# US 11,298,440 B2 · Microstructured haptotaxic implant

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- Number: US 11,298,440 B2
- Document ID: US11298440B2
- Status: Granted
- Kind: B2
- Application number: 17/236,738
- Filed: 2021-04-21
- Published: 2021-09-23
- Granted: 2022-04-12
- Earliest claimed: 2016-04-30
- Assignees: BVW Holding AG
- Applicants: BVW Holding AG
- Inventors: Lukas Bluecher; Michael Milbocker
- Web page: https://patentgrep.com/patent/US11298440B2

## CPC

- A61L 27/26: Mixtures of macromolecular compounds
- A61F 2/0077: {Special surfaces of prostheses, e.g. for improving ingrowth (A61F2/30767 takes precedence)}
- A61L 27/48: with macromolecular 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 27/56: Porous materials, {e.g. foams or sponges}
- A61L 27/58: Materials at least partially resorbable by the body
- A61L 31/14: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61F 2/0063: {Implantable repair or support meshes, e.g. hernia meshes}
- 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)}
- A61F 2002/0081: {directly machined on the prosthetic surface, e.g. holes, grooves (A61F2/30771 takes precedence)}
- A61F 2002/0086: {for preferentially controlling or promoting the growth of specific types of cells or tissues}
- A61F 2250/0031: made from both resorbable and non-resorbable prosthetic parts, e.g. adjacent parts
- A61F 2250/0056: differing in wettability, e.g. in hydrophilic or hydrophobic behaviours
- A61L 2400/12: Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
- 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

The invention relates to the field of tissue engineering and regenerative medicine, and particularly to a three-dimensional biomimetic tissue scaffold that exploits the use of three-dimensional print technology. Surface energy is controlled by precisely placing polymers with differing surface chemistry, and using surface texture and bulk composition to pattern absorbable and non-absorbable polymers for the purpose of promoting functional healing in a mammalian body.

## Claims

### Claim 1

A three-dimensional matrix for tissue regeneration comprising at least three successive layers of at least two biocompatible polymers that are solid at temperature below 36° C., the layers arranged to form walls with open voids therebetween, the voids suitable for seeding or ingrowth of cells, the layers comprising a first polymer and a second polymer, the first or second polymer comprising polyester urethane, polyether urethane or a combination thereof, and wherein the first and second polymers are disposed in an alternating pattern along at least one axis of the matrix, wherein the first polymer is hydrophobic and/or lipophilic and the second polymer is hydrophilic; and
wherein the matrix has a surface energy, the surface energy being varied on at least three spatial scales comprising 1) a macro scale ranging from 50 micron to 1 mm obtained by forming layers of polymers of different surface energy, 2) a meso scale ranging from 1 micron to 50 micron obtained by placing a surface pattern on the polymers, and 3) a fine-scale of less than 1 micron obtained by variation of molecular structure.

### Claim 2 (depends on 1)

The matrix of claim 1, wherein the first and second polymers are nanofibers.

### Claim 3 (depends on 1)

The matrix of claim 1, wherein the walls intersect at junctions along the first axes and second axes, the first axes being parallel first axes, and wherein the walls comprise alternating layers of the first and second polymers along second axes are perpendicular to the first axes.

### Claim 4 (depends on 1)

The matrix of claim 1, wherein the matrix is formed on an implantable substrate.

### Claim 5 (depends on 4)

The matrix of claim 4, wherein the implantable substrate and the matrix are bioabsorbable, and wherein the implantable substrate bioabsorbs more rapidly than the matrix.

### Claim 6 (depends on 1)

The matrix of claim 1, wherein the three-dimensional matrix further comprises a bioactive agent.

### Claim 7 (depends on 2)

The matrix of claim 2, wherein the nanofibers include a diameter from 100 nm to 5 microns.

### Claim 8 (depends on 2)

The matrix of claim 2, wherein the nanofibers include a diameter from 100 nm to 500 microns.

### Claim 9 (depends on 1)

The matrix of claim 1, wherein the at least first polymer comprises polypropylene, polycaprolactone, polylactic acid, or combinations thereof.

### Claim 10 (depends on 1)

The matrix of claim 1, wherein the at least second polymer comprises polyether urethane, polyester urethane, polyhyaluronic acid, or combinations thereof.

### Claim 11 (depends on 10)

The matrix of claim 10, wherein the at least second polymer comprises polyether urethane, polyester urethane, polyhyaluronic acid, or combinations thereof.

### Claim 12

A three-dimensional matrix for tissue regeneration comprising:
a substrate having at least three successive layers of at least two biocompatible polymers that are solid at temperature below 36° C., the layers arranged to form walls with open voids therebetween, the voids suitable for seeding or ingrowth of cells, the layers comprising a first polymer and a second polymer, comprising polyester urethane, polyether urethane or a combination thereof, and wherein the first and second polymers are disposed in an alternating pattern along at least one axis of the matrix, wherein the first polymer is hydrophobic and/or lipophilic and the second polymer is hydrophilic;
an implantable layer wherein the substrate is disposed on the implantable layer; and
wherein the matrix has a surface energy, the surface energy being varied on at least three spatial scales comprising 1) a macro scale ranging from 50 micron to 1 mm obtained by forming layers of polymers of different surface energy, 2) a meso scale ranging from 1 micron to 50 micron obtained by placing a surface pattern on the polymers, and 3) a fine-scale of less than 1 micron obtained by variation of molecular structure.

### Claim 13 (depends on 12)

The matrix of claim 12, wherein the first and second polymers are nanofibers.

### Claim 14 (depends on 12)

The matrix of claim 12, wherein the walls intersect at junctions along parallel first axes, and wherein the walls comprise alternating layers of the first and second polymers along second axes perpendicular to the first axes.

### Claim 15 (depends on 12)

The matrix of claim 12, wherein the substrate and the implantable layer are bioabsorbable, and wherein the implantable layer bioabsorbs more rapidly than the substrate.

### Claim 16 (depends on 12)

The matrix of claim 12, wherein the three-dimensional matrix further comprises a bioactive agent.

### Claim 17 (depends on 13)

The matrix of claim 13, wherein the nanofibers include a diameter from 100 nm to 5 microns.

### Claim 18 (depends on 13)

The matrix of claim 13, wherein the nanofibers include a diameter from 100 nm to 500 microns.

### Claim 19 (depends on 12)

The matrix of claim 12, wherein the at least first polymer comprises polypropylene, polycaprolactone, polylactic acid, or combinations thereof.

### Claim 20 (depends on 12)

The matrix of claim 12, wherein the at least second polymer comprises polyether urethane, polyester urethane, polyhyaluronic acid, or combinations thereof.