# US 12,447,231 B2 · Human placental tissue graft products, methods, and apparatuses

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- Number: US 12,447,231 B2
- Document ID: US12447231B2
- Status: Granted
- Kind: B2
- Application number: 17/863,675
- Filed: 2022-07-13
- Published: 2023-03-23
- Granted: 2025-10-21
- Earliest claimed: 2016-01-08
- Assignees: Cryolife, Inc.
- Applicants: CryoLife, Inc.
- Inventors: Steven Goldstein; Adam Martinez; Candace Law
- Web page: https://patentgrep.com/patent/US12447231B2

## CPC

- 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 27/16: obtained by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/24: Collagen
- A61L 27/3695: {characterised by the function or physical properties of the final product, where no specific conditions are defined to achieve this (A61L27/3687, A61L27/3691 take precedence)}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/60: Materials for use in artificial skin
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- C12M 21/08: {for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00)}
- F26B 5/04: by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum {(F26B11/049 and F26B17/128 take precedence)}
- A61L 2300/236: Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
- A61L 2300/254: Enzymes, proenzymes
- A61L 2300/414: Growth factors
- A61L 2300/434: of enzymes
- A61L 2430/40: Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- F26B: DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM (drying devices for combines A01D41/133; racks for drying fruit or vegetables A01F25/12; drying foodstuffs A23; drying hair A45D20/00; body-drying implements A47K10/00; drying household articles A47L; drying gases or vapours B01D; chemical or physical processes for dewatering or like separating liquids from solids B01D43/00; centrifugal apparatus B04; drying ceramics C04B33/30; drying yarns or fabrics in association with some other form of treatment D06C; drying frames for laundry without heating or positive air circulation, domestic laundry-or spin-driers, wringing or hot pressing laundry D06F; furnaces, kilns, ovens F27)

## Abstract

Provided herein are tissue grafts, and in particular human placenta-derived tissue grafts and methods and articles for the manufacture and use thereof.

## Claims

### Claim 1

A method of producing a tissue graft, the method comprising:
removing decidua cells and trophoblast cells from a fetal support tissue membrane;
compressing the membrane;
dehydrating the membrane;
decontaminating the membrane; and
mounting the membrane to a: flexible backing material to produce a formed tissue graft;
wherein the native connective architecture between an amnion layer and a chorion layer of the membrane is maintained intact throughout the method,
wherein the amnion layer is not decellularized,
wherein the steps of compressing the membrane and dehydrating the membrane are performed simultaneously, and wherein the steps of compressing the membrane and dehydrating the membrane comprise positioning the membrane between a moisture-permeable support platform and a gas-impermeable sealing sheet, then depressurizing a chamber below the moisture-permeable support platform to pull a vacuum across the platform using a vacuum source,
wherein the chamber, being below the moisture-permeable support platform, defines an opening at one end, the chamber being in fluid connection with the vacuum source, and
wherein the moisture-permeable support platform covers the opening of the chamber and comprises a perforated rigid support layer and a moisture, liquid, and vapor permeable material layer, wherein the moisture, liquid, and vapor permeable material layer is positioned between the perforated rigid support layer and the membrane, and wherein the membrane is positioned between the gas-impermeable sealing sheet and the moisture, liquid, and vapor permeable material layer.

### Claim 2 (depends on 1)

The method of claim 1, further comprising retaining at least 10,000 pg/mg of native basic fibroblast growth factor (bFGF) from the membrane in the formed tissue graft.

### Claim 3 (depends on 1)

The method of claim 1, further comprising swelling the decidua cells and the trophoblast cells prior to removing the decidua cells and the trophoblast cells.

### Claim 4 (depends on 3)

The method of claim 3, wherein swelling the decidua cells and the trophoblast cells further comprises contacting a maternal side of the membrane with a hypotonic solution.

### Claim 5 (depends on 4)

The method of claim 4, wherein the decidua cells and the trophoblast cells are mechanically removed after swelling.

### Claim 6 (depends on 3)

The method of claim 3, wherein removing the decidua cells and the trophoblast cells from the membrane reduces the alloantigenicity to a Stimulation Index of less than 1 when measured by a peripheral blood mononuclear cell BrdU proliferation assay.

### Claim 7 (depends on 1)

The method of claim 1, wherein decontaminating the membrane comprises treating the membrane with buffered peracetic acid.

### Claim 8 (depends on 7)

The method of claim 7, wherein the concentration of buffered peracetic acid is from about 0.01% to about 1% v/v.

### Claim 9 (depends on 1)

The method of claim 1, wherein compressing the membrane further comprises applying a load to a surface of the membrane opposite the platform.

### Claim 10 (depends on 1)

The method of claim 1, wherein dehydrating the membrane further comprises flowing air through the chamber while the chamber is in a sealed state.

### Claim 11 (depends on 1)

The method of claim 1, wherein the moisture, liquid, and vapor permeable layer is a nonwoven or flashspun material.

### Claim 12 (depends on 1)

The method of claim 1, wherein the gas-impermeable sealing sheet comprises silicone.

### Claim 13 (depends on 1)

The method of claim 1, further comprising forming on the membrane a first, shiny surface adjacent to the gas-impermeable sealing sheet and a second, less shiny surface adjacent to the moisture, liquid, and vapor permeable layer.

### Claim 14 (depends on 1)

The method of claim 1, wherein dehydrating the membrane comprises sinking moisture from the membrane using a desiccant material.

### Claim 15 (depends on 1)

The method of claim 1, wherein mounting the membrane to a flexible backing material comprises releasably securing opposed ends of the membrane between two opposed tabs.

### Claim 16 (depends on 15)

The method of claim 15, wherein the flexible backing material is larger than the membrane.

### Claim 17 (depends on 1)

A method of using the tissue graft of claim 1, the method comprising storing the formed tissue graft at room temperature for at least six months and applying the formed tissue graft to a patient.