# US 11,896,736 B2 · Biomaterial implants and methods of making the same

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- Number: US 11,896,736 B2
- Document ID: US11896736B2
- Status: Granted
- Kind: B2
- Application number: 16/926,905
- Filed: 2020-07-13
- Published: 2022-01-13
- Granted: 2024-02-13
- Earliest claimed: 2020-07-13
- Assignees: Globus Medical, Inc.
- Applicants: Globus Medical, Inc.
- Inventors: Joshua Cige; Archana Bhat; Joanna Marquez
- Web page: https://patentgrep.com/patent/US11896736B2

## CPC

- A61L 27/3608: {Bone, e.g. demineralised bone matrix [DBM], bone powder}
- A61F 2/28: Bones
- A61F 2/4644: {Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material (bone material A61F2/28; disintegrating or milling devices B02C)}
- A61L 27/3616: {Blood, e.g. platelet-rich plasma}
- A61L 27/365: {Bones}
- 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 27/3687: {characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents}
- A61L 27/3691: {characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation}
- A61L 27/3804: {characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells}
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- A61L 2430/40: Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
- 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)

## Abstract

Biomaterials, implants made therefrom, methods of making the biomaterial and implants, methods of promoting bone or wound healing in a mammal by administering the biomaterial or implant to the mammal, and kits that include such biomaterials, implants, or components thereof. The biomaterials may include demineralized cortical fibers, which help to promote bone repair.

## Claims

### Claim 1

A method of making an implantable biomaterial for aiding bone regeneration, the method comprising:
obtaining whole bone;
sectioning and debriding the whole bone into cortical rings;
machining the cortical rings into cortical fibers having lengths of 10-50 mm, widths of 0.5-2 mm, and thicknesses of 0.1-1 mm;
demineralizing the cortical fibers to form demineralized cortical fibers;
suspending and entangling the demineralized cortical fibers in an aqueous solution;
compressing the demineralized cortical fibers in solution in a mold to form a molded biomaterial composition of a given shape;
freezing the molded biomaterial composition; and
freeze-drying the molded biomaterial composition to form the implantable biomaterial;
wherein the cortical rings are cleaned with a 0.05-0.15% v/v sodium deoxycholate solution, a 2-6% hydrogen peroxide solution, and an isopropyl alcohol solution.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cortical rings are sectioned into lengths of 10-30 mm.

### Claim 3 (depends on 1)

The method of claim 1, wherein the cortical rings are cleaned with a 0.1% v/v sodium deoxycholate/sterile saline solution, a 3% hydrogen peroxide solution, a 70% isopropyl alcohol solution, and warm sterile water.

### Claim 4 (depends on 1)

The method of claim 1, wherein an outer two-thirds of the cortical ring wall thickness is machined into fibers and a remaining one-third is discarded.

### Claim 5 (depends on 1)

The method of claim 1, wherein the cortical fibers are demineralized using an acid treatment with a 0.6N hydrochloric acid treatment followed by a buffer rinse to obtain a neutral pH.

### Claim 6 (depends on 1)

The method of claim 1, wherein the cortical fibers are suspended in sterile water and entangled under agitation.

### Claim 7 (depends on 1)

The method of claim 1, wherein the cortical fibers are compressed in the mold and drain holes in the mold allow for drainage of excess water.

### Claim 8 (depends on 1)

The method of claim 1, wherein the mold is packed at a 1:1 To 2:1 ratio, in cubic centimeters, of demineralized cortical fiber to mold volume.

### Claim 9 (depends on 1)

The method of claim 1, wherein prior to use, further comprising reconstituting the dried implantable biomaterial with a cellular material.

### Claim 10 (depends on 9)

The method of claim 9, wherein the cellular material is red blood cells, white blood cells, platelets, blood plasma, and/or bone marrow cells.

### Claim 11 (depends on 1)

The method of claim 1, wherein the cleaning step is performed after sectioning, but prior to demineralizing.

### Claim 12

A method of promoting bone or wound healing in a mammal, the method comprising:
cleaning cortical fibers with a 0.05-0.15% v/v sodium deoxycholate solution, a 2-6% hydrogen peroxide solution, and an isopropyl alcohol solution;
demineralizing the cleaned cortical fibers to form demineralized cortical fibers;
entangling and compressing the demineralized cortical fibers having lengths of 10-50 mm, widths of 0.5-2 mm, and thicknesses of 0.1-1 mm into a bone graft, wherein any excess water is drained from the bone graft during compressing;
administering the bone graft into a target repair site to facilitate repair or regeneration of bone at the target repair site.

### Claim 13 (depends on 12)

The method of claim 12, wherein the target repair site is an injury or defect in the spine.

### Claim 14

A method of making an implantable biomaterial for aiding bone regeneration, the method comprising:
obtaining whole bone;
separating the whole bone into condyles and cortical shafts;
grinding the condyles into cortico-cancellous chips having a size less than 1.5 mm;
machining the cortical shafts into cortical fibers having a size of 15-30 mm;
demineralizing the cortical fibers;
combining the cortico-cancellous chips and demineralized cortical fibers with a carrier, wherein the carrier is a reverse phase hydrogel;
wherein prior to demineralizing, the cortical shafts are cleaned with a 0.05-0.15% v/v sodium deoxycholate solution, a 2-6% hydrogen peroxide solution, and an isopropyl alcohol solution.

### Claim 15 (depends on 14)

The method of claim 14, wherein the carrier is a 25-45% (w/v) solution with poloxamer, glycerol, carboxymethyl cellulose, or sodium hyaluronate.

### Claim 16 (depends on 15)

The method of claim 15, wherein the carrier is a 35% (w/v) solution with poloxamer.

### Claim 17 (depends on 14)

The method of claim 14, wherein the implantable biomaterial is a putty including 40-70% demineralized cortical fibers, 20-40% cancellous chips in a size range of 100-500 μm, and 10-40% carrier.

### Claim 18 (depends on 14)

The method of claim 14, wherein the cortico-cancellous chips have a bimodal distribution of 100-500 μm and 500-1500 μm.

### Claim 19 (depends on 18)

The method of claim 18, wherein the implantable biomaterial is a crunch including 40-70% demineralized cortical fibers, 10-30% cortico-cancellous chips in a size range of 100-500 μm, 10-30% cortico-cancellous chips in a size range of 500-1500 μm, and 10-40% carrier.

### Claim 20 (depends on 14)

The method of claim 14, wherein the condyles and cortical shafts undergo a liquid processing including an antibiotic/antimycotic solution for 10-15 minutes, 0.05-0.15% v/v sodium deoxycholate solution for 15-35 minutes, 2-6% (w/v) hydrogen peroxide solution for 15-35 minutes, and 70% isopropyl alcohol for 5-15 minutes with intermediate rinse steps using sterile water.