# US 2018/0021382 A1 · Modification of reactivity of bone constructs

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2018/0021382 A1
- Document ID: US20180021382A1
- Status: Published application
- Kind: A1
- Application number: 15/703,166
- Filed: 2017-09-13
- Published: 2018-01-25
- Earliest claimed: 2012-01-30
- Assignees: Warsaw Orthopedic, Inc.
- Applicants: Warsaw Orthopedic, Inc.
- Inventors: Guobao Wei; Susan J. Drapeau
- Web page: https://patentgrep.com/patent/US20180021382A1

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 35/32: Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
- A61L 27/3608: {Bone, e.g. demineralised bone matrix [DBM], bone powder}
- A61L 27/3683: {subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment}
- A61L 27/3821: {Bone-forming cells, e.g. osteoblasts, osteocytes, osteoprogenitor cells}
- 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 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61P 19/00: Drugs for skeletal disorders
- A61L 2300/414: Growth factors
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- 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

A method of enhancing the binding of growth factors and cell cultures to a demineralized allograft bone material which includes applying ex vivo an effective quantity of an ionic force change agent to at least a portion of the surface of a demineralized allograft bone material to produce a binding-sensitized demineralized allograft bone material and implanting the binding-sensitized demineralized allograft bone material into a host bone. The ionic force change agent may include at least one of enzymes, pressure, chemicals, heat, sheer force, oxygen plasma, supercritical nitrogen, supercritical carbon, supercritical water or a combination thereof. A molecule, a cell culture, or a combination thereof is administered to the binding-sensitized demineralized allograft bone material.

## Claims

### Claim at position 1

1-10. (canceled)

### Claim 11

A method of enhancing the binding of growth factors and cell cultures to a demineralized allograft bone material, the method comprising applying an effective quantity of an ionic force change agent to at least a portion of the surface of the demineralized allograft bone material to produce a binding-sensitized demineralized allograft bone material; implanting the binding-sensitized demineralized allograft bone material into a host bone; and administering to the binding-sensitized demineralized allograft bone material a growth factor, a cell culture, or a combination thereof.

### Claim 12 (depends on 11)

A method of claim 11, wherein the growth factor or cell culture or a combination thereof is administered to the binding-sensitized demineralized allograft bone material prior to the implantation of the binding-sensitized demineralized allograft bone material into the host bone.

### Claim 13 (depends on 11)

A method of claim 11, wherein the growth factor, the cell culture, or the combination thereof is capable of binding to the binding-sensitized demineralized allograft bone material.

### Claim 14 (depends on 11)

A method of claim 11, wherein the ionic force change agent comprises at least one of enzymes, pressure, heat, sheer force, oxygen plasma, supercritical nitrogen or supercritical carbon, supercritical water or a combination thereof.

### Claim 15 (depends on 11)

A method of claim 11, wherein the growth factor comprises at least one of BMP-2, rhBMP-2, BMP-4, rhBMP-4, BMP-6, rhBMP-6, BMP-7 (OP-1), rhBMP-7, GDF-5, LIM mineralization protein, platelet derived growth factor (PDGF), transforming growth factor-β (TGF-β), insulin-related growth factor-I (IGF-I), insulin-related growth factor-II (IGF-II), fibroblast growth factor (FGF), beta-2-microglobulin (BDGF II), rhGDF-5, or a combination thereof.

### Claim 16 (depends on 11)

A method of claim 11, wherein the cell culture comprises at least one of mesenchymal stems cells, periosteal cells, pluripotent stem cells, osteoprogenitor cells, osteoblasts, osteoclasts, a bone marrow-derived cell lines, or a combination thereof.

### Claim 17 (depends on 11)

A method of claim 11, wherein the growth factor comprises tartrate-resistant acid phosphatase.

### Claim at position 9

-20. (canceled)

### Claim 21 (depends on 11)

A method of claim 11, wherein the applying the effective quantity of the ionic force change agent to the demineralized allograft bone material comprises applying an enzyme comprising cathepsin L, cathepsin K, cathepsin B, plasminogen, plasminogen activators, elastase or stromelysin to the demineralized allograft bone material.

### Claim 22 (depends on 11)

A method of claim 11, wherein the applying the effective quantity of the ionic force change agent to the demineralized allograft bone material comprises applying an enzyme comprising cathepsin L to the demineralized allograft bone material.

### Claim 23 (depends on 11)

A method of claim 11, wherein the applying the effective quantity of the ionic force change agent to the demineralized allograft bone material comprises applying an enzyme comprising cathepsin K to the demineralized allograft bone material.

### Claim 24 (depends on 11)

A method of claim 11, wherein the applying the effective quantity of the ionic force change agent to the demineralized allograft bone material comprises applying an enzyme comprising cathepsin B to the demineralized allograft bone material.

### Claim 25 (depends on 11)

A method of claim 11, wherein the applying the effective quantity of the ionic force change agent to the demineralized allograft bone material comprises applying an enzyme comprising plasminogen to the demineralized allograft bone material.

### Claim 26 (depends on 11)

A method of claim 11, wherein the applying the effective quantity of the ionic force change agent to the demineralized allograft bone material comprises applying an enzyme comprising plasminogen activators to the demineralized allograft bone material.

### Claim 27 (depends on 11)

A method of claim 11, wherein the applying the effective quantity of the ionic force change agent to the demineralized allograft bone material comprises applying an enzyme comprising elastase to the demineralized allograft bone material.

### Claim 28 (depends on 11)

A method of claim 11, wherein the applying the effective quantity of the ionic force change agent to the demineralized allograft bone material comprises applying an enzyme comprising stromelysin to the demineralized allograft bone material.