# US 12,083,009 B2 · Method of processing collagen-based tissue for bioprosthetic devices

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- Number: US 12,083,009 B2
- Document ID: US12083009B2
- Status: Granted
- Kind: B2
- Application number: 16/849,694
- Filed: 2020-04-15
- Published: 2021-10-21
- Granted: 2024-09-10
- Earliest claimed: 2020-04-15
- Assignees: Vitae LLC
- Applicants: Vitae LLC
- Inventors: Bin Tian
- Web page: https://patentgrep.com/patent/US12083009B2

## CPC

- A61F 2/2415: {Manufacturing methods}
- A61L 27/3604: {characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel}
- A61L 27/3625: {Vascular tissue, e.g. heart valves}
- A61L 27/3641: {characterised by the site of application in the body (materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60)}
- A61L 27/3687: {characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents}
- A61L 27/3691: {characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation}
- C12N 5/0657: {Cardiomyocytes; Heart cells}
- C12N 5/0697: {Artificial constructs associating cells of different lineages, e.g. tissue equivalents (blood vessels C12N5/0691)}
- A61L 2430/20: for reconstruction of the heart, e.g. heart valves
- A61L 2430/40: Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A method is provided for preparing pericardial tissue that is used for a bioprosthetic heart valve assembly. According to this method, pericardial tissue is harvested from a host animal and then cleaned. The cleaned tissue is then fixed using glutaraldehyde. After fixation of the tissue, the residual antigenic components are removed to preserve the tissue structural integrity for its long-term performance. In addition, higher concentrations of alcohol are used to reduce the tissue bioburden, and at the same time to dehydrate the tissue followed by preserving the tissue with glycerol so as to mitigate glutaraldehyde-storage related issues for the bioprosthetic heart valve.

## Claims

### Claim 1

A method for preparing a collagen-based pericardial tissue that is used for a bioprosthetic heart valve assembly, comprising:
a) harvesting a pericardial tissue from a host animal;
b) cleaning the harvested tissue;
c) fixing the cleaned tissue using glutaraldehyde;
d) treating the fixed tissue with a solution consisting of 20% to 70% alcohol and 0.1% to 1% polysorbate 20 in pH 7.0-7.5 buffered saline at 30° C. to 60° C., wherein the alcohol is either ethanol or isopropanol;
e) treating the treated tissue from the step d) with a 0.1% to 1.0% detergent solution containing one or more of the following detergents: sodium deoxycholate (SDC), sodium dodecyl sulfate (SDS), 3-[N,N-Dimethyl(3-myristoylaminopropyl)ammonio]propanesulfonate, amidosulfobetaine-14 (ASB-14), 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS); and
f) treating the treated tissue from the step e) using 65% to 75% alcohol, wherein the alcohol is either ethanol or isopropanol.

### Claim 2 (depends on 1)

The method of claim 1, wherein the detergent solution of the step e) is a combination of 0.5% of SDC and 0.25% ASB-14.

### Claim 3 (depends on 1)

The method for making a bioprosthetic heart valve assembly of claim 1, wherein the method further comprising:
g) cutting leaflets from the treated tissue of the step f) of claim 1;
h) assembling the heart valve assembly using the cut leaflets;
i) detoxifying the glutaraldehyde from the leaflets in the heart valve assembly;
j) dehydrating the leaflets in the heart valve assembly using 60% to 95% of alcohol for one to eight hours at 25° C. to 55° C., wherein the alcohol is either ethanol or isopropanol; and
k) treating the leaflets in the heart valve assembly with a solution consisting of 80-90% glycerol, 5-10% ethanol, and 3-10% deionized water at room temperature for 30 minutes to 24 hours.

### Claim 4 (depends on 1)

The method for making a bioprosthetic heart valve assembly of claim 1, wherein the method further comprising:
g) detoxifying the glutaraldehyde from the treated tissue from the step f) of claim 1;
h) dehydrating the tissue from the step g) using 60% to 95% of alcohol for one to eight hours at 25° C. to 55° C., wherein the alcohol is either ethanol or isopropanol;
i) treating the tissue from the step h) with a solution consisting of 80-90% glycerol, 5-10% ethanol, and 3-10% deionized water at room temperature for 30 minutes to 24 hours;
i) cutting leaflets from the treated tissue of the step i); and
k) assembling the heart valve assembly using the cut leaflets.