Vacuum membrane thermoformed poly-4-hydroxybutyrate medical implants

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.

1 - 16 . (canceled) 
     
     
         17 . A medical implant comprising a substrate formed of an oriented poly-4-hydroxybutyrate homopolymer, copolymer or blend, wherein the medical implant is three-dimensional, and wherein the medical implant is porous. 
     
     
         18 . The medical implant of  claim 17 , wherein the substrate undergoes less than 20% shrinkage during a thermoforming process. 
     
     
         19 . The medical implant of  claim 17 , wherein the substrate comprises monofilament fibers with a tensile strength between 300 and 1,500 MPa. 
     
     
         20 . The medical implant of  claim 17 , wherein the substrate has been heated to at least 52° C., more preferably above 60° C., but less than 110° C. 
     
     
         21 . The medical implant of  claim 17 , wherein the oriented poly-4-hydroxybutyrate homopolymer, copolymer or blend is produced by a microorganism or enzymatic process. 
     
     
         22 . The medical implant of  claim 17 , wherein the substrate is a mesh, preferably a warp knit mesh. 
     
     
         23 . The medical implant of  claim 17 , wherein the oriented poly-4-hydroxybutyrate homopolymer, copolymer or blend is made of monofilament fibers. 
     
     
         24 . The medical implant of  claim 17 , wherein the oriented poly-4-hydroxybutyrate homopolymer, copolymer or blend is made of multifilament fibers. 
     
     
         25 . The medical implant of  claim 22 , wherein the mesh has at least one 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/m 2  ±40 g/m 2 , a suture pullout strength of 5.6 Kgf±1.2 Kgf, and a burst strength of 24.5 Kg±5 Kg. 
     
     
         26 . The medical implant of  claim 17 , further comprising a nucleant, plasticizer, ceramic, bioactive agent including an antimicrobial agent, contrast agent, radiopaque marker and/or radioactive substance. 
     
     
         27 . The medical implant of  claim 17 , wherein the substrate is a woven mesh, or knitted mesh. 
     
     
         28 . The medical implant of  claim 17 , wherein the medical 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. 
     
     
         29 . The medical implant of  claim 17 , wherein the medical implant is used for repair, regeneration, or replacement of soft or hard tissues. 
     
     
         30 . The medical implant of  claim 17 , wherein the substrate does not come into contact with liquid, and remains dry during thermoforming. 
     
     
         31 . A medical implant made from a thermoform of poly-4-hydroxybutyrate homopolymer, copolymer, or blend thereof, wherein a substrate of the 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, and wherein the medical implant is porous. 
     
     
         32 . The medical implant of  claim 31 , wherein the substrate undergoes less than 20% shrinkage during a thermoforming process. 
     
     
         33 . The medical implant of  claim 31 , wherein the substrate comprises monofilament fibers with a tensile strength between 300 and 1,500 MPa. 
     
     
         34 . The medical implant of  claim 31 , wherein the substrate is a mesh, preferably a warp knit mesh. 
     
     
         35 . The medical implant of  claim 31 , wherein the medical implant is used for repair, regeneration, or replacement of soft or hard tissues. 
     
     
         36 . The medical implant of  claim 31 , wherein the substrate does not come into contact with liquid, and remains dry during thermoforming.