opening (the first pressure
peak) were analyzed to see if the PRV could enable maintenance of
stable pressure.
[0028] FIGS. 9A-F show different configurations of AI grafts.
[0029] FIGS. 10A-B show exemplary labels.
DETAILED DESCRIPTION OF THE INVENTION
[0030] The present invention provides a reliable and accurate
diameter measurement for an AI graft under a pressure, for example,
similar to physiological arterial pressure permitting a more
precise and accurate match with a patient's aorta measurement
obtained from MRI or CT. In particular, the AI grafts of present
invention are provided with measured pressurized diameters, for
example, pressurized inner and/or outer diameters.
[0031] In surgery to remove an infected previously implanted graft
from a patient, the patient's aorta is typically cross clamped to
stop blood flow before removing it. The surgeon knows the patient's
aorta diameter, from pre-operative imaging, and would choose an AI
graft having the best size match with the patient's aorta. The
problem is that AI grafts from different donors in general have
flaccid (or unpressurized) diameters significantly different from
their corresponding pressurized diameters. The pressurized outer
diameters cannot be accurately predicted based on flaccid inner
diameters. For example, for donors with an 11 mm flaccid (or
unpressurized) inner diameter (ID) aorta, an AI graft from one
donor may have a distended (or pressurized) outer diameter (OD) of
15 mm while an AI graft from another donor may have a distended (or
pressurized) OD of 21 mm. Thus, there are significant differences
in distended (or pressurized) ODs among AI grafts from different
donors having the same flaccid (or unpressurized) ID and the
pressurized ID/OD cannot be accurately or reliably predicted from
the flaccid ID. As soon as the aorta cross clamp is released, this
difference in pressurized diameter (e.g., pressurized ID or OD)
will be observed. If the difference is too great (e.g., more than
20, 30, 40, 50, 60, 70% different from the patient's aorta
diameter), this is called a patient mismatch. Then, the surgeon
needs to modify either the graft, the patient's aorta or in the
instance of a gross mismatch modify both the patient's aorta and
the graft to get the diameters to match more closely to avoid
excessive turbulent blood flow. According to the invention, the
best way to avoid patent mismatch is to measure and report the
pressurized ID or OD of the AI graft when processing it. This is a
major advantage of the present invention.
[0032] The term "aortoiliac artery (AI) graft" as used herein
refers to the portion of aortoiliac artery (AI) isolated from a
donor beginning distal to the diaphragm and ending at the
iliofemoral junction. The donor may be a mammal, preferably a
human. The AI grafts may have different configurations to serve
patients with varying pathology and anatomy (FIGS. 10A-F).
[0033] The term "processing" as used herein refers to a method of
preparing the AI graft by treatment of the isolated AI graft before
clinical use. The processing may include dissection, determination
of the configurations and/or sizes of the AI graft, disinfection
cryopreservation, decellularization or devitalization, preservation
and terminal sterilization.
[0034] The AI graft may comprise a full aortoiliac artery, an
abdominal aorta distal to renal arteries inclusive of iliac
arteries to an iliofemoral junction, or an abdominal aorta distal
of renal arteries and inclusive of at least 1 cm of an iliac
artery. The aortoiliac artery may comprise a distal aorta and
iliacs without renal arteries. The aortoiliac graft may comprise an
aorta distal of a diaphragm to iliofemoral junction.
[0035] The aortoiliac artery graft may comprise an aorta artery and
one or two iliac artery. The aortoiliac artery graft may further
comprise one or two renal artery. The aortoiliac artery graft may
further comprise an iliofemoral junction.
[0036] The aortoiliac artery graft may be decellularized. A
decellularization process may be performed after cutting of a
processed tissue material, for example, an aortoiliac artery graft,
without damage to matrix and/or tissue structure of the tissue
material and may employ detergents, dodecyl sulphates,
endonuclease, and decontaminating agents. The matrix structure may
include collagens, hyaluronins, elastins, mucopolysaccharides and
proteoglycans, among other components. In another aspect, the
processing described herein may also comprise sterilizing the
tissue material. Sterilization may involve the use of ionizing
radiation, in some examples. In other examples, the absorbed dose
of ionizing radiation may be between 8.0 KGy and 50 KGy, between
8.0 KGy and 25 KGy, or between 8.0 KGy and 18 KGy. In some
examples, the sterilizing step may include placing a packaged graft
on dry ice and irradiating the packaged product. In certain
examples, sterilization may be performed at a temperature of
between -20.degree. C. and -50.degree. C. The processed tissue
material described herein may be sterilized using gamma
irradiation, supercritical carbon dioxide, ethylene oxide, or
electronic-beam.
[0037] The aortoiliac artery graft may be devitalized. A
devitalization process may be performed after cutting of the
processed tissue material, for example, an aortoiliac artery graft,
without damage to matrix and/or tissue structure of the tissue
material and may employ detergents, sarcosinates, endonuclease, and
decontaminating agents. The matrix structure may include collagens,
hyaluronins, elastins, mucopolysaccharides and proteoglycans, among
other components. In another aspect, the processing described
herein may also comprise sterilizing the tissue material.
Sterilization may involve the use of ionizing radiation, in some
examples. In other examples, the absorbed dose of ionizing
radiation may be between 8.0 KGy and 50 KGy, between 8.0 KGy and 25
KGy, or between 8.0 KGy and 18 KGy. In some examples, the
sterilizing step may include placing a packaged graft on dry ice
and irradiating the packaged product. In certain examples,
sterilization may be performed at a temperature of between
-20.degree. C. and -50.degree. C. The processed tissue material
described herein may be sterilized using gamma irradiation,
supercritical carbon dioxide, ethylene oxide, or
electronic-beam.
[0038] The aortoiliac artery graft may be plasticized using a
solution comprising glycerol at a concentration in the range of,
for example, about 20-80%, 15-75%, 30-70%, 20-60%, 35-60%, 40-60%,
45-60% or 50-55% by volume. The glycerol concentration may be about
55% by volume. The plasticization processing described herein may
further comprise treating the tissue material, for example, an
aortoiliac artery graft, with a water-replacing agent. The water
replacing agent may comprise one or more selected from the group
consisting of glycerol (glycerin USP), adonitol, sorbitol, ribitol,
galactitol, D-galactose, 1,3-dihydroxypropanol, ethylene glycol,
triethylene glycol, propylene glycol, glucose, sucrose, mannitol,
xylitol, meso-erythritol, adipic acid, proline, hydroxyproline,
polyethylene glycol, alcohol, and lipids. The processing described
herein may further comprise plasticizing the tissue material
according to the teachings of one or more of U.S. Pat. Nos.
6,293,970, 6,569,200, 6,544,289, 7,063,726, or U.S. Patent
Application Publication Nos. 2010/0030340, 2014/0180437,
2011/0015757, and 2013/0218294, each of which is incorporated
herein by reference by its entirety.
[0039] A package is provided. The package comprises an aortoiliac
artery graft and a first record. The first record may provide a
measured pressurized diameter of the aortoiliac artery graft. The
measured pressurized diameter may be determined ex vivo during
processing under a pressure, for example, similar to an arterial
pressure permitting a more precise and accurate match with a
patient's aorta. The measured pressurized diameter may be a
measured pressurized outer diameter (also known as a distended
outer diameter) of the aortoiliac artery graft and may be
determined using a syringe with a 130-mmHg pressure relief valve
attached and methods of measurement common in the field. The
diameter may be measured at the most distal portion of the aorta
(FIG. 10). The measured pressurized diameter may be a measured
pressurized inner diameter of the aortoiliac artery graft and may
be determined using ultrasound. The first record may be a package
marking, label or package insert (FIG. 9).
[0040] The package may further comprise a second record. The second
record may provide a measured unpressurized diameter of the
aortoiliac artery graft (FIG. 10). The unpressurized diameter may
be determined ex vivo during processing. The measured unpressurized
diameter may be a measured unpressurized outer diameter of the
aortoiliac artery graft. The measured unpressurized diameter may be
a measured unpressurized inner diameter of the aortoiliac artery
graft. The measured unpressurized inner diameter (also known as
flaccid inner diameter) may be determined by using Hegar dilator.
Additionally, the outer unpressurized diameter may be obtained
while the Hegar dilator is in place using common measurement means
in the field. The second record may be a package marking, label or
package insert.
[0041] The applied pressure may be caused by liquid, gas or
mechanical pressure. In some embodiments, liquid pressure such as
hydrostatic pressure is preferred. The applied pressure may be in a
range of 70-170 mmHg, 100-160 mmHg, 110-150 mmHg, 120-140 mmHg,
125-135 mmHg or around 130 mmHg.
[0042] A method of processing an aortoiliac artery graft is
provided. The processing method comprises subjecting an aortoiliac
artery to a physiological pressure ex vivo during processing, and
determining a measured pressurized diameter of the aortoiliac
artery under the physiological pressure. As a result, a processed
aortoiliac artery graft pressurized diameter is obtained. The
pressure may be controlled by using a pressure relief valve or a
calibrated syringe. The measured pressurized diameter may be
determined by using a tool selected from the group consisting of,
but not limited to, a ruler, a caliper, an umbilical tape, a laser
micrometer and ultrasound. The pressurized diameter may be a
measured pressurized outer diameter of the aortoiliac artery. The
pressurized diameter may be a measured pressurized inner diameter
of the aortoiliac artery.
[0043] The processing method may further comprise determining a
measured unpressurized diameter of the aortoiliac artery. The
measured unpressurized diameter may be a measured unpressurized
outer diameter of the aortoiliac artery. The measured unpressurized
diameter may be a measured unpressurized inner diameter of the
aortoiliac artery. The measured unpressurized diameter may be
determined by using a tool selected from the group consisting of,
but not limited to, a ruler, a caliper, an umbilical tape, a laser
micrometer and ultrasound.
[0044] The processing method may further comprise isolating the
aortoiliac artery from a donor. The donor may be a mammal,
preferably a human.
[0045] The processing method may further comprise dissection,
disinfection, cryopreservation, decellularization, devitalization,
plasticization, packaging and/or terminal sterilization in addition
to pressurizing the artery, measuring the ID/OD and subsequently
releasing the pressure from the aortoiliac artery.
[0046] For each processing method, a resulting processed aortoiliac
artery graft is provided.
[0047] A method of treating abdominal aortic aneurysm, infected
aortoiliac endograft or a traumatically damaged abdominal aorta or
iliac arteries in a patient is provided. The treatment method
comprises anastomosing a processed aortoiliac artery graft with an
aorta of the patient on the proximal end and the iliac or femoral
arteries on the distal end. A measured pressurized diameter of the
processed aortoiliac artery graft may be determined ex vivo under a
pressure.
[0048] The treatment method may further comprise matching the
measured pressurized diameter of the processed aortoiliac artery
graft with a diameter measurement of the aorta of the patient
before the anastomosing step. The diameter measurement of the aorta
of the patient may be obtained by a CT scan, for example, a CT
contrast scan.
[0049] According to the treatment method of the present invention,
the measured pressurized diameter of the processed aortoiliac
artery graft may be within 80-120%, 85-115%, 90-110%, 95-105%,
97-103% or 99-101% of the diameter measurement of the aorta of the
patient. In one embodiment, the measured pressurized diameter of
the processed aortoiliac artery graft is a measured pressurized
outer diameter of the processed aortoiliac artery graft, the
diameter measurement of the aorta is an inner diameter measurement
of the aorta, and the measured pressurized outer diameter of the
processed aortoiliac artery graft is within 80-120%, 85-115%,
90-110%, 95-105%, 97-103% or 99-101% of the inner diameter
measurement of the aorta.
[0050] The term "about" as used herein when referring to a
measurable value such as an amount, a percentage, and the like, is
meant to encompass variations of .+-.20% or .+-.10%, .+-.5%,
.+-.1%, or .+-.0.1% from the specified value, as such variations
are appropriate.
Example 1. Diameter Measurements of Aortoiliac Artery Grafts
[0051] The flaccid inner diameters (ID) and distended outer
diameters (OD) of 16 clinical aortoiliac artery (AI) grafts (Table
1) and 49 developmental aortoiliac artery (AI) grafts (Table 2)
were determined. The AI grafts were prepared for measurement by
cleaning of adipose tissue. All arteries were ligated with prolene.
The aorta was clamped. A cannula was ligated to one of the iliac
arteries. A calibrated Medtronic 125 mm Hg syringe was filled with
isotonic saline and the graft inflated for the OD measurement,
which was taken with a ruler. The distended OD was obtained using
the calibrated Medtronic 125 mm Hg syringe and inflating to a
target pressure of 125 mm Hg. The ligations were removed and the
flaccid ID was obtained using Hegar dilators. The mean and standard
(std) are of the percent change column.
TABLE-US-00001 TABLE 1 Clinical Grafts Code Flaccid ID (mm) Dist OD
(mm) % Mean Std DAI1016 10 16 38% DAI1016 10 16 38% AI1017 10 17
41% AI1020 10 20 50% 42% 6% DAI1115 11 15 27% DAI1116 11 16 31%
DAI1116 11 16 31% DAI1117 11 17 35% AI1117 11 17 35% DAI1117 11 17
35% DAI1118 11 18 39% AI1118 11 18 39% AI1121 11 21 48% 36% 6%
ABA1218 12 18 33% AI1221 12 21 43% AI1221 12 21 43% 40% 5%
TABLE-US-00002 TABLE 2 Developmental Grafts Flaccid ID (mm) Dist OD
(mm) % Mean Std 10 14 29% 10 15 33% 10 16 38% 10 16 38% 10 18 44%
36% 6% 11 13 15% 11 15 27% 11 16 31% 11 16 31% 11 16 31% 11 17 35%
11 17 35% 11 17 35% 11 18 39% 11 18 39% 11 19 42% 33% 7% 12 16 25%
12 17 29% 12 17 29% 12 18 33% 12 18 33% 12 18 33% 12 18 33% 12 18
33% 12 18 33% 12 18 33% 12 19 37% 12 19 37% 12 19 37% 12 20 40% 12
20 40% 12 21 43% 34% 4% 13 15 13% 13 16 19% 13 16 19% 13 18 28% 13
19 32% 13 19 32% 13 22 41% 13 22 41% 28% 10% 14 18 22% 14 18 22% 14
20 30% 14 20 30% 14 21 33% 14 22 36% 29% 6% 16 21 24% 16 22 27% 17
22 23% 25% 2%
Example 2. Additional Embodiments
[0052] Additional embodiments according to the present invention
are shown in FIGS. 1-8.
[0053] Some definitions are set forth below:
[0054] 1. BacT/Alert (BTA) bottles: Bottles used to collect and
incubate microbial (Aerobic and Anaerobic) samples for testing in
the Bac-T-Alert system.
[0055] 2. Cold pack: Frozen block/ice substitute used to maintain
the dissection solution temperature within a range of 1-10.degree.
C. during the processing procedure.
[0056] 3. Microbiological Samples: Refers to the Processing
Representative sample (PRS) and Representative Sample (RS).
[0057] 4. Processing Filter (PF): A 0.2 micron filter used to
filter the last rinse solution. The filter is plated and used for
microbial testing.
[0058] 5. Processing Representative Sample (PRS): A 1 cm.times.1 cm
sample piece of tissue co-processed with the tissue intended for
transplant. It is considered "processing" as it is never exposed to
disinfection solution.
[0059] 6. Representative Sample (RS): A 1 cm.times.1 cm sample
piece of tissue co-processed with the tissue intended for
transplant through final packaging.
[0060] 7. CV disinfection solution: Combination of antibiotics and
RPMI used to disinfect CV tissue. Refer to MP-10-021 for
preparation procedure.
[0061] 8. Meropenem: The diluted 2.5 ml dose of Meropenem prepared
according to instructions in MP-10-021.
[0062] 9. Eraxis: The diluted 2.5 ml dose of Eraxis (Anidulafugin)
prepared according to instructions in MP-10-021.
[0063] 10. Suture Ligature: A strand of suture material attached to
a needle to ligate a vessel, duct or other structure. The needle is
passed through the structure, or adjacent tissue first to anchor
the suture, then tied around the structure.
[0064] 11. F8: Refers to a specific type of suture ligature
technique, the figure-of-eight mattress ligature
[0065] 12. Major arterial branches: Arteries that depart from the
aorta to supply blood to major organs and or structures (e.g.,
celiac, superior and inferior mesenteric, and renal).
[0066] 13. Minor arterial branches: All other branches that are not
considered by definition as major arterial branches.
[0067] 14. TOD: Time of Death.
[0068] For aortoiliac artery graft sizing, the dimensions of the
graft are measured as follows:
[0069] 1. Aorta flaccid diameter (AFD): Measure in mm, inner
diameter (ID) of the flaccid aorta with a Hegar dilator where the
OD measurement was obtained so they are relatable. To measure, wet
the dilator and slide it into the aorta. The appropriate dimension
sizer should slide into the artery without any pressure inside the
vessel and without leaving gaps or dilation of the arterial wall.
This technique is analogous to that used to obtain the annulus
measurement for a heart valve.
[0070] 2. Aorta length (AL): Measure, in cm, the flaccid aorta from
the proximal end of the aorta to saddle region of the common
R&L iliac arteries.
[0071] 3. Iliac arteries, right (RIA) and left (LIA): Measure, in
cm, flaccid iliac arteries from the origin at the aorta to distal
end of the right and left iliac arteries.
[0072] 4. Major arterial branches (celiac trunk, superior
mesenteric artery and renal arteries): Measure in cm, flaccid
conditions. Minimum acceptable length is 0.5 cm when measured from
the aorta distally to the end of the artery.
[0073] 5. Total Flaccid Length (TFL): Measure in cm, under flaccid
conditions, from the proximal end of the aorta to the distal end of
the shortest iliac artery.
[0074] The setup with the PRV is similar in FIGS. 7 and 8. The
pressurized ID is obtained by inflating vessel with normal saline.
A high frequency (7-10-MHz) ultrasound transducer is used, which
allows higher spatial resolution to obtain a highly accurate +/-3%
pressurized ID. B-mode US is used because it provides high
resolution image of the lumen of the AI. In one example,
cross-sectional images are obtained perpendicular to the aorta at
the most proximal portion of the aorta, the line drawing tool is
selected, a line is drawn connecting the opposing lumen walls and
the ID is displayed on the screen. This is repeated two more times,
and then the three lengths are averaged and reported.
Example 3. Decellularization Processing of Arteries
[0075] The main goal of this study was to further optimize arterial
decellularization process to produce more robust decellularization
while maintaining matrix integrity of arteria grafts. One objective
was to reduce the preservation step's glycerol concentration from
77% glycerol and assess the degree to which various reduced
glycerol concentrations (15%, 30%, 45%, 60%) protect the matrix
from either compaction or damage during processing, freezing, and
gamma irradiation.
[0076] An investigation of various glycerol concentrations was
performed because higher concentrations increase intraluminal
pressure generation (and therefore require limiting flow rate to
avoid damage from over pressurization), but lower concentrations
contain too much water, which could result in freezing artifacts
and/or free radical-induced damage from irradiation. Consequently,
the study intended to identify a glycerol concentration that
provided a balance between increasing flow rate to improve the
robustness of decellularization and maintaining matrix integrity
during processing, freezing, and gamma irradiation.
[0077] The residual DNA acceptance criterion was met and
decellularization was achieved for all treatment groups.
Additionally, differential scanning calorimetry did not indicate
significant matrix damage nor any differences between glycerol
concentrations. Histological assessment showed that 15% glycerol
did not protect the arterial matrix, as an unacceptable number of
gaps between the collagen and elastin in the extracellular matrix
were visible. It was also determined that 30% glycerol was
borderline acceptable for matrix integrity based upon histological
review. Both 45% and 60% glycerol protected matrix integrity during
freezing and gamma irradiation without compaction. Finally, 77%
glycerol produced unacceptable matrix compaction that could
potentially hinder length and compaction recovery upon dilution.
Mercury intrusion and hemocompatibility testing did not demonstrate
statistically significant differences between groups.
[0078] Overall, the data suggest that reducing glycerol
concentration while increasing process flow rate is a viable
approach to improving robustness of decellularization for arterial
tissues. Results suggest the acceptable range of glycerol
concentrations for preserving matrix integrity range from 30%-60%,
with 30% still potentially questionable in that regard.
[0079] All documents, books, manuals, papers, patents, published
patent applications, guides, abstracts, and/or other references
cited herein are incorporated by reference in their entirety. Other
embodiments of the invention will be apparent to those skilled in
the art from consideration of the specification and practice of the
invention disclosed herein. It is intended that the specification
and examples be considered as exemplary only, with the true scope
and spirit of the invention being indicated by the following
claims.
* * * * *