# US 11,305,038 B2 · Vascular cast-based scaffolds and methods of making the same

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- Number: US 11,305,038 B2
- Document ID: US11305038B2
- Status: Granted
- Kind: B2
- Application number: 15/747,352
- Filed: 2016-07-21
- Published: 2018-08-02
- Granted: 2022-04-19
- Earliest claimed: 2015-07-24
- Assignees: Wake Forest University Health Sciences
- Applicants: Wake Forest University Health Sciences
- Inventors: James Yoo; In Kap Ko; Jennifer Huling; Anthony Atala
- Web page: https://patentgrep.com/patent/US11305038B2

## CPC

- A61L 27/56: Porous materials, {e.g. foams or sponges}
- A61K 35/44: Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
- A61L 27/20: Polysaccharides
- A61L 27/24: Collagen
- A61L 27/3804: {characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells}
- A61L 27/3808: {Endothelial cells}
- A61L 27/3821: {Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells}
- A61L 27/3826: {Muscle cells, e.g. smooth muscle cells}
- A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61L 27/507: {for artificial blood vessels (apparatus for applying cells on a blood vessel prosthesis A61F2/062)}
- A61L 27/52: Hydrogels or hydrocolloids
- A61K 35/33: Fibroblasts
- A61K 35/34: Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44)
- A61K 35/39: Pancreas; Islets of Langerhans (Langerhans cells of epidermis A61K35/36)
- A61K 35/407: Liver; Hepatocytes
- A61L 2430/20: for reconstruction of the heart, e.g. heart valves
- A61L 2430/22: for reconstruction of hollow organs, e.g. bladder, esophagus, urether, uterus
- A61L 2430/28: for liver reconstruction
- A61L 2430/30: for muscle reconstruction
- C12M 25/14: {Scaffolds; Matrices (in general C12N5/0068)}
- 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)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- 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}

## Abstract

The present application relates to biomimetic three-dimensional (3D) scaffolds, constructs and methods of making the same. The three-dimensional scaffold can include a sacrificial internal cast and a durable external scaffold material, wherein the durable external scaffold material comprises a biocompatible material which completely surrounds the sacrificial internal cast and wherein the sacrificial internal cast be removed to yield a branching 3D network of hollow, vessel-like tubes that substantially mimics a native tissue or organ.

## Claims

### Claim 1

A method of creating a three-dimensional, hollow vascular scaffold comprising:
obtaining a sample comprising native tissue with an internal vasculature;
perfusing a sacrificial internal casting composition into the native tissue vasculature;
solidifying the sacrificial internal casting composition within the native tissue vasculature;
digesting the native tissue, thereby creating a sacrificial solid cast of the native tissue vasculature;
coating the sacrificial solid cast of the native tissue vasculature with a durable biocompatible outer scaffold material that surrounds the sacrificial solid cast of the native tissue vasculature;
removing the sacrificial solid cast, thereby forming a three-dimensional, hollow vascular scaffold with a branching 3D network of hollow vessel-like tubes that mimics the original vasculature of the native tissue; and
seeding the scaffold with a population of endothelial or endothelial progenitor cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the sacrificial internal casting composition comprises polycaprolactone.

### Claim 3 (depends on 2)

The method of claim 2, wherein the sacrificial internal casting composition is a solution comprising about 5% to about 30% polycaprolactone.

### Claim 4 (depends on 1)

The method of claim 1, wherein the sacrificial internal casting composition comprises gallium.

### Claim 5 (depends on 1)

The method of claim 1, wherein the durable biocompatible outer scaffold material comprises collagen.

### Claim 6 (depends on 1)

The method of claim 1, wherein the step of digesting the native tissue further comprises digesting the native tissue surrounding the sacrificial solid cast.

### Claim 7 (depends on 1)

The method of claim 1, wherein the step of digesting the native tissue further comprises enzymatic digestion of the native tissue surrounding the sacrificial solid cast.

### Claim 8 (depends on 1)

The method of claim 1 wherein the step of removing the sacrificial solid cast further comprises dissolving the sacrificial solid cast with a solvent.

### Claim 9 (depends on 8)

The method of claim 8, wherein the solvent is an organic solvent.

### Claim 10 (depends on 1)

The method of claim 1 wherein the step of removing the solid cast further comprises raising a temperature of sacrificial solid cast to liquefy the sacrificial solid cast.

### Claim 11 (depends on 1)

The method of claim 1, further comprising seeding an internal surface, an external surface, or a combination thereof of the three-dimensional, hollow vascular scaffold with said population of endothelial or endothelial progenitor cells.

### Claim 12 (depends on 11)

The method of claim 11, wherein the population of cells comprises endothelial cells.

### Claim 13 (depends on 11)

The method of claim 11, wherein the population of cells comprises endothelial progenitor cells.

### Claim 14 (depends on 1)

The method of claim 1, further comprising embedding the three-dimensional vascular scaffold in a hydrogel.

### Claim 15 (depends on 14)

The method of claim 14, wherein the hydrogel comprises a population of cells.

### Claim 16 (depends on 14)

The method of claim 14, wherein the population of cells comprises skeletal muscle cells, smooth muscle cells, fibroblasts, renal cells, hepatocytes, pancreatic islet cells or beta-cells, smooth muscle cells or combinations thereof.

### Claim 17

A three-dimensional, hollow scaffold having a branching 3D network of hollow vessel-like tubes that mimics the original vasculature of native tissue comprising:
a durable external scaffold layer on a portion of vascular corrosion cast;
wherein the durable external scaffold layer comprises a biocompatible material that promotes endothelial cell or endothelial progenitor cell seeding and is formed by perfusing a sacrificial internal casting composition into a tissue vasculature; solidifying the sacrificial internal casting composition within the native vasculature; digesting the native vasculature, thereby creating a solid cast of the native vasculature; coating the solid cast with a biocompatible outer casting material; and removing the sacrificial internal casting composition thus forming a three-dimensional, hollow scaffold having a branching 3D network of hollow vessel-like tubes that mimics the original vasculature of native tissue.

### Claim 18 (depends on 17)

The scaffold of claim 17, wherein the biocompatible material comprises collagen or chitosan.

### Claim 19 (depends on 17)

The scaffold of claim 17, wherein the biocompatible material forms a biomimetic scaffold of at least one of a renal vasculature, a gastrointestinal vasculature, a nervous system vasculature, a pulmonary vasculature, a cardiac vasculature, a hepatic vasculature, a splenic vasculature, a pancreatic vasculature, or a musculoskeletal vasculature.

### Claim 20 (depends on 19)

The scaffold of claim 19, wherein the population of cells comprises endothelial cells or endothelial progenitor cells.

### Claim 21 (depends on 17)

The scaffold of claim 17, wherein the scaffold is seeded with a population of cells onto an internal surface, an external surface, or a combination thereof of the scaffold.