# US 10,369,253 B2 · Method for modifying surfaces for better osseointegration

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- Number: US 10,369,253 B2
- Document ID: US10369253B2
- Status: Granted
- Kind: B2
- Application number: 14/355,051
- Filed: 2012-10-31
- Published: 2014-10-16
- Granted: 2019-08-06
- Earliest claimed: 2011-10-31
- Assignees: The University of Toledo
- Applicants: The University of Toledo
- Inventors: Sarit B. Bhaduri; Vijay K. Goel; Huan Zhou
- Web page: https://patentgrep.com/patent/US10369253B2

## CPC

- A61L 27/32: Phosphorus-containing materials, e.g. apatite
- A61L 27/00: Materials for {grafts or} prostheses or for coating {grafts or} prostheses (dental prostheses A61C13/00; shape or structure of prostheses A61F2/00; use of preparations for artificial teeth A61K6/80; artificial kidneys A61M1/14)
- A61L 27/12: Phosphorus-containing materials, e.g. apatite
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 29/106: {Inorganic materials other than carbon}
- A61L 31/086: {Phosphorus-containing materials, e.g. apatite}
- 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
- 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)

## Abstract

In one aspect, there is provided a method for preparing a biocompatible coated substrate. The method generally includes: depositing nucleation amorphous calcium phosphate sites on at least a portion of an outer surface of a substrate by: exposing at least the portion of the outer surface to a mixture having a favorable Ca/P molar ratio, and irradiating with microwave energy; and, stabilizing the deposited nucleation amorphous calcium phosphate sites on the portion of the outer surface. In another aspect, there is provided herein a method for preparing a biocompatible coated substrate.

## Claims

### Claim 1

A method for preparing a biocompatible coated substrate comprising:
pretreating at least a portion of a substrate by etching the substrate with NaOH so as to activate a surface of the portion of the substrate, wherein the portion of the substrate comprises a polymeric material comprising polyetheretherketone (PEEK);
exposing the surface to a solution mixture comprising at least calcium and phosphate ions at a Ca/P molar ratio of from about 1 to about 2.5, wherein the calcium and phosphate ions are present in the solution mixture at a concentration on the order of a millimolar concentration;
exposing the solution mixture and the portion of the substrate to microwave energy for a time sufficient to form a calcium phosphate (CaP) layer having a thickness of about 15 μm or less on the surface, wherein the sufficient time is about 1 hour or less; and
keeping the substrate in ethanol for a period of time to stabilize the CaP layer on the surface.

### Claim 2 (depends on 1)

The method of claim 1, wherein the CaP layer is configured to allow for release of calcium and phosphate ions, and for triggering local formation of bone-like apatite on the surface.

### Claim 3 (depends on 1)

The method of claim 1, wherein the mixture has a Ca/P molar ratio of at least about 1 to about 1.7.

### Claim 4 (depends on 1)

The method of claim 1, wherein the solution mixture includes silica.

### Claim 5 (depends on 4)

The method of claim 4, wherein the silica comprises nanocrystalline and/or colloidal silica.

### Claim 6 (depends on 1)

The method of claim 1, wherein the solution mixture and the portion of the substrate are exposed to microwave energy for about 45 minutes or less, or about 30 minutes or less.

### Claim 7 (depends on 1)

The method of claim 1, wherein the substrate comprises one or more of: an implantable device, a dental implant, an orthopedic implant, a medical device, a pacemaker, an artificial organ, a heart, medical tubing, a catheter, a feeding tube, a surgical drain, a surgical pump, or dialysis devices.

### Claim 8 (depends on 1)

The method of claim 1, wherein the CaP layer has an overall thickness of about 10 μm or less.

### Claim 9 (depends on 1)

The method of claim 1, wherein the CaP layer has a thickness of about 5 μm or less.

### Claim 10 (depends on 1)

The method of claim 1, wherein the CaP layer covers the portion of the substrate.

### Claim 11 (depends on 1)

The method of claim 1, wherein the CaP layer further includes one or more biologically or pharmaceutically active compounds.

### Claim 12 (depends on 11)

The method of claim 11, wherein the pharmaceutically active compound is a cell growth factor and/or a bone morphogenetic protein.

### Claim 13 (depends on 1)

The method of claim 1, wherein the CaP layer further includes one or more of: materials for facilitating bio-ingrowth between the substrate and bone, or cartilage tissue.