U.S. patent application number 13/929606 was filed with the patent office on 2013-10-31 for biological tissue for surgical implantation.
The applicant listed for this patent is Edwards Lifesciences Corporation. Invention is credited to James A. Davidson, Bin Tian.
Application Number | 20130289695 13/929606 |
Document ID | / |
Family ID | 39327061 |
Filed Date | 2013-10-31 |
United States Patent
Application |
20130289695 |
Kind Code |
A1 |
Tian; Bin ; et al. |
October 31, 2013 |
BIOLOGICAL TISSUE FOR SURGICAL IMPLANTATION
Abstract
A method of treating a biological tissue that enables dry
storage of said tissue is disclosed. In one embodiment, the method
comprises contacting the biological tissue with a non-aqueous
treatment solution comprising a polyhydric alcohol and a
C.sub.1-C.sub.3 alcohol and removing a portion of the treatment
solution from the solution-treated biological tissue. Also
disclosed is biological tissue prepared using the above process and
prosthetic devices made with such tissue.
Inventors: |
Tian; Bin; (Irvine, CA)
; Davidson; James A.; (San Juan Capistrano, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Edwards Lifesciences Corporation |
Irvine |
CA |
US |
|
|
Family ID: |
39327061 |
Appl. No.: |
13/929606 |
Filed: |
June 27, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13189036 |
Jul 22, 2011 |
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13929606 |
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11877548 |
Oct 23, 2007 |
8007992 |
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13189036 |
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60854938 |
Oct 27, 2006 |
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Current U.S.
Class: |
623/1.11 ;
623/1.13 |
Current CPC
Class: |
A61L 27/3604 20130101;
A61L 27/3687 20130101; A01N 1/0215 20130101; A61L 27/507 20130101;
A61L 2430/40 20130101; A61F 2/2415 20130101 |
Class at
Publication: |
623/1.11 ;
623/1.13 |
International
Class: |
A61F 2/24 20060101
A61F002/24 |
Claims
1. A method of manufacturing a bioprosthetic heart valve
comprising: providing a biological tissue and a stent; contacting
the biological tissue with a treatment solution comprising a
polyhydric alcohol and an alcohol that is different from the
polyhydric alcohol; mounting the biological tissue to the stent to
produce a bioprosthetic heart valve; wherein the biological tissue
remains pliable following the contacting; and wherein the
contacting is performed either before or after the mounting.
2. The method of claim 1, wherein the stent is elastic.
3. The method of claim 2, wherein the bioprosthetic heart valve is
collapsible.
4. The method of claim 1, further comprising fixing the biological
tissue prior to the contacting.
5. The method of claim 1, further comprising decellularizing the
biological tissue prior to the contacting.
6. The method of claim 4, wherein the fixing is performed in the
presence of glutaraldehyde.
7. The method of claim 1, wherein the polyhydric alcohol is one or
a combination selected from the group consisting of: glycerol,
propylene glycol, a derivative of glycerol, and a derivative of
propylene glycol.
8. The method of claim 1, wherein the polyhydric alcohol comprises
one or a combination of a C.sub.1-C.sub.3 alcohol.
9. The method of claim 1, further comprising packaging the
bioprosthetic heart valve in a container or package that does not
contain a liquid storage solution in contact with the bioprosthetic
heart valve.
10. The method of claim 9, further comprising applying a vacuum to
the packaging and backfilling the packaging with an inert gas.
11. The method of claim 9, further comprising sterilizing the
biological tissue by exposure to a gas or to ionizing
radiation.
12. The method of claim 11, wherein the sterilizing is performed
with ethylene oxide gas.
13. The method of claim 1, wherein the contacting is performed
before the mounting.
14. The method of claim 1, wherein the contacting is performed
after the mounting.
Description
RELATED APPLICATIONS
[0001] The present application is a continuation of U.S.
application Ser. No. 13/189,036, filed Jul. 22, 2011, which is a
divisional of U.S. application Ser. No. 11/877,548, filed Oct. 23,
2007, now U.S. Pat. No. 8,007,992, which claims priority under 35
U.S.C. .sctn.119(e) to U.S. Provisional Application No. 60/854,938,
filed Oct. 27, 2006.
FIELD OF INVENTION
[0002] The invention is directed to the preparation or storage of
biological tissues used for surgical implantation. The invention is
also directed to biological tissues and bioprosthetic devices
containing such tissues.
BACKGROUND OF THE INVENTION
[0003] Animal tissue that is often used in implantable
bioprosthetic devices or to repair damaged tissue in a patient is
typically provided to medical personnel stored with or previously
treated with chemical agents such as formaldehyde and/or
glutaraldehyde. This chemical treatment helps to prevent rejection
of the implanted bioprosthetic device by the recipient, provides
for sterilization and helps to stabilize the proteins in the
tissue, thereby making the tissue or device containing such tissue
more resistant to mechanical fatigue and degradation by proteolytic
enzymes. Formaldehyde and glutaraldehyde, for example, stabilize
the tissue by forming cross-links with collagen and other proteins
in the tissue. Also, the tissue is often stored in a dilute aqueous
solution containing glutaraldehyde (and/or formaldehyde) to
maintain the tissue components in a hydrated state and to maintain
a microbe-free environment. However, tissue containing these agents
must be extensively rinsed prior to surgical implantation.
Moreover, an important consideration in selecting a biological
tissue for implantation is that the tissue should be readily
available to medical personnel in as close to a ready-to-use form
as possible, that is, with minimal preparation prior to surgery.
This reduces the opportunities for error and also the implantation
time.
[0004] Attempts have been made to develop procedures to pre-treat
biological tissue and bioprosthetic devices containing biological
tissue so that such tissue and devices can be provided to medical
personnel substantially free of formaldehyde or glutaraldehyde, and
to provide the biological tissue in a substantially dry form that
is ready for implantation or rehydration. One attempt to address
this issue involved immersing the biological tissue in aqueous
C.sub.1-C.sub.3 alcohol, for example aqueous ethanol solutions,
see, U.S. Pat. Nos. 6,277,555 and 6,630,001 to Duran et al. The
solution treated tissue is then immersed in an aqueous glycerol
solution or low molecular weight (<1000 D) polyethylene glycol.
Thereafter, the tissue is briefly immersed in aqueous heparin
solution, frozen and lyophilized.
[0005] U.S. Pat. No. 4,300,243 describes the preparation of
biological collagenous tissue for surgical implantation. The
preparation of the tissue includes contacting the tissue with fresh
amounts of a water-miscible organic solvent selected from the group
consisting of methanol, ethanol, propanol, isopropanol, acetone,
methylethylketone and mixtures thereof. The excess alcohol is then
removed at a pressure of between 0.1 bar to 1.0 bar. However, it is
known that such dehydration processes significantly reduce the
overall dimensions of the tissue, that is, the tissue shrinks.
Also, biological tissue subject to this dehydration process cannot
be successfully rehydrated and returned to substantially its
original dimensions. As a result, bioprosthetic devices comprising
tissue components that have undergone such a dehydration process
are not good candidates for implantation. See, U.S. Pat. No.
6,534,004, col. 1, lines 53-65.
[0006] U.S. Pat. No. 6,534,004 describes a process of providing
bioprosthetic devices containing a biological tissue for dry
storage. The process includes treating the biological tissue with
an aqueous solution of organic compounds having a plurality of
hydroxyl groups (e.g., polyhydric alcohols, polyglycols or water
soluble carbohydrates). One of the more preferred treatment
solutions is an aqueous solution of glycerol or derivatives of
glycerol. The biological tissue is immersed in this solution,
removed and permitted to dry in air. The tissue is then sterilized
and packaged for storage.
[0007] All the foregoing prior art approaches to preparing tissue
for dry storage require the use of aqueous solutions. However, the
use of aqueous solutions makes the tissue susceptible to microbial
contamination. It is desirable, therefore, to totally eliminate
water from the process and to thus render the dried tissue less
prone to microbes. The present invention provides such a process.
It provides new methods for preparing biological tissue or
bioprosthetic devices containing such tissue suitable for sterile
dry storage, and available to medical personnel in as close to
ready-to-use form as possible.
SUMMARY OF THE INVENTION
[0008] A method of treating a biological tissue that enables dry
storage of said tissue is disclosed. In one embodiment, the method
comprises contacting the biological tissue with a non-aqueous
treatment solution comprising a polyhydric alcohol and a
C.sub.1-C.sub.3 alcohol and removing a portion of the treatment
solution from the solution-treated biological tissue. The
polyhydric alcohol concentration can be 40-95% and the
C.sub.1-C.sub.3 alcohol concentration can be 5-60% by volume. The
time of contact between the tissue and treatment solution can be
varied to control the treatment process. For example, in some
embodiments, the step of contacting the biological tissue with the
treatment solution is performed for a time of greater than 30
minutes.
[0009] In some embodiment, the polyhydric alcohol is glycerol and
the C.sub.1-C.sub.3 alcohol is selected from the group consisting
of ethanol, n-propanol, 2-propanol or a mixture thereof.
[0010] The biological tissue to be treated can be mammalian tissue,
for example, a tissue selected from the group consisting of
pericardium, aortic and pulmonary roots and valves, tendons,
ligaments, skin, dura, peritonium, blood vessels, pleura, diameter,
mitral and tricuspid valves.
[0011] In one embodiment, the treatment method further comprises
placing the biological tissue ready for sterilized containment in a
package form, wherein the package form is pre-sterilized or
sterilized following the placement of the tissue in the package
form, and sealing the package form.
[0012] Also disclosed herein is a sealed package containing a
sterilized solution-treated, biological tissue for surgical
implantation into a human, wherein the solution-treated, biological
tissue is prepared by one of the embodiments of the above-described
treatment process. Further, a sterilized solution-treated,
biological tissue for surgical implantation into a human is
disclosed wherein the sterilized, solution-treated biological
tissue prepared by one of the embodiments of the above-described
treatment process. Also disclosed is a heart valve prosthesis that
comprises a collapsible, elastic valve member, wherein the valve
member comprises a biological tissue that is solution-treated,
using one of the embodiments of the above-described treatment
process, an elastic stent member in which the valve member is
mounted, the stent member having internal and external surfaces and
a support coupled to the valve member and positioned between the
valve member and the stent member, wherein the stent member forms a
continuous surface and comprises strut members that provide a
structure sufficiently rigid to prevent eversion, and the support
extends from the internal surface of the stent member to the
external surface of the stent member, and wherein the stent member
has sufficient radial and longitudinal rigidity to withstand the
radial force necessary for implantation, to resist aortic recoil
forces, and to provide long-term support to the valve prosthesis.
In one embodiment, the heart valve prosthesis is provided in
sterilized form and ready for surgical implantation.
DETAILED DESCRIPTION OF THE DRAWING
[0013] No figures are provided.
DETAILED DESCRIPTION OF THE INVENTION
[0014] The invention is directed to a method of treating a
biological tissue of a mammal for preparation or storage. Ideally,
the method provides biological tissue or bioprosthetic devices
containing such tissue ready for surgical implantation, or for
rehydration, e.g., with physiologic saline. One embodiment of the
invention utilizes a non-aqueous combination of a polyhydric
alcohol and a C.sub.1-C.sub.3 alcohol. The method comprises
contacting the biological tissue with a treatment solution
comprising greater than 35% by volume of a polyhydric alcohol and
the balance of a C.sub.1-C.sub.3 alcohol. The treatment solution
contains no water, i.e., it is non-aqueous. For tissue that is
stored in a sterile storage solution for example a fixative
solution, contact of the biological tissue with the treatment
solution, e.g., by immersing the tissue in the solution, is
maintained for a time sufficient to exchange a substantial portion
of the pre-storage fluid, which may be aqueous, within the
interstitial volume of the tissue with the treatment solution. The
method also includes removing a portion of the treatment solution
from the solution-treated tissue to provide a biological tissue
ready for sterilized containment.
[0015] As used herein, a "polyhydric alcohol" is an organic
molecule that contains a plurality of carbon atoms and two or more
hydroxyl groups, wherein the hydroxyl groups are attached to carbon
atoms. Exemplary polyhydric alcohols include glycerol, ethylene
glycol, polyethylene glycols, propylene glycol, butylene glycol and
derivatives of glycerol. Two of the more preferred polyhydric
alcohols used in the process are glycerol and propylene glycol, and
derivatives of glycerol or propylene glycol. Of course, one or more
polyhydric alcohols in the form of a mixture can be used in the
process. Thus, it is to be understood that the term "a polyhydric
alcohol" is inclusive of a mixture of two or more polyhydric
alcohols. For example, a mixture of glycerol and propylene glycol
can be used in the process.
[0016] The biological tissue used in various embodiments of the
invention can be mammalian tissue, including human tissue, such as
tissue obtained from human donors or cadavers. Bovine, ovine,
equine, and porcine tissue can also be used. The types of tissue
used in these embodiments is the same tissue used in common
surgical procedures, and includes pericardium, aortic and pulmonary
roots and valves, tendons, ligaments, skin, peritoneum, facia,
pleura, mitral and tricuspid valves.
[0017] One of ordinary skill in the art would understand that the
treatment processes in accordance with some embodiments of the
invention can be practiced with fixed tissue or native tissue. In
some instances the biological tissue used in the process has been
previously fixed by treating the tissue with a fixative solution.
As used herein "fixed" tissue is one in which the proteins thereof
have reduced solubility, antigenicity, and biodegrading properties
as compared to the proteins in the native tissue. Typically, the
tissue is fixed by cross-linking the amine groups of the proteins
of the tissue with an aldehyde. The tissue fixation process can
include chemical and/or enzyme decellularization steps. The fixed
tissue is rinsed to substantially reduce the amount of unreacted
fixative within the tissue. In other instances, the biological
tissue is temporarily stored in a buffered saline solution prior to
the inventive treatment disclosed in this application.
[0018] The biological tissue is contacted with a treatment
solution, e.g., by immersing the tissue in the solution. In some
embodiments, the volume of the treatment solution is at least two
times, at least fifty times or at least one hundred times, the
volume of the biological tissue that is brought into contact with
the solution. If the biological tissue is to be attached to a
bioprosthetic device for implantation, the tissue can be treated
with the treatment solution prior to its attachment or after its
attachment to the bioprosthetic device. For example, bovine
pericardium can be treated with the treatment solution prior to the
time it is formed into a heart valve, vascular graft, stent
covering, or pericardial patch or after the bovine pericardium is
formed into a heart valve, vascular graft, stent covering, or
pericardial patch.
[0019] The C.sub.1-C.sub.3 alcohol is selected from the group
consisting of methanol, ethanol, isopropanol and n-propanol.
Ethanol is the preferred alcohol used in the process. Again, it is
to be understood that the term "a C.sub.1-C.sub.3 alcohol" is
inclusive of a mixture of two or more C.sub.1-C.sub.3 alcohols. For
example, a mixture of ethanol and isopropanol can be used in the
process.
[0020] The inventors have discovered that the concentration of the
polyhydric alcohol relative to the C.sub.1-C.sub.3 alcohol affects
the dimensional stability of the biological tissue during storage.
One other factor related to the dimensional stability of the tissue
is the type of tissue itself. For some biological tissue, the
treatment solution will comprise 70% to 95% by volume of a
polyhydric alcohol and 5% to 30% by volume of a C.sub.1-C.sub.3
alcohol. For example, applicants have determined that for bovine
pericardium heart valve the treatment solution will preferably
comprise 70% to 95% by volume of a polyhydric alcohol, and 5% to
30% by volume of a C.sub.1-C.sub.3 alcohol.
[0021] For tissue stored in a storage solution or fixative, by
contacting the biological tissue with the non-aqueous treatment
solution water is removed from the interstitial volume of the
tissue, rendering the tissue substantially dry.
[0022] Those skilled in the art will readily recognize that the
biological tissue can be contacted with the treatment solution in
one or more separate contacting steps. Instead of contacting the
tissue with the treatment solution in a single treatment step, the
contact step can be repeated one or more times using treatment
solutions of the same or similar concentrations of polyhydric
alcohol and C.sub.1-C.sub.3 alcohol. For example, two immersion
baths containing the same treatment solutions can be arranged. The
biological tissue containing a pre-storage fluid is immersed in the
first bath for a first time period. The tissue is then removed from
the first bath and immersed in the second bath for a second time
period. Of course, one of ordinary skill may determine that the
respective concentrations of the polyhydric alcohol and the
C.sub.1-C.sub.3 alcohol in each of the two baths are different, yet
within the stated and claimed amounts.
[0023] The time of contact between the biological tissue and the
treatment solutions is somewhat dependent on the thickness and type
of the tissue. As can be expected, with a relatively thick tissue
more time of contact is typically needed. Additionally, as is
well-known to a person of ordinary skill in the art, process
variables such as agitation, temperature, pressure, flow rate,
etc., will affect the needed time of contact.
[0024] The preparation of a polyhydric alcohol and C1-C3 alcohol
mixture (for example, a 75% -25% mixture) can take several hours
with stifling. The time needed to treat tissue with this solution
depends on many factors above mentioned and can take up to several
hours. In many cases, the process will involve maintaining
biological tissue with the treatment solution for eight hours or
more. In some instances, the time of exposure can exceed twelve,
sixteen or twenty-four hours.
[0025] Once the biological tissue has been sufficiently exposed to
the treatment solution, the tissue is removed from the solution and
exposed to ambient air or an inert environment, e.g., nitrogen, at
standard room temperature and humidity so as not to adversely
affect tissue properties (typically, at a temperature from about
15.degree. C. to about 25.degree. C., and relative humidity
preferably less than about 50%). Preferably, the drying is
performed in a clean room or in a laminar flow bench at ambient
room conditions for about 1-4 hours.
[0026] The treated and dried tissue or a bioprosthetic device
containing the treated and dried tissue is then packaged in a
container or package essentially free of liquid for subsequent
rehydration or implantation. A container or package that is
"essentially free of liquid" means a non-fluid environment in which
the presence of water or other substances is limited to
approximately the content of such substances in ambient air (as
more precisely defined by the relative humidity). The tissue or the
bioprosthetic device containing the tissue is placed into a
micro-organism resistant container or package. One preferred method
is to apply a vacuum to the package to minimize the level of
O.sub.2, and may additionally utilize a backfill of an inert gas,
such as nitrogen. Such methods of sterile packaging are known to
those skilled in the art. The packaged treated tissue can then be
sterilized by a gaseous sterilization process or by an exposure to
ionizing radiation including standard gamma and E-Beam methods. To
ensure that the chamber remains sterile following sterilization,
the package members are formed from a material that is impenetrable
to micro-organisms such as bacteria and fungi. After the tissue or
bioprosthetic device containing such tissue is placed in the
chamber and/or sterilized, the chamber is sealed.
[0027] Sterilization by exposure to ionizing radiation or
sterilizing gas, particularly by exposure to ethylene oxide, is
within the skill of the art. In a preferred embodiment, the tissue
is sterilized by exposing the tissue to gamma radiation. Examples
of conventional procedures for sterilization by exposure to
ethylene oxide involve exposure to 10% ethylene oxide and 90%
hydrochlorofluorocarbon at a chamber pressure of 8 to 10 psig at a
temperature of 38.degree. C. for 24 hours or at a temperature of
54-57.degree. C. for 130 minutes.
[0028] The resulting product is a substantially sterile and sealed
implantable tissue or bioprosthetic device containing such tissue
present in a substantially dry form. It is especially well-suited
for surgical implantation into human patients for the treatment of
any number of diseases or conditions. Prior to surgical
implantation, the biological tissue or bioprosthetic device
containing such tissue is removed from the package, and the tissue
component optionally rehydrated by exposure to an aqueous solution,
preferably a sterile aqueous solution. The tissue can be rehydrated
by multiple soakings in a sterile solution such as physiologic
saline. The glycerol in the tissue can be easily washed off by
saline. The majority of glycerol is eluted out by washing the
tissue in saline for about 3-5 minutes.
[0029] The described method of treating biological tissue and the
subsequent packaging of the tissue or device containing such tissue
eliminates the need to sterilize the tissue or the bioprosthetic
devices by medical personnel prior to surgical implantation. The
described method provides greater manufacturing control in
preparing tissue and bioprosthetic devices for surgical
implantation. In other words, the process of preparing the tissue
or prosthetic device for implantation need not occur at the
hospital or in the operating room. Again, the only step that may be
required of medical personnel is to rehydrate the tissue, or the
tissue on the bioprosthetic device, with physiologic saline or
other suitable rehydrating agents.
[0030] The described method provides a biological tissue or
bioprosthetic devices containing such tissue with dimensional
stability that is essentially ready for surgical implantation into
a patient. Biological tissue treated in accordance with the methods
described and claimed in this application will typically return to
a size that is at least about 97%, more preferably at least about
99% of its original hydrated size following dry storage for about
24 hours and rehydration in physiologic saline for about 5 minutes.
Accordingly, biological tissue prepared in accordance with the
described and claimed method are well-suited for use in an
implantable bioprosthetic device, and in particular, a
blood-contacting bioprosthetic device that is implanted into the
cardiovascular system of a patient.
[0031] An embodiment of the invention is also directed to a
bioprosthetic device that includes a pericardium tissue heart valve
processed by the methods described in this application. As
mentioned, the pericardium tissue can be processed according to the
described methods prior to or following its attachment to the
device. The heart valve has multiple leaflets joined together at a
periphery of the valve at valve commissures (a portion of the
holder) that are generally axially aligned and evenly disposed
about a valve axis. The valve commissures are each disposed between
adjacent curvilinear valve cusps along the periphery of the valve.
The bioprosthetic heart valve may further include a holder that
comprises a plurality of cusp supports arranged around an axis to
contact the heart valve generally along the valve cusps. The
pericardium heart valve attached to the holder is prepared and
treated by the method described in this application. A more
complete description of a bioprosthetic heart valve is described in
U.S. Pat. No. 5,928,281, which is assigned to Edwards Lifesciences,
the entire disclosure of which is incorporated into this
application by reference.
EXAMPLE 1
[0032] Bovine pericardium fixed in the presence of glutaraldehyde
is dissected to remove loose tissue and fat and sliced into discs
having a thickness and diameter as noted in Tables 1 and 2. The
dimensions of each disc are measured prior to treatment, and each
of the discs is immersed in the various treatment solution
compositions reported in Tables 1 and 2. The treatment solutions
are prepared approximately 16 hours prior to use of the solutions.
The tissue is immersed in each of the various solution compositions
at a solution: tissue volume ratio of 100:1. The tissue maintains
contact with the various treatment solutions for approximately 16
hours, after which the tissue is carefully removed from the
solution, excess liquid is allowed to drain from the tissue and the
tissue dried by air. The dimensions of each of the discs are again
measured. After 16 hours in the dried form, each of the discs is
rehydrated in normal saline. The rehydrated dimensions are again
measured.
TABLE-US-00001 TABLE 1 Composition 1 2 3 4 5 6 7 8 Glycerol (%) 100
90 80 70 60 50 40 30 Ethanol (%) 0 10 20 30 40 50 60 70 Tissue disc
diameter (mm) (Mean .+-. SD) Before 8.12 .+-. 0.06 8.26 .+-. 0.11
8.14 .+-. 0.07 8.14 .+-. 0.10 8.14 .+-. 0.08 8.20 .+-. 0.16 8.23
.+-. 0.11 8.2 .+-. 0.09 Treatment Treated 8.06 .+-. 0.04 8.12 .+-.
0.07 8.00 .+-. 0.05 8.02 .+-. 0.02 7.93 .+-. 0.03 7.81 .+-. 0.11
7.66 .+-. 0.09 7.25 .+-. 0.35 Dehydrated Treated 8.20 .+-. 0.23
8.23 .+-. 0.07 8.12 .+-. 0.06 8.14 .+-. 0.10 8.10 .+-. 0.10 8.11
.+-. 0.18 8.01 .+-. 0.11 7.89 .+-. 0.15 Rehydrated
TABLE-US-00002 TABLE 2 Composition 1 2 3 4 5 6 7 8 Glycerol (%) 100
90 80 70 60 50 40 30 Ethanol (%) 0 10 20 30 40 50 60 70 Tissue
thickness (mm) (Mean .+-. SD) Before 0.34 .+-. 0.02 0.36 .+-. 0.02
0.34 .+-. 0.05 0.38 .+-. 0.04 0.34 .+-. 0.05 0.34 .+-. 0.03 0.35
.+-. 0.06 0.38 .+-. 0.06 Treatment Glycerol 0.39 .+-. 0.04 0.36
.+-. 0.06 0.37 .+-. 0.06 0.38 .+-. 0.04 0.34 .+-. 0.07 0.34 .+-.
0.05 0.32 .+-. 0.04 0.32 .+-. 0.07 Treated Dehydrated Glycerol 0.35
.+-. 0.03 0.33 .+-. 0.05 0.34 .+-. 0.04 0.38 .+-. 0.04 0.34 .+-.
0.05 0.34 .+-. 0.04 0.32 .+-. 0.05 0.33 .+-. 0.06 Treated
Rehydrated
[0033] The treated and dried tissue is pliable and does not crack
or break by physical manipulations. It is rehydrated by immersion
in, for example, physiological buffered saline for approximately 5
minutes at ambient temperature. After rehydration, the tissue is
indistinguishable in appearance from the original (untreated) fixed
tissue.
[0034] As shown by the data of Tables 1 and 2, the tissue maintains
dimensional stability for all ranges of composition evaluated.
However, for more critical dimensional, considerations, e.g.
bioprosthetic heart valves, treatment solution compositional ranges
between about 50 to 95% glycerol, and the balance alcohol are
preferred.
[0035] Similar results were obtained from measurements of tissue
thickness following rehydration. In this case, there was no
observed difference in tissue thickness for those disks treated
with a solution at a volume ratio of glycerol:ethanol from 80:20 to
50:50.
[0036] Although various preferred embodiments of the present
invention have been disclosed for illustrative purposes, those
skilled in the art will appreciate that various modifications,
additions and/or substitutions are possible without departing from
the scope and spirit of the present invention as disclosed in the
claims.
* * * * *