# US 10,864,234 B2 · Stem cell-based technologies for avian skeletal tissue engineering and regeneration

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- Number: US 10,864,234 B2
- Document ID: US10864234B2
- Status: Granted
- Kind: B2
- Application number: 15/525,570
- Filed: 2015-11-04
- Published: 2017-11-23
- Granted: 2020-12-15
- Earliest claimed: 2014-11-10
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Inventors: Rocky S. Tuan
- Web page: https://patentgrep.com/patent/US10864234B2

## CPC

- A61K 35/57: Birds; Materials from birds, e.g. eggs, feathers, egg white, egg yolk or endothelium corneum gigeriae galli
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61L 27/16: obtained by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/222: {Gelatin}
- A61L 27/3834: {Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells}
- A61L 27/3847: {Bones}
- A61L 27/3852: {Cartilage, e.g. meniscus}
- A61L 27/52: Hydrogels or hydrocolloids
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/10: for osteoporosis
- A61L 2300/64: Animal cells
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- A61L 2430/06: for cartilage reconstruction, e.g. meniscus
- 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)
- 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

## Abstract

Methods are disclosed for forming bone and/or cartilage in an avian subject. The methods include administering to the avian subject a therapeutically effective amount of a composition comprising avian mesenchymal stem cells and a hydrogel that supports the differentiation of the avian mesenchymal stem cells into cells of an osteogenic and/or condrogenic lineage. In some embodiments, methods are disclosed for repairing a bone defect and preventing infection, such as that associated bone fracture, in an avian subject. The methods include administering locally to the bone defect a composition comprising a therapeutically effective amount of avian mesenchymal stem cells and a hydrogel, such as a methacrylated gelatin hydrogel.

## Claims

### Claim 1

A method for forming bone and/or cartilage in an avian subject with a bone defect, comprising:
administering locally to the bone defect in the avian subject a therapeutically effective amount of a composition comprising avian mesenchymal stem cells and a hydrogel that supports the differentiation of the avian mesenchymal stem cells into cells of an osteogenic and/or chondrogenic lineage, wherein the hydrogel is a methacrylated gelatin hydrogel or methacrylated hyaluronan hydrogel, or a mixture thereof; and
photocrosslinking the hydrogel with visible light,
thereby forming bone and/or cartilage and treating the bone defect in the avian subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the hydrogel is biodegradable.

### Claim 3 (depends on 1)

The method of claim 1, wherein the hydrogel comprises methacrylated gelatin.

### Claim 4 (depends on 1)

The method of claim 1, further comprising administering to the avian subject at least one agent that induces or accelerates the differentiation of the mesenchymal stem cells into the osteogenic lineage.

### Claim 5 (depends on 1)

The method of claim 1, wherein the avian subject has a fracture, and avian mesenchymal stem cells and the hydrogel are delivered to the fracture.

### Claim 6 (depends on 5)

The method of claim 5, wherein the fracture is a result of trauma.

### Claim 7 (depends on 5)

The method of claim 5, wherein the fracture is result of an underlying physiological condition.

### Claim 8 (depends on 5)

The method of claim 5, wherein the underlying physiological condition is osteogenesis imperfecta or a metabolic bone disease.

### Claim 9 (depends on 1)

The method of claim 1, wherein the avian subject is a bird of the order Anseriformes, Apodiformes, Caprimulgiformes, Charadriiformes, Ciconiformes, Columbiformes, Coraciiformes, Falconiformes, Galliformes, Gaviidae, Passeriformes, Pelicaniformes, Phoenicopteriformes, Piciformes, Podicipediformes, Psittqciformes, or Strigidae.

### Claim 10 (depends on 1)

The method of claim 1, wherein the avian subject is an exo bird, a chicken, a pigeon, or a bird of prey.

### Claim 11 (depends on 1)

The method of claim 1, wherein the avian subject is a member of the family of Accipitridae, Pandionidae, Sagittariidae, Falconidae, Cathartidae, Strigidae or Tyonidae.

### Claim 12 (depends on 1)

The method of claim 1, wherein the avian subject is an owl, falcon or hawk.

### Claim 13 (depends on 1)

The method of claim 1, wherein the avian subject is a chicken.

### Claim 14 (depends on 1)

The method of claim 1, wherein the avian subject is a falcon.

### Claim 15

A method of repairing an infected hone defect in an avian subject, comprising:
administering locally to the bone defect a therapeutically effective amount of a composition comprising avian mesenchymal stern cells and a hydrogel, wherein the hydrogel is a methacrylated gelatin hydrogel or methacrylated hyaluronan hydrogel, or a mixture thereof; and
photocrosslinking the hydrogel with visible light,
thereby repairing the bone defect and treating the infection in the avian subject, wherein the infection is a Staphylococcus infection, an Escherichia coli infection, or an Enterococcus species infection.

### Claim 16 (depends on 15)

The method of claim 15, wherein the hydrogel is the methacrylated gelatin hydrogel.

### Claim 17 (depends on 15)

The method of claim 15, wherein the hydrogel is the methacrylated hyaluronan hydrogel.

### Claim 18 (depends on 15)

The method of claim 15, further comprising administering to the avian subject at least one agent that induces or accelerates the differentiation of the mesenchymal stem cells into the osteogenic lineage.

### Claim 19 (depends on 15)

The method of claim 15, wherein the avian subject is a bird of the order Anseriformes, Apodiformes, Caprimulgiformes, Charadriiformes, Ciconiformes, Columbiformes, Coraciiformes, Falconiformes, Galliformes, Gaviidae, Passeriformes, Pelicaniformes, Phoenicopteriformes, Piciformes, Podicipediformes, Psittqciformes, or Strigidae.

### Claim 20 (depends on 15)

The method of claim 15, wherein the avian subject is an exotic bird, a chicken, a pigeon, or a bird of prey.

### Claim 21 (depends on 15)

The method of claim 15, wherein the avian subject is a member of the family of Accipitridae, Pandionidae, Sagittariidae, Falconidae, Cathartidae, Strigidae or Tyonidae.
