# US 10,478,524 B2 · Tissue-engineered silk organs

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- Number: US 10,478,524 B2
- Document ID: US10478524B2
- Status: Granted
- Kind: B2
- Application number: 15/600,351
- Filed: 2017-05-19
- Published: 2018-02-08
- Granted: 2019-11-19
- Earliest claimed: 2007-02-27
- Assignees: Trustees of Tufts College
- Applicants: Trustees of Tufts College
- Inventors: David L. Kaplan; Fiorenzo G. Omenetto; Jeffrey K. Marchant; Noorjahan Panjwani; Brian Lawrence
- Web page: https://patentgrep.com/patent/US10478524B2

## 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 27/225: {Fibrin; Fibrinogen}
- A61L 27/227: {Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24}
- A61L 27/3804: {characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells}
- A61L 27/3839: {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 27/3891: {as distinct cell layers}
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- C12N 5/0068: {General culture methods using substrates (for specific animal cell type C12N5/06)}
- C12N 5/0621: {Eye cells, e.g. cornea, iris pigmented cells (photoreceptors C12N5/062)}
- G01N 33/5044: {involving specific cell types}
- A61L 2300/412: Tissue-regenerating or healing or proliferative agents
- C12N 2533/50: Proteins
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

This invention relates to a lamellae tissue layer, comprising a grooved silk fibroin substrate comprising tissue-specific cells. The silk fibroin substrates provides an excellent means of controlling and culturing cell and extracellular matrix development. A multitude of lamellae tissue layers can be used to create a tissue-engineered organ, such as a tissue-engineered cornea. The tissue-engineered organ is non-immunogenic and biocompatible.

## Claims

### Claim 1

A grooved substrate comprising silk fibroin,
wherein thickness of the substrate ranges from 10 nm to 1 mm,
wherein groove width is at least 125 nm, and
wherein the substrate comprises micropores,
wherein spacing between the micropores is 50 μm to 100 μm and,
wherein an average diameter of the micropores ranges from 100 nm to 10 μm.

### Claim 2 (depends on 1)

The grooved substrate of claim 1, wherein groove thickness depth is at least 100 nm.

### Claim 3 (depends on 1)

The grooved substrate of claim 1, wherein the silk is selected from the group consisting of silkworm silk, spider silk, transgenic silk and genetically engineered silk.

### Claim 4 (depends on 1)

The grooved substrate of claim 1, wherein the substrate comprises patterned diffractive optical surfaces.

### Claim 5 (depends on 1)

The grooved substrate of claim 1, wherein the substrate comprises beta-sheet crystallinity, and
wherein the beta-sheet crystallinity is induced by water annealing.

### Claim 6 (depends on 1)

The grooved substrate of claim 1, wherein the micropores are created through the use of poly(ethylene oxide) phase separation chemistry, laser ablation techniques, or a combination thereof.

### Claim 7 (depends on 1)

The grooved substrate of claim 1, wherein the substrate is non-immunogenic, and biocompatible.

### Claim 8 (depends on 1)

The grooved substrate of claim 1, further comprising at least one non-patterned silk film or circular patterned silk film.