# US 8,771,782 B2 · Implantable medical devices

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- Number: US 8,771,782 B2
- Document ID: US8771782B2
- Status: Granted
- Kind: B2
- Application number: 13/315,902
- Filed: 2011-12-09
- Published: 2012-07-05
- Granted: 2014-07-08
- Earliest claimed: 2010-12-13
- Assignees: Enbio Limited
- Applicants: Liam O'Neill; John O'Donoghue; Joe O'Keeffe; Peter Dobbyn
- Inventors: Liam O'Neill; John O'Donoghue; Joe O'Keeffe; Peter Dobbyn
- Web page: https://patentgrep.com/patent/US8771782B2

## CPC

- A61L 31/14: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61L 27/34: Macromolecular materials
- A61L 27/38: {containing added animal cells (organs or tissue containing native cells A61L27/36)}
- A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61L 29/085: {Macromolecular materials}
- A61L 29/14: Materials characterised by their function or physical properties {, e.g. lubricating compositions}
- A61L 31/10: Macromolecular materials
- A61L 2400/18: Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
- A61L 2420/02: Methods for coating medical devices
- 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

The present invention is directed to methods for producing a coated substrate, including dissolving at least one biomolecule to form a solution; nebulizing the solution to form a liquid aerosol; combining the liquid aerosol and a plasma to form a coating; and depositing, in the absence of reactive monomers, the coating onto a substrate surface. In an aspect, the substrate can be an implantable medical device.

## Claims

### Claim 1

A method of producing a coated substrate, comprising:
dissolving at least one biomolecule in a solvent to form a solution;
nebulizing the solution to form a liquid aerosol;
introducing the liquid aerosol into a plasma; and then
exposing a substrate to the liquid aerosol and the plasma to deposit, in the absence of reactive monomers, a coating comprising the at least one biomolecule onto the substrate.

### Claim 2 (depends on 1)

The method of claim 1, wherein the plasma is a non-thermal atmospheric pressure discharge.

### Claim 3 (depends on 1)

The method of claim 1, wherein the coating comprises a coagulated biomolecule.

### Claim 4 (depends on 1)

The method of claim 1, wherein the coating comprises a material that is enzymatically biodegraded in the human body.

### Claim 5 (depends on 1)

The method of claim 1, wherein the at least one biomolecule comprises collagen.

### Claim 6 (depends on 1)

The method of claim 1, wherein the at least one biomolecule comprises a resorbable biopolymer selected from the group consisting of chitosan, fibrinogen, hylauronic acid, fibronectin, and phosphorylcholine.

### Claim 7 (depends on 1)

The method of claim 1, wherein the at least one biomolecule comprises a naturally derived biopolymer selected from the group consisting of chitosan, chitin, hyaluronan, starch, polyhydroxyalkanoates, and bacterial cellulose.

### Claim 8 (depends on 1)

The method of claim 1, wherein the at least one biomolecule comprises a protein selected from the group consisting of collagen, fibrin, fibrinogen, bone morphogenetic protein (BMP), gelatin, fibronectin, fibrulin, integrin, and insulin.

### Claim 9 (depends on 1)

The method of claim 1, wherein the at least one biomolecule comprises a polysaccharide selected from the group consisting of a-glycosaminoglycans, alginate, cellulose, chitin, chitosan, hyaluronic acid, and heparin.

### Claim 10 (depends on 1)

The method of claim 1, wherein the at least one biomolecule comprises a protein involved in blood coagulation.

### Claim 11 (depends on 1)

The method of claim 1, wherein the substrate is a medical device and is selected from the group consisting of an orthopaedic implant, a dental implant, a spinal implant, a cranial maxillofacial implant, and a bone trauma fixation implant.

### Claim 12 (depends on 1)

The method of claim 1, wherein the substrate is a medical device selected from the group consisting of a stent, an implantable pulse generator, an implantable pump, a valve, an inter-vascular device, a subdermal implant, a transdermal implant, a retinal implant, a cochlear implant, a renal lead, a renal catheter, a trauma lead, a trauma catheter, a scaffold lead, a scaffold catheter, a sensor lead, a sensor catheter, an electrical lead, and a catheter.

### Claim 13 (depends on 1)

The method of claim 1, wherein the coating further comprises at least one biological active agent selected from the group consisting of vaccines, genetic material, recombinant therapeutic proteins, enzymes, amino acids, steroids, cytokines, growth factors, vitamins, and hormones.

### Claim 14 (depends on 13)

The method of claim 13, wherein the at least one biological active agent may be the same or different than the at least one biomolecule.

### Claim 15 (depends on 1)

The method of claim 1, wherein the coating further comprises at least one pharmaceutical agent selected from the group consisting of antibiotics, anti-coagulants, anti-histamines, and anti-inflammatories.

### Claim 16 (depends on 1)

The method of claim 1, wherein the plasma is pulsed.

### Claim 17

A method of attaching living cells to a substrate surface, comprising:
introducing a liquid aerosol comprising a solution of living cells into a non-thermal plasma to form plasma-treated living cells; and
depositing the plasma-treated living cells onto the substrate surface.

### Claim 18 (depends on 17)

The method of claim 17, wherein the solution of living cells further comprises at least one biopolymer.

### Claim 19 (depends on 17)

The method of claim 17, wherein the solution of living cells is derived from a patient or from the patient's blood.

### Claim 20

A method of producing a coated substrate, comprising:
dissolving at least one biomolecule in a solvent to form a solution;
nebulizing the solution to form a liquid aerosol;
introducing the liquid aerosol into a plasma afterglow; and then
exposing a substrate to the liquid aerosol and the plasma afterglow to deposit, in the absence of reactive monomers, a coating comprising the at least one biomolecule onto the substrate.

### Claim 21

A method of producing a coated substrate, comprising:
dissolving at least one biomolecule in a solvent to form a solution, the at least one biomolecule having biological activity;
nebulizing the solution to form a liquid aerosol;
introducing the liquid aerosol into a plasma; and then
exposing a substrate to the liquid aerosol and the plasma to deposit, in the absence of reactive monomers, a coating onto the substrate;
wherein the coating retains biological activity of the at least one biomolecule.

### Claim 22

A method of producing a coated substrate, comprising:
dissolving at least one biomolecule in a solvent to form a solution;
nebulizing the solution to form a liquid aerosol;
introducing the liquid aerosol into a plasma; and then exposing a substrate to the liquid aerosol and the plasma to deposit, in the absence of reactive monomers, a coating comprising the at least one biomolecule onto the substrate, wherein the substrate is exposed to the liquid aerosol and the plasma at atmospheric pressure.
