# US 2019/0167834 A1 · Vacuum membrane thermoformed poly-4-hydroxybutyrate medical implants

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- Number: US 2019/0167834 A1
- Document ID: US20190167834A1
- Status: Published application
- Kind: A1
- Application number: 16/209,299
- Filed: 2018-12-04
- Published: 2019-06-06
- Earliest claimed: 2017-12-04
- Assignees: Tepha, Inc.
- Applicants: Tepha, Inc.
- Inventors: David P. Martin; Said Rizk
- Web page: https://patentgrep.com/patent/US20190167834A1

## CPC

- A61L 15/26: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof {(A61L15/225 takes precedence)}
- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/48: with macromolecular fillers
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 29/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 29/126: {having a macromolecular matrix}
- A61L 31/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)}
- A61L 31/126: {containing carbon fillers}
- A61L 31/129: {containing macromolecular fillers}
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- B29C 51/002: {characterised by the choice of material}
- B29C 51/421: {of preforms, specially adapted for thermoforming (preheating sheets in general B29B13/023; B29C51/427 takes precedence)}
- B29C 51/10: Forming by pressure difference, e.g. vacuum
- B29C 2791/006: Using vacuum
- B29L 2031/753: {Medical equipment; Accessories therefor (bloodbags, medical bags B29L2031/7148; artificial eyes B29L2011/0008)}
- B29L 2031/7532: {Artificial members, protheses}
- 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)
- B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00)
- B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES

## Abstract

Methods to produce thermoformed implants comprising poly-4-hydroxybutyrate homopolymer, copolymer, or blend thereof, including surgical meshes, have been developed. These thermoforms are preferably produced from porous substrates of poly-4-hydroxybutyrate homopolymer or copolymer thereof, such as surgical meshes, by vacuum membrane thermoforming. The porous thermoformed implant is formed by placing a porous substrate of poly-4-hydroxybutyrate homopolymer or copolymer thereof over a mold, covering the substrate and mold with a membrane, applying a vacuum to the membrane so that the membrane and substrate are drawn down on the mold and tension is applied to the substrate, and heating the substrate while it is under tension to form the thermoform. The method is particularly useful in forming medical implants of poly-4-hydroxybutyrate and copolymers thereof, including hernia meshes, mastopexy devices, breast reconstruction devices, and implants for plastic surgery, without exposing the resorbable implants to water and without shrinking the porous substrate during molding.

## Claims

### Claim 1

A medical implant made from a thermoform of poly-4-hydroxybutyrate homopolymer, copolymer, or blend thereof, wherein a substrate of poly-4-hydroxybutyrate homopolymer, copolymer or blend has been placed on a mold, covered by an impermeable flexible membrane, drawn down onto the mold by applying a vacuum, heated under tension, allowed to cool, released from the vacuum, and removed from the mold.

### Claim 2 (depends on 1)

The implant of claim 1 wherein the substrate has been heated to at least 52° C., more preferably above 60° C., but less than 110° C.

### Claim 3 (depends on 1)

The implant of claim 1 wherein the poly-4-hydroxybutyrate homopolymer or copolymer is produced by a microorganism or enzymatic process.

### Claim 4 (depends on 1)

The implant of claim 1 wherein the substrate is porous.

### Claim 5 (depends on 4)

The implant of claim 4 wherein the substrate is a mesh, preferably a warp knit mesh and optionally, a polymeric film is not drawn into the pores of the mesh.

### Claim 6 (depends on 5)

The implant of claim 5 wherein the mesh is made of oriented monofilament fibers.

### Claim 7 (depends on 6)

The implant of claim 6 wherein the mesh has one or more of the following properties: an average pore diameter of approximately 500 μm±100 μm, a thickness of 0.5 mm±0.1 mm, an areal density of 182 g/m2±40 g/m2, a suture pullout strength of 5.6 Kgf±1.2 Kgf, and a burst strength of 24.5 Kg±5 Kg.

### Claim 8 (depends on 1)

The implant of claim 1 wherein the implant further comprises a nucleant, plasticizer, ceramic, bioactive agent including an antimicrobial agent, contrast agent, radiopaque marker and/or radioactive substance.

### Claim 9 (depends on 1)

The implant of claim 1 wherein the implant is a woven mesh, or knitted mesh.

### Claim 10 (depends on 1)

The implant of claim 1 wherein the implant is selected from the group consisting of patches, wound healing device, bandage, wound dressing, burn dressing, ulcer dressing, skin substitute, hemostat, tracheal reconstruction device, organ salvage device, pledgets, dural substitute, dural patch, nerve guide, nerve regeneration or repair device, hernia repair device, hernia mesh, hernia plug, device for temporary wound or tissue support, tissue engineering scaffold, guided tissue repair/regeneration device, laminated knitted, woven and non-woven meshes, fixation devices for meshes, anti-adhesion membrane, adhesion barrier, tissue separation membrane, retention membrane, catheter, sling, device for pelvic floor reconstruction, urethral suspension device, device for treatment of urinary incontinence, device for treatment of vesicoureteral reflux, bladder repair device, sphincter muscle repair device, bulking or filling device, bone marrow scaffold, clip, clamp, screw, pin, locking pin, nail, tube, medullary cavity nail, bone plate, interference screw, tack, arrow, fastener, rivet, staple, fixation device for an implant, bone graft substitute, bone void filler, suture anchor, bone anchor, ligament repair device, ligament augmentation device, ligament graft, anterior cruciate ligament repair device, tendon repair device, tendon graft, tendon augmentation device, rotator cuff repair device, meniscus repair device, meniscus regeneration device, articular cartilage repair device, osteochondral repair device, spinal fusion device, vertebral disc, cage, device for treatment of osteoarthritis, viscosupplement, stent, including coronary, cardiovascular, peripheral, ureteric, urethral, urology, gastroenterology, nasal, ocular, or neurology stents and stent coatings, stent graft, cardiovascular patch, catheter balloon, vascular closure device, intracardiac septal defect repair device, including but not limited to atrial septal defect repair devices and PFO (patent foramen ovale) closure devices, left atrial appendage (LAA) closure device, pericardial patch, vein valve, heart valve, vascular graft, myocardial regeneration device, periodontal mesh, guided tissue regeneration membrane for periodontal tissue, ocular cell implant, imaging device, cochlear implant, embolization device, anastomosis device, cell seeded device, cell encapsulation device, controlled release device, drug delivery device, plastic surgery device, breast lift device, mastopexy device, breast reconstruction device, breast augmentation device (including devices for use with breast implants), breast reduction device (including devices for removal, reshaping and reorienting breast tissue), devices for breast reconstruction following mastectomy with or without breast implants, facial reconstructive device, forehead lift device, brow lift device, eyelid lift device, face lift device, buttock lift device, thigh lift device, arm lift device, rhytidectomy device, thread lift device (to lift and support sagging areas of the face, brow and neck), rhinoplasty device, device for malar augmentation, otoplasty device, neck lift device, mentoplasty device, cosmetic repair device, and device for facial scar revision.

### Claim 11 (depends on 10)

The implant of claim 10 wherein the implant is used for the repair, regeneration, or replacement of soft or hard tissues.

### Claim 12 (depends on 1)

A method of making the implant of claim 1 by vacuum membrane thermoforming comprising placing a substrate of poly-4-hydroxybutyrate homopolymer, copolymer or blend thereof on a mold, covering the substrate with an impermeable flexible membrane, drawing down the substrate onto the mold by applying a vacuum, heating the substrate under tension, allowing the thermoform to cool, releasing the thermoform from the vacuum, and removing the thermoform from the mold.

### Claim 13 (depends on 12)

The method of claim 12, wherein the substrate is heated to at least 52° C., more preferably above 60° C., but less than 110° C.

### Claim 14 (depends on 12)

The method of claim 12, wherein the substrate is an oriented monofilament poly-4-hydroxybutyrate mesh.

### Claim 15 (depends on 12)

The method of claim 12, wherein the substrate does not come into contact with liquid, and remains dry during thermoforming.

### Claim 16 (depends on 1)

A method of using the implants of claim 1, wherein the implants are used for the repair, regeneration, or replacement of soft or hard tissues.