# US 9,427,497 B2 · Bone regeneration using biodegradable polymeric nanocomposite materials and applications of the same

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

- Number: US 9,427,497 B2
- Document ID: US9427497B2
- Status: Granted
- Kind: B2
- Application number: 14/506,438
- Filed: 2014-10-03
- Published: 2015-01-29
- Granted: 2016-08-30
- Earliest claimed: 2005-09-09
- Assignees: Board of Trustees of the University of Arkansas
- Applicants: Board of Trustees of the University of Arkansas
- Inventors: Alexandru S. Biris
- Web page: https://patentgrep.com/patent/US9427497B2

## CPC

- A61L 27/58: Materials at least partially resorbable by the body
- A61F 2/28: Bones
- A61F 2/2846: {Support means for bone substitute or for bone graft implants, e.g. membranes or plates for covering bone defects (nets or sleeves applied to surface of endoprostheses A61F2/30907; bone plates A61B17/80; bone regeneration in dental surgery A61C8/0006)}
- A61L 27/3608: {Bone, e.g. demineralised bone matrix [DBM], bone powder}
- A61L 27/365: {Bones}
- A61L 27/38: {containing added animal cells (organs or tissue containing native cells A61L27/36)}
- A61L 27/44: having a macromolecular matrix
- A61L 27/46: with phosphorus-containing inorganic fillers
- A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- A61F 2002/2835: {Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material}
- A61L 2300/412: Tissue-regenerating or healing or proliferative agents
- A61L 2300/414: Growth factors
- A61L 2300/64: Animal cells
- A61L 2400/12: Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
- A61L 2400/18: Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- Y10T 156/1062: Prior to assembly
- Y10T 156/1075: of plural laminae from single stock and assembling to each other or to additional lamina
- 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)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

A structure of, and a method of producing, a biocompatible structure for bone and tissue regeneration are disclosed. The method includes dissolving a polyurethane polymer in methanol, adding hydroxyapatite (HAP) nanoparticles to form a uniformly distributed mixture, applying the mixture to a polytetrafluoroethylene (PTFE) surface to form a polymer film, cutting the polymer film into strips, stacking the strips with layers of bone particles disposed therebetween, coating the stacked strips and layers by the mixture and allowing it to dry, adding bone particles to the coating, and plasma treating the structure to form the biocompatible structure. A weight percentage of the HAP nanoparticles to the polymer is about 5-50% such that a resorption rate of the biocompatible structure substantially matches a rate of tissue generation in the biocompatible structure.

## Claims

### Claim 1

A method of producing a biocompatible structure for bone and tissue regeneration, comprising:
dissolving a polymer in a solvent to form a first solution;
adding first tissue forming nanoparticles to the first solution to form a second solution wherein a weight percentage of the first tissue forming nanoparticles to the polymer is about 0.01-95%;
applying the second solution to a surface to form a polymer film on the surface, wherein the first tissue forming nanoparticles are dispersed in the polymer film;
dividing the polymer film into strips;
constructing a scaffold by stacking the strips to form polymer layers and adding bone or composite particles between the polymer layers;
applying the second solution to the scaffold to form a first coating layer surrounding the scaffold; and
adding second tissue forming particles to the first coating layer to form a second coating layer surrounding the first coating layer, so as to obtain the biocompatible structure.

### Claim 2 (depends on 1)

The method of claim 1, further comprising stirring the first solution to uniformly distribute the polymer in the first solution.

### Claim 3 (depends on 1)

The method of claim 1, further comprising sonicating the second solution to uniformly distribute the polymer and the first tissue forming nanoparticles in the second solution.

### Claim 4 (depends on 1)

The method of claim 1, further comprising drying the second solution on the surface to form the polymer film on the surface.

### Claim 5 (depends on 1)

The method of claim 1, wherein the scaffold is formed by stacking the strips and layers of the bone particles alternatively.

### Claim 6 (depends on 5)

The method of claim 5, further comprising plasma treating the scaffold surrounded with the first coating layer and the second coating layer.

### Claim 7 (depends on 1)

The method of claim 1, wherein the weight percentage of the first tissue forming nanoparticles to the polymer is about 20%.

### Claim 8 (depends on 1)

The method of claim 1,
wherein the polymer comprises a synthetic biodegradable polymer, a biodegradable polymer from a natural source, or a mixture thereof;
wherein the synthetic biodegradable polymer comprises polyurethane, polylactide (PLA), polyglycolide (PGA), poly(lactide-co-glycolide) (PLGA), poly(e-caprolactone), polydioxanone, polyanhydride, trimethylene carbonate, poly((β-hydroxybutyrate), poly(g-ethyl glutamate), poly(desaminotyrosyl-tyrosine-hexyl ester (DTH) iminocarbonate), poly(bisphenol A iminocarbonate), poly(ortho ester), polycyanoacrylate, polyphosphazene, or a mixture thereof.

### Claim 9 (depends on 1)

The method of claim 1, wherein the first tissue forming nanoparticles comprise nanoparticles of hydroxypatites, tricalcium phosphates, mixed calcium phosphates and calcium carbonate, bone particles of zenograft, bone particles of allografts, bone particles of autografts, bone particles of alloplastic grafts, or a mixture thereof.

### Claim 10 (depends on 1)

The method of claim 1, wherein the surface is a polytetrafluoroethylene (PTFE) surface.

### Claim 11 (depends on 1)

The method of claim 1, wherein the second tissue forming particles comprise nano-sized bone particles, micro-sized bone particles, or a mixture thereof.

### Claim 12 (depends on 1)

The method of claim 1, further comprising adding a third tissue forming material to the biocompatible structure,
wherein the third tissue forming material comprises a bioactive material, cells, or a mixture thereof
wherein the bioactive material comprises proteins, enzymes, growth factors, amino acids, bone morphogenic proteins, platelet derived growth factors, vascular endothelial growth factors, or a mixture thereof; and
wherein the cells comprise epithelial cells, neurons, glial cells, astrocytes, podocytes, mammary epithelial cells, islet cells, endothelial cells, mesenchymal cells, stem cells, osteoblast, muscle cells, striated muscle cells, fibroblasts, hepatocytes, ligament fibroblasts, tendon fibroblasts, chondrocytes, or a mixture thereof.

### Claim 13 (depends on 1)

The method of claim 1, wherein the biocompatible structure is formed with a shape conforming to a shape of an implant site.

### Claim 14 (depends on 1)

The method of claim 1, wherein each of the strips has a length of about 0.005-50 centimeter, a width of about 0.002-50 centimeter, and a thickness of about 0.001-500 millimeter, and the biocompatible structure is in a cylindrical shape or a spherical shape.