Medical Devices and Applications of Polyhydroxyalkanoate Polymers

Abstract

Devices formed of or including biocompatible polyhydroxyalkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats. The polyhydroxyalkanoates can contain additives, be formed of mixtures of monomers or include pendant groups or modifications in their backbones, or can be chemically modified, all to alter the degradation rates. The polyhydroxyalkanoate compositions also provide favorable mechanical properties, biocompatibility, and degradation times within desirable time frames under physiological conditions.

1 - 34 . (canceled)  
   
   
       35 . A biodegradable composition comprising a poly-4-hydroxybutyrate that has a controlled degradation rate, under physiological conditions, wherein the degradation rate of the polymer is manipulated through the addition of components to the polymer, selection of the molecular weight of the polymer, or form of the composition, and wherein the polymer has a weight average molecular weight of between 10,000 and 10,000,000.  
   
   
       36 . The composition of  claim 35 , wherein the chemical composition of the poly-4-hydroxybuyrate composition is altered through selection of monomers which are incorporated into the polymer, by alteration of the linkages, chemical backbone or pendant groups, or by manipulation of the molecular weight.  
   
   
       37 . The composition of  claim 35 , wherein the poly-4-hydroxybutyrate composition comprises additives altering the degradation rate of the composition, wherein the additives are selected from the group consisting of hydrophilic substances, hydrophobic substances, and coating which alter water uptake by the composition.  
   
   
       38 . The composition of  claim 35 , wherein the poly-4-hydroxybutyrate composition comprises a polymer selected from the group of consisting of poly-4-hydroxybutyrate, poly-4-hydroxybutyrate-co-3-hydroxybutyrate, poly-4-hydroxybutyrate-co-2-hydroxybutyrate, and copolymers and blends thereof.  
   
   
       39 . The composition of  claim 35  wherein the poly-4-hydroxybutyrate composition comprises one or more units which alter the chemical stability of the polymer backbone.  
   
   
       40 . The composition of  claim 39  comprising unit(s) promoting chain scission.  
   
   
       41 . The composition of  claim 40 , wherein the units contain more than two functional groups.  
   
   
       42 . The composition of  claim 41 , wherein the units are selected from the group consisting of 2-hydroxyacids, 2-hydroxyalkoxyacetic acids, amino acids, amino alcohols, diacids, triols, and tetraols.  
   
   
       43 . The composition of  claim 42 , wherein the 2-hydroxyalkanoic acid is lactic acid or glycolic acid.  
   
   
       44 . The composition of  claim 42 , wherein the units are 2-hydroxyalkoxyacetic acids selected from the group consisting of 2-hydroxyethoxy acetic acid and 3-hydroxypropoxy acetic acid.  
   
   
       45 . The composition of  claim 35 , wherein the polymer comprises pendant groups that catalyze the degradation of the polymer backbone.  
   
   
       46 . The composition of  claim 35  comprising additives altering the chemical stability of the poly-4-hydroxybutyrate composition.  
   
   
       47 . The composition of  claim 46 , wherein the additives promote chain scission.  
   
   
       48 . The composition of  claim 47 , wherein the additives are selected from the group consisting of acids, bases, electrophiles, nucleophiles, plasticizers, polymers, pore forming agents, and agents designed to reduce the polymer crystallinity.  
   
   
       49 . The composition of  claim 35  comprising pore forming agents.  
   
   
       50 . The composition of  claim 35  further comprising one or more active agents.  
   
   
       51 . The composition of  claim 50 , wherein the active agent is selected from the group consisting of growth factors, alginates, silver salts, antiseptics, analgesics, and preservatives.  
   
   
       52 . A device comprising the biodegradable composition of  claim 35 , wherein the device is selected from the group consisting of sutures, suture fasteners, meniscus repair devices, rotator cuff repair devices, temporary wound support devices, bladder patches, pledgets, soft tissue reinforcement, devices, vascular patches, devices for atrial wall repair, bone marrow scaffolds, ligament repair devices, rods, washers, screws, pins, stuts, plates and staples used in spinal fusion cages, rivets, tacks, staples, screws, bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins, adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, sewing rings, stiffeners used in heart valve supports, cell encapsulation devices, coated devices, defect filling devices, organ patches, organ salvage devices, staple line reinforcement devices, pelvic floor reconstruction devices, devices for closure of ventricular septal defects, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, heart valves, vascular grafts, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats, and drug delivery devices.  
   
   
       53 . The device of  claim 52 , wherein the chemical composition of the poly-4-hydroxybuyrate composition is altered through selection of monomers which are incorporated into the polymer, or by alteration of the linkages, chemical backbone or pendant groups.  
   
   
       54 . The device of  claim 52 , wherein the poly-4-hydroxybuyrate composition comprises additives altering the degradation rate of the composition, wherein the additives are selected from the group consisting of hydrophilic substances, hydrophobic substances, and coating which alter water uptake by the composition.  
   
   
       55 . The device of  claim 52 , wherein the poly-4-hydroxybuyrate composition comprises a polymer selected from the group of consisting of poly-4-hydroxybutyrate, poly-4-hydroxybutyrate-co-3-hydroxybutyrate, poly-4-hydroxybutyrate-co-2-hydroxybutyrate, and copolymers and blends thereof.  
   
   
       56 . The device of  claim 52 , wherein the poly-4-hydroxybuyrate composition comprises one or more units which alter the chemical stability of the polymer backbone.  
   
   
       57 . The device of  claim 56 , comprising units promoting chain scission.  
   
   
       58 . The device of  claim 57 , wherein the units are incorporated into the polymer backbone with chemical linkages selected from the group consisting of ester, amide, ether, carbamate, anhydride, and carbonate.  
   
   
       59 . The device of  claim 56 , wherein the units are selected from the group consisting of 2-hydroxyacids, 2-hydroxyalkaoxyacetic acids, amino acids, amino alcohols, diacids, triols, and tetraols.  
   
   
       60 . The device of  claim 52 , wherein the polymer comprises pendant groups that catalyze the degradation of the polymer backbone.  
   
   
       61 . The device of  claim 52 , comprising providing additives altering the chemical stability of the polyhydroxyalkanoate.  
   
   
       62 . The device of  claim 61 , wherein the additives promote chain scission.  
   
   
       63 . The device of  claim 61 , wherein the additives are selected from the group consisting of acids, bases, electrophiles, nucleophiles, plasticizers, polymers, pore forming agents, and agents designed to reduce the polymer crystallinity.  
   
   
       64 . The device of  claim 63  comprising providing pore forming agents.  
   
   
       65 . The device of  claim 52 , further comprising one or more active agents.  
   
   
       66 . The device of  claim 65 , wherein the active agent is selected from the group consisting of growth factors, alginates, silver salts, antiseptics, analgesics, and preservatives.  
   
   
       67 . The device of  claim 52 , wherein the device is a drug delivery device and the drug is selected from the group consisting of biological factors, antibodies, enzymes, antigens, inhibitors, clot dissolving agents, and hormones.  
   
   
       68 . The device of  claim 67 , wherein the device is a drug delivery device and the drug is selected from the group consisting of proteins, peptides, polysaccharides, organic drugs, inorganic drugs, nucleic acids, and lipids.