# US 2019/0167843 A1 · Nerve guidance conduits, methods of production and uses thereof

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- Number: US 2019/0167843 A1
- Document ID: US20190167843A1
- Status: Published application
- Kind: A1
- Application number: 16/322,253
- Filed: 2017-08-01
- Published: 2019-06-06
- Earliest claimed: 2016-08-01
- Assignees: Association for the Advancement of Tissue Engineering and Cell Based Technologies & Therapie
- Applicants: Association for the Advancement of Tissue Engineering and Cell Based Technologies & Therapie
- Inventors: Cristiana RODRIGUES DE CARVALHO; João Pedro BEBIANO E COSTA; Viviana PINTO RIBEIRO; Joana Catarina DA SILVA CORREIA DE OLIVEIRA; Joaquim Miguel ANTUNES DE OLIVEIRA; Rui Luís GONÇALVES DOS REIS
- Web page: https://patentgrep.com/patent/US20190167843A1

## CPC

- A61L 27/227: {Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24}
- A61L 27/52: Hydrogels or hydrocolloids
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- A61L 27/225: {Fibrin; Fibrinogen}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 2430/32: for nerve reconstruction
- 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)

## Abstract

The present disclosure relates to a silk fibroin tubular conduit, a new methodology for obtaining said silk fibroin tubular conduit, and respective uses. The tubular conduit of the present disclosure can be used in treatment of diseases that involve the repair and/or regeneration of tissues, nerves or bone. In particular, the tubular conduit can be used for peripheral nerve regeneration.

## Claims

### Claim 1

A tubular conduit comprising an enzymatically cross-linked silk fibroin hydrogel, wherein said tubular conduit is predominantly β-sheet conformation and comprises a porosity up to 70% and a pore size up to 30 μm.

### Claim 2 (depends on 1)

The tubular conduit of claim 1, wherein the pore size up to 10 μm.

### Claim 3 (depends on 2)

The tubular conduit of claim 2, wherein the pore size is between 1-7 μm.

### Claim 4 (depends on 1)

The tubular conduit of claim 1, wherein the tubular conduit has a wall with a thickness of 0.2 mm-2 mm.

### Claim 5 (depends on 1)

The tubular conduit of claim 1, further comprising a conductive agent selected from the group consisting of: gold, silver, polypirrole, and mixtures thereof.

### Claim 6 (depends on 1)

The tubular conduit of claim 1, wherein the cross-linked silk fibroin hydrogel is enzymatically cross-linked with horseradish peroxidase and hydrogen peroxide.

### Claim 7 (depends on 1)

The tubular conduit of claim 1, wherein said hydrogel comprises between 5-25% (wt %) of silk fibroin.

### Claim 8 (depends on 1)

The tubular conduit of claim 1, wherein said hydrogel comprises between 12-18% (wt %) of silk fibroin.

### Claim 9 (depends on 1)

The tubular conduit of claim 1, wherein the porosity is 1-50%.

### Claim 10

(canceled)

### Claim 11 (depends on 1)

The tubular conduit of claim 1, wherein the tubular conduit has an internal diameter of 1 mm-10 mm.

### Claim 12 (depends on 1)

The tubular conduit of claim 1, wherein the tubular conduit has a length of 5 mm-100 mm.

### Claim 13 (depends on 1)

The tubular conduit of claim 1, wherein the tubular conduit further comprises hyaluronic acid, alginate, casein, polyethylene oxide, polyethylene glycol, collagen, fibronectin, keratin, polyaspartic acid, polylysine, chitosan, pectin, polylactic acid, polycaprolactone, polyglycolic acid, polyhydroxyalkanoate, polyanhydride, and mixtures thereof.

### Claim 14 (depends on 1)

The tubular conduit of claim 1, wherein the tubular conduit further comprises a biological active agent, a therapeutic agent, an additive, a pharmaceutically acceptable excipient, a pharmaceutically acceptable carrier, and mixtures thereof.

### Claim 15 (depends on 14)

The tubular conduit of claim 14, wherein the biologically active agent is selected from the following list: a peptide, a protein, a nucleic acid, an antibody, an aptamer, an anticoagulant agent, a growth factor, a cytokine, an antibiotic, an immunosuppressor, a steroid, non-steroidal anti-inflammatory drug, and mixtures thereof.

### Claim 16 (depends on 1)

The tubular conduit of claim 1, wherein the tubular conduit comprises dorsal root ganglia, Schwann cells and/or stem cells.

### Claim 17

A composition comprising a silk fibroin hydrogel enzymatically cross-linked with horseradish peroxidase and hydrogen peroxide, for use in medicine or in veterinary,
wherein said composition is administrated in a tubular conduit, and
wherein said tubular conduit comprises a β-sheet conformation obtainable from the enzymatically cross-linking of the silk fibroin hydrogel, porosity up to 70%, and a pore size up to 30 μm.

### Claim 18 (depends on 17)

The composition of claim 17, wherein the composition is a treatment for diseases that involve the repair and/or regeneration of tissues, nerves or bone.

### Claim 19

(canceled)

### Claim 20

(canceled)

### Claim 21

(canceled)

### Claim 22 (depends on 17)

The composition of claim 17, wherein the tubular conduit further comprises dorsal root ganglia and/or Schwann cells.

### Claim 23

(canceled)

### Claim 24 (depends on 1)

A method for producing the tubular conduit of claim 1, comprising:
preparing an aqueous silk fibroin solution with a concentration of 5-25% (wt %),
adding horseradish peroxidase and hydrogen peroxide to the aqueous silk fibroin solution to form an enzymatically cross-linked silk fibroin hydrogel;
injecting said silk fibroin hydrogel into a mould with desired dimensions, wherein said mould comprises an outer wall and an inter wall;
incubating the mould at 37° C. for 0.5-5 hours, for the complete formation of the hydrogel;
placing the silk fibroin hydrogel in liquid nitrogen for at least 30 seconds, until temporary development of β-sheet;
removing the outer wall of the mould; and
inducing a β-sheet conformation by placing in the silk fibroin hydrogel in an ethanol solution for at least 30 minutes or by freezing the silk fibroin hydrogel.

### Claim 25 (depends on 24)

The method of claim 24, further comprising drying the silk fibroin hydrogel by freeze drying for obtaining a pore size of 0.5 μm-2 μm.