# US 2016/0256607 A1 · Compressed bone composition and methods of use thereof

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- Number: US 2016/0256607 A1
- Document ID: US20160256607A1
- Status: Published application
- Kind: A1
- Application number: 15/028,639
- Filed: 2014-10-09
- Published: 2016-09-08
- Earliest claimed: 2013-10-09
- Assignees: LifeNet Health
- Applicants: Lifenet Health
- Inventors: Michael Francis; Rudy Rodriguez; Nathan Kemper
- Web page: https://patentgrep.com/patent/US20160256607A1

## CPC

- A61L 27/3608: {Bone, e.g. demineralised bone matrix [DBM], bone powder}
- A61F 2/28: Bones
- A61L 27/365: {Bones}
- 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 27/502: {Plasticizers}
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- B28B 1/007: {by freezing the material}
- B28B 17/02: Conditioning the material prior to shaping {(for mixtures containing clay or cement B28C)}
- A61F 2002/2817: {Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]}
- A61F 2002/2828: {Femoral head}
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- B33Y 80/00: Products made by additive manufacturing
- 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)
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)
- B28B: SHAPING CLAY OR OTHER CERAMIC COMPOSITIONS; SHAPING SLAG; SHAPING MIXTURES CONTAINING CEMENTITIOUS MATERIAL, e.g. PLASTER (foundry moulding B22C; working stone or stone-like material B28D; shaping of substances in a plastic state, in general B29C; making layered products not composed wholly of these substances B32B)
- B33Y: ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING

## Abstract

The present disclosure relates to compressed bone compositions, bone implants, and variants thereof. The present disclosure also relates to methods of preparing compressed bone compositions, bone implants, and variants thereof. The present disclosure also relates to methods of using the bone compositions, bone implants and variants thereof.

## Claims

### Claim 1

A method for preparing a compressed bone composition, comprising:
loading bone particles into a mold with a predetermined shape,
applying pressure between about 0.1 and 30 MPa to the bone particles, and
freeze drying the compressed bone particles to create the compressed bone composition.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the pressure is from about 0.1 MPa to about 6 MPa.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the pressure is between 100 psi and 1000 psi.

### Claim 4 (depends on 1)

The method according to claim 1, wherein said predetermined shape comprises grooves.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the compressed bone composition retains its integrity in liquid for at least 5-30 minutes.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the pressure is applied at room temperature.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the compressed bone composition does not comprise a binder or a chemical cross-linker.

### Claim 8 (depends on 1)

The method according to claim 1, wherein said bone particles comprise bone fiber, bone powder, or a mixture of bone fiber and bone powder.

### Claim 9 (depends on 1)

The method according to claim 1, wherein said bone particles are from cortical bone, cancellous bone, cortical cancellous bone, or a mixture of cortical and cancellous bone.

### Claim 10 (depends on 1)

The method according to claim 1, further comprising demineralizing the bone particles prior to applying the pressure.

### Claim 11 (depends on 1)

The method according to claim 1, further comprising cleaning the bone particles prior to applying the pressure.

### Claim 12 (depends on 11)

The method according to claim 11, wherein said cleaning comprising incubating the bone particles with an antibiotic, a detergent, an alcohol, and/or a H2O2.

### Claim 13 (depends on 11)

The method according to claim 11, wherein said cleaning comprising using the Allowash® process.

### Claim 14 (depends on 1)

The method according to claim 1, further comprising sterilizing the compressed bone composition.

### Claim 15 (depends on 14)

The method according to claim 14, wherein the bone particles are sterilized by gamma or e-beam Irradiation, ethylene oxide, or critical CO2.

### Claim 16 (depends on 1)

The method according to claim 1, further comprising treating the compressed bone composition with a plasticizer composition.

### Claim 17 (depends on 16)

The method according to claim 16, wherein said plasticizer composition comprises one or more plasticizers selected from the group consisting of glycerol, adonitol, sorbitol, ribitol, galactitol, D-galactose, 1,3-dihydroxypropanol, ethylene glycol, triethylene glycol, propylene glycol, glucose, sucrose, mannitol, xylitol, meso-erythritol, adipic acid, proline, hydroxyproline, polyol, and a fatty acid.

### Claim 18 (depends on 1)

The method according to claim 1, wherein said bone particles are obtained from a human, a cow, a pig, a dog, a horse, a goat, or a sheep.

### Claim 19 (depends on 1)

A bone implant prepared by the method according to claim 1, wherein the structure comprises grooves.

### Claim 20 (depends on 19)

The bone implant according to claim 19, wherein said bone particle is from a human, a cow, a pig, a dog, a horse, a goat, or a sheep.

### Claim 21 (depends on 19)

The bone implant according to claim 19, wherein said bone particles comprise bone fiber, bone powder, or a mixture of bone fiber and bone powder.

### Claim 22 (depends on 19)

The bone implant according to claim 19, wherein said bone particles are demineralized.

### Claim 23 (depends on 19)

The bone Implant according to claim 19, wherein said bone particles have an average residual calcium content of 0.01-8 wt %.

### Claim 24 (depends on 19)

The bone implant according to claim 19, wherein said bone particles have an average residual calcium content of 0.01-4 wt %.

### Claim 25 (depends on 19)

The bone implant according to claim 19, wherein said bone particles are from cortical bone, cancellous bone, cortical cancellous bone, or a mixture of cortical and cancellous bone.

### Claim 26 (depends on 19)

The bone implant according to claim 19, wherein said bone implant further comprises at least one cell and/or at least one bioactive factor.

### Claim 27 (depends on 19)

The bone implant according to claim 19, wherein said bone implant has a higher density at the groove areas compared to rest of the structure.

### Claim 28 (depends on 19)

The bone implant according to claim 19, wherein the density of the bone implant is between about 0.24 and 0.35 g/cm3.

### Claim 29 (depends on 19)

The bone implant according to claim 19, wherein said bone particles have a median diameter of about 10-1,000 microns, a median length of about 0.5-100 mm, and a median thickness of about 10-1000 microns.

### Claim 30 (depends on 19)

The bone implant according to claim 19, wherein said bone implant does not comprise a binder or a chemical cross-linker.

### Claim 31

A bone composition comprising bone fibers, wherein the bone fibers comprise microfibers having an average width (W) of less than about 5 μm and an average length (L):W ratio of greater than about 2.

### Claim 32 (depends on 31)

The bone composition of claim 31, wherein the average L:W ratio is greater than about 5.

### Claim 33 (depends on 31)

The bone composition of claim 31, wherein the average L:W ratio is greater than about 7.

### Claim 34 (depends on 31)

The bone composition of claim 31, wherein the average L:W ratio is in a range from 2 to 30.

### Claim 35 (depends on 31)

The bone composition of claim 31, wherein the average L:W ratio is in a range from 5 to 8.

### Claim 36 (depends on 31)

The bone composition of claim 31, wherein the W of the microfibers is less than about 2 μm.

### Claim 37 (depends on 31)

The bone composition of claim 31, wherein the W of the microfibers is less than about 1 μm.

### Claim 38 (depends on 31)

The bone composition of claim 31, wherein the L of the microfibers is less than about 12 μm.

### Claim 39 (depends on 31)

The bone composition of claim 31, wherein the L of the microfibers is less than about 7 μm.

### Claim 40 (depends on 31)

The bone composition of claim 31, wherein the bone compositions are prepared by applying pressure to bone fibers.

### Claim 41 (depends on 31)

The bone composition of claim 31, wherein the bone composition is wet and the mode of the pore sizes of the wet bone composition is in a range from 25 to 250 μm.

### Claim 42 (depends on 41)

The bone composition of claim 41, wherein the mode of pore sizes of the wet bone composition at equilibrium does not have a bimodal distribution.

### Claim 43 (depends on 31)

The bone composition of claim 31, wherein when the bone composition is wet, the mean of the pore sizes of the wet bone composition is in a range from 20 to 100 μm.

### Claim 44 (depends on 43)

The bone composition of claim 43, wherein the mean of pore sizes of the wet bone composition at equilibrium is less than 30 μm or more than 65 μm.

### Claim 45

A method of making a bone implant for an individual, the method comprising:
loading bone composition into a mold that is based upon three dimensional (3D) measurements taken from a bone structure of the individual for the implant, wherein the bone composition comprises microfibers having an average length (L):average width (W) ratio greater than about 2;
applying pressure of between about 0.1 and 30 MPa to the bone composition to fit the mold; and
freeze drying the compressed bone composition to make the bone implant.

### Claim 46 (depends on 45)

The method of claim 45, wherein the mold is constructed with 3-D printing.

### Claim 47 (depends on 45)

The method of claim 45, wherein the individual is a human, a dog, a pig, a cow, a cat or a horse.

### Claim 48 (depends on 45)

The method of claim 45, wherein the individual is a human.

### Claim 49 (depends on 45)

The method of claim 45, wherein the bone structure is a segmental defect without load bearing.

### Claim 50 (depends on 45)

The method of claim 45, wherein the bone structure is selected from a group consisting of a femoral head, a femur trochanter, a skull flap, and mandible.

### Claim 51 (depends on 45)

The method of claim 45, wherein the mold comprises a groove.

### Claim 52

A method of promoting osteoinductivity, osteoconductivity, chondroinductivity, chondroconductivity, or ligament/tendon differentiation or growth of cells, comprising contacting cells with a bone composition comprising bone fibers, wherein the bone fibers comprise microfibers having an average width (W) of less than about 5 μm and an average length (L):W ratio of greater than about 2.

### Claim 53 (depends on 52)

The method of claim 52, wherein the cells are progenitor cells or adult stem cells.

### Claim 54 (depends on 53)

The method of claim 53, wherein the progenitor cells or the adult stem cells are derived from placenta, bone marrow, adipose tissue, blood vessel, amniotic fluid, synovial fluid, synovial membrane, pericardium, periosteum, dura, peripheral blood, umbilical blood, menstrual blood, baby teeth, nucleus pulposus, brain, skin, hair follicle, Intestinal crypt, neural tissue, or muscle.

### Claim 55 (depends on 45)

The method of claim 45, further comprising applying the bone Implant to a prosthesis.

### Claim 56 (depends on 55)

The method of claim 55, wherein the prosthesis comprises a metal or a synthetic material.