# US 11,077,231 B2 · Methods, substrates, and systems useful for cell seeding of medical grafts

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- Number: US 11,077,231 B2
- Document ID: US11077231B2
- Status: Granted
- Kind: B2
- Application number: 14/834,971
- Filed: 2015-08-25
- Published: 2015-12-17
- Granted: 2021-08-03
- Earliest claimed: 2010-05-25
- Assignees: Muffin Incorporated
- Applicants: Muffin Incorporated; Cook Biotech Incorporated
- Inventors: Michael C. Hiles; Chad E. Johnson; Neal E. Fearnot; Thomas Payne; Ronald Jankowski
- Web page: https://patentgrep.com/patent/US11077231B2

## CPC

- A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61L 27/24: Collagen
- 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 27/3633: {Extracellular matrix [ECM]}
- A61L 27/3808: {Endothelial cells}
- A61L 27/3826: {Muscle cells, e.g. smooth muscle cells}
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12M 21/08: {for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00)}
- C12M 23/06: {Tubular (C12M23/08, C12M23/16 take precedence)}
- C12M 23/34: {Internal compartments or partitions}
- C12M 25/14: {Scaffolds; Matrices (in general C12N5/0068)}
- C12N 5/0062: {General methods for three-dimensional culture}
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- A61L 2430/06: for cartilage reconstruction, e.g. meniscus
- A61L 2430/26: for kidney reconstruction
- A61L 2430/28: for liver reconstruction
- A61L 2430/30: for muscle reconstruction
- A61L 2430/32: for nerve reconstruction
- A61L 2430/34: for soft tissue reconstruction
- C12N 2533/54: Collagen; Gelatin
- 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}
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Described are methods, cell growth substrates, and devices that are useful in preparing cell-containing graft materials for administration to patients. Tubular passages can be defined in cell growth substrates to promote distribution of cells into the substrates. Also described are methods and devices for preparing cell-seeded graft compositions, methods and devices for preconditioning cell growth substrates prior to application of cells, and cell seeded grafts having novel substrates, and uses thereof.

## Claims

### Claim 1

A cell growth substrate composition, comprising:
a particulate material comprising a population of cell growth substrate particles each being a sheet having a sheet thickness of about 20 to about 2000 microns, wherein at least 25% of the substrate particles, when considered in the plane of the sheet, each have a first, maximum cross sectional dimension axis length which is no more than about two times the length of a second cross sectional axis taken on a line perpendicular to and centered upon the maximum cross sectional dimension axis, and wherein said cell growth substrate particles each comprise a membranous soft tissue with a sheet structure as isolated from a soft tissue source.

### Claim 2 (depends on 1)

The substrate composition of claim 1, wherein said cell growth substrate particles are characterized by having been cut from a larger sheet of cell growth substrate material, and wherein said cell growth substrate material is a membranous extracellular matrix tissue with a sheet structure.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the maximum cross sectional axis length is in the range of about 20 microns to about 2000 microns.

### Claim 4 (depends on 1)

The composition of claim 1, also comprising cells attached to said particles.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the cells cover substantially the entire outer surface of said particles.

### Claim 6 (depends on 5)

The composition of claim 5, wherein the cells form a substantially confluent monolayer covering the entire outer surface of said particles.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the cells comprise endothelial cells, endothelial progenitor cells, or a mixture thereof.

### Claim 8 (depends on 7)

The composition of claim 7, wherein the cells are clonal.

### Claim 9 (depends on 7)

The composition of claim 7, wherein the cells consist of endothelial cells, endothelial progenitor cells, or a mixture thereof.

### Claim 10 (depends on 1)

The composition of claim 1, wherein said cell growth substrate particles each have a generally circular, ovoid, or polygonal shape.

### Claim 11 (depends on 1)

The composition of claim 1, wherein the maximum cross sectional dimension axis length is greater than the sheet thickness.

### Claim 12 (depends on 1)

The composition of claim 1, wherein said soft tissue source is selected from the group comprising: submucosa, renal capsule membrane, dermal collagen, dura mater, pericardium, fascia lata, serosa, peritoneum, or basement membrane.

### Claim 13 (depends on 1)

A method for treating a patient, comprising:
introducing a particulate material of claim 1.

### Claim 14

An extracellular matrix composition, comprising:
a flowable particulate extracellular matrix material comprising membranous extracellular matrix particles each being a sheet, wherein said extracellular matrix particles are characterized by having been cut from a larger membranous soft tissue extracellular matrix sheet material to each have a generally circular, ovoid or polygonal shape and to each have a maximum cross sectional dimension axis length, considered in the plane of the sheet particles, in the range of about 100 to about 1500 microns, and wherein said extracellular matrix particles each have a thickness of about 20 to about 500 microns.

### Claim 15 (depends on 14)

The composition of claim 14, wherein for at least 25% of said extracellular matrix particles, the maximum cross sectional dimension axis length for each is no more than about two times the length of a second cross sectional axis taken on a line perpendicular to and centered upon the maximum cross sectional dimension axis.

### Claim 16 (depends on 15)

The composition of claim 15, wherein said extracellular matrix particles retain native growth factors from a source tissue for the larger extracellular matrix sheet material.

### Claim 17 (depends on 14)

The composition of claim 14, wherein said extracellular matrix particles retain native growth factors from a source tissue for the larger extracellular matrix sheet material.

### Claim 18 (depends on 14)

The composition of claim 14, also comprising cells attached to said particles.

### Claim 19 (depends on 18)

The composition of claim 18, wherein the cells cover substantially the entire outer surface of said particles.

### Claim 20 (depends on 19)

The composition of claim 19, wherein the cells form a substantially confluent monolayer covering the entire outer surface of said particles.

### Claim 21 (depends on 18)

The composition of claim 18, wherein the cells comprise endothelial cells, endothelial progenitor cells, or a mixture thereof.

### Claim 22 (depends on 21)

The composition of claim 21, wherein the cells are clonal.

### Claim 23 (depends on 21)

The composition of claim 21, wherein the cells consist of endothelial cells, endothelial progenitor cells, or a mixture thereof.

### Claim 24 (depends on 14)

The composition of claim 14, wherein said extracellular matrix particles each have a generally circular or ovoid shape.

### Claim 25 (depends on 14)

The composition of claim 14, wherein the maximum cross sectional dimension axis length is greater than the sheet thickness.

### Claim 26 (depends on 14)

The composition of claim 14, wherein said membranous soft tissue extracellular matrix sheet material is selected from the group comprising: submucosa, renal capsule membrane, dermal collagen, dura mater, pericardium, fascia lata, serosa, peritoneum, or basement membrane.