# US 10,478,206 B2 · Instruments and methods for the implantation of cell-seeded substrates

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- Number: US 10,478,206 B2
- Document ID: US10478206B2
- Status: Granted
- Kind: B2
- Application number: 14/114,160
- Filed: 2012-04-27
- Published: 2015-01-29
- Granted: 2019-11-19
- Earliest claimed: 2011-04-29
- Assignees: University of Southern California; California Institute of Technology; The Regents of the University of California
- Applicants: Mark Humayun; Ashish Ahuja; Yu-Chong Tai; Robert Grubbs; Rodrigo Brant; Trent Wells; Lincoln Vallance Johnson; Sherry T. Hikita; David Hinton
- Inventors: Mark Humayun; Ashish Ahuja; Yu-Chong Tai; Robert Grubbs; Rodrigo Brant; Trent Wells; Lincoln Vallance Johnson; Sherry T. Hikita; David Hinton
- Web page: https://patentgrep.com/patent/US10478206B2

## CPC

- A61B 17/2909: {Handles}
- A61F 2/14: Eye parts, e.g. lenses or corneal implants; Artificial eyes
- A61F 2/4601: {for introducing bone substitute, for implanting bone graft implants or for compacting them in the bone cavity}
- A61F 9/0017: {implantable in, or in contact with, the eye, e.g. ocular inserts}
- A61F 9/007: Methods or devices for eye surgery
- A61F 9/00736: {Instruments for removal of intra-ocular material or intra-ocular injection, e.g. cataract instruments (A61F9/008 takes precedence)}
- A61K 35/50: Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
- A61L 27/16: obtained by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/34: Macromolecular materials
- A61L 27/3813: {Epithelial cells, e.g. keratinocytes, urothelial cells}
- A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61M 5/14: Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- C12N 5/0621: {Eye cells, e.g. cornea, iris pigmented cells (photoreceptors C12N5/062)}
- A61B 2017/2937: {with flexible part}
- A61B 2017/2945: {Curved jaws}
- A61B 2017/305: {Tweezer like handles with tubular extensions, inner slidable actuating members and distal tools, e.g. microsurgical instruments}
- A61L 2430/16: for reconstruction of eye parts, e.g. intraocular lens, cornea
- A61M 2202/09: Body tissue
- C12N 2506/02: from embryonic cells
- C12N 2533/30: Synthetic polymers
- C12N 2533/40: Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
- C12N 2533/50: Proteins
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- 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)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- 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)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Disclosed herein are instruments and methods for delivery of substrates, including cell-seeded substrates, to target tissues requiring treatment for various diseases that induce cell death, damage or loss of function. The substrates are configured to provide cells, including stem cells, with a structural support that allows interconnection with and transmission of biological signals between the cells and the target tissue.

## Claims

### Claim 1

An instrument for an implantation of a substrate into a target tissue of a subject, comprising:
a handpiece comprising a proximal end and a distal end, said distal end comprising an orifice;
an outer housing extending in a distal direction from said handpiece, a distal end of the outer housing terminating in a bevel;
an internal shaft configured to be longitudinally moveable within said outer housing and said handpiece;
forceps connected with the internal shaft;
a shaft movement control mechanism; and
a planar substrate having a tail and a body of a same thickness as the tail,
wherein activation of said movement control mechanism causes longitudinal movement of said internal shaft and forceps;
wherein movement of said internal shaft in a proximal direction is configured to cause said forceps to grasp the tail of the substrate, induce a rolling of the substrate against the bevel of said outer housing, and retract the substrate within said outer housing, and
wherein movement of said internal shaft in a distal direction is configured to cause the substrate to exit said outer housing and unroll and cause said forceps to open.

### Claim 2 (depends on 1)

The instrument of claim 1, wherein said movement control mechanism comprises a slide mechanism.

### Claim 3 (depends on 1)

The instrument of claim 1, wherein said movement control mechanism comprises a friction wheel mechanism.

### Claim 4 (depends on 1)

The instrument of claim 1, wherein said movement control mechanism comprises one or more racks associated with said forceps and a gear mechanism that interacts with said racks.

### Claim 5 (depends on 1)

The instrument of claim 1, further comprising an injection pathway.

### Claim 6 (depends on 5)

The instrument of claim 5, wherein said injection pathway is configured to deliver a media from the handpiece to a target site at or near a distal-most portion of the internal shaft.

### Claim 7 (depends on 1)

The instrument of claim 1, further comprising:
a substrate support platform with which said forceps are configured to reversibly interact.

### Claim 8 (depends on 7)

The instrument of claim 7, wherein after interacting with the substrate support platform, proximal longitudinal movement of the movement control mechanism is configured to retract the internal shaft resulting in contact between outer edges of the substrate support platform and an inner portion of the outer housing, thereby inducing the substrate support platform to roll into a cylindrical shape.

### Claim 9 (depends on 8)

The instrument of claim 8, wherein distal longitudinal movement of the movement control mechanism causes the outer edges of the substrate support platform to move distally beyond the outer housing, thereby allowing the rolled support platform to unroll.

### Claim 10 (depends on 1)

The instrument of claim 1, wherein the substrate has a curved region between the tail and the body.

### Claim 11 (depends on 10)

The instrument of claim 10, wherein a length of the tail is between 1 mm and 20 mm.

### Claim 12 (depends on 11)

The instrument of claim 11, wherein a length of the tail is between 1 mm and 2 mm.

### Claim 13 (depends on 1)

The instrument of claim 1, wherein a width of the tail is between 0.2 mm and 6 mm.

### Claim 14

An instrument for an implantation of a substrate into a target tissue of a subject, comprising:
a handpiece comprising a proximal end and a distal end, said distal end comprising an orifice;
an outer housing extending in a distal direction from said handpiece, a distal end of the outer housing terminating in a bevel;
an internal shaft configured to be longitudinally moveable within said outer housing and said handpiece;
forceps connected with the internal shaft;
a shaft movement control mechanism; and
an injection pathway within the outer housing,
wherein activation of said movement control mechanism causes longitudinal movement of said internal shaft and forceps;
wherein movement of said internal shaft in a proximal direction is configured to cause said forceps to grasp a tail of the substrate, induce a rolling of the substrate against the bevel of said outer housing, and retract the substrate within said outer housing, and
wherein movement of said internal shaft in a distal direction is configured to cause the substrate to exit said outer housing and unroll and cause said forceps to open.

### Claim 15 (depends on 14)

The instrument of claim 14, further comprising:
a substrate having a tail, a body, and a curved region between the tail and the body.

### Claim 16 (depends on 14)

The instrument of claim 14, wherein said movement control mechanism comprises a slide mechanism.

### Claim 17 (depends on 14)

The instrument of claim 14, wherein said movement control mechanism comprises a friction wheel mechanism.
