Protein biomaterials and biocoacervates and methods of making and using thereof
The present invention relates to protein biocoacervates and biomaterials and the methods of making and using protein biocoacervates and biomaterials. More specifically the present invention relates to protein biocoacervates and biomaterials that may be utilized for various medical applications including, but not limited to, drug delivery devices for the controlled release of pharmacologically active agents, coated medical devices (e.g. stents, valves . . . ), vessels, tubular grafts, vascular grafts, wound healing devices including protein suture biomaterials and biomeshes, dental plugs and implants, skin/bone/tissue grafts, tissue fillers, protein biomaterial adhesion prevention barriers, cell scaffolding and other biocompatible biocoacervate or biomaterial devices.
1. An amorphous biomaterial comprising an amorphous biocoacervate material that is crosslinked with one or more crosslinking agents, the amorphous biocoacervate material including aggregated complexes having homogenously distributed biocoacervated components, the components comprising one or more soluble or solubilized primary proteins combined with one or more glycosaminoglycans and one or more biocompatible solvents, wherein the amorphous biocoacervate material is thermoplastic prior to being crosslinked with the one or more crosslinking agents.
2. The amorphous biomaterial of claim 1 wherein the one or more primary proteins are selected from the group consisting of collagen, laminin, bone morphogenic protein and its isoforms that contain glycosaminoglycan binding sites, albumin, interleukins, epidermal growth factors, fibronectin, thrombin, aprotinin and antithrombin III.
3. The amorphous biomaterial of claim 1 wherein the one or more glycosaminoglycans are selected from the group consisting of heparin, heparin sulfate, keratan sulfate, dermatin, dermatin sulfate, heparin-hyaluronic acid, chondroitin, chondroitin sulfate, chondroitin 6-sulfate, chondroitin 4-sulfate, chitin, chitosan, acetyl-glucosamine, hyaluronic acid, aggrecan, decorin, biglycan, fibromodulin, lumican and complexes thereof.
4. The amorphous biomaterial of claim 1 further comprising one or more secondary proteins.
5. The amorphous biomaterial of claim 4 wherein the one or more secondary proteins are selected from the group consisting of fibrin, fibrinogen, elastin, albumin, ovalbumin, keratin, silk, silk fibroin, actin, myosin, thrombin, aprotinin and antithrombin III.
6. The amorphous biomaterial of claim 1 wherein the one or more biocompatible solvents are selected from the group consisting of water, dimethyl sulfoxide (DMSO), biocompatible alcohols, biocompatible acids, oils and biocompatible glycols.
7. The amorphous biomaterial of claim 1 further comprising one or more pharmacologically active agents.
8. The amorphous biomaterial of claim 7 wherein the one or more pharmacologically active agents are selected from the group consisting of analgesics, anesthetics, antiproliferative agents, angiogenesis inhibitors, antipsychotic agents, angiogenic growth factors, bone mending biochemicals, steroids, antisteroids, corticosteroids, antiglacoma agents, antialcohol agents, anti coagulant agents, antithrombolytic agents, anticancer agents, anti Parkinson agents, antiepileptic agents, anti inflammatory agents, anticonception agents, enzyme agents, cells, growth factors, antiviral agents, antibacterial agents, antifungal agents, hypoglycemic agents, antihistamine agents, chemoattractants, neutraceuticals, antiobesity, smoking cessation agents, obstetric agents and antiasmatic agents.
9. The amorphous biomaterial of claim 7 wherein the one or more pharmacologically active agents are selected from the group consisting of paclitaxol, sirolimus, estradiol, demopressin, dexamethazone, bone morphogenic protein, vitamin D, vitamin E, vitamin A, vitamin C, vitamin B, stem cells, superoxide dismutase, VEGF, FGF, EGF, sufentanil, fentanyl, capsaicin, lidocaine bupivacaine, benzocaine, testosterone and cortisone.
10. The amorphous biomaterial of claim 1 wherein the biomaterial further includes one or more biocompatible additives selected from the group consisting of epoxies, polyesters, acrylics, nylons, silicones, polyanhydride, polyurethane, polycarbonate, poly(tetrafluoroethylene), polycaprolactone, polyalkenes, polyacrylates, bioceramic materials, polyethylene oxide, polyethylene glycol, poly(vinyl chloride), polylactic acid, polyglycolic acid, polypropylene oxide, poly(alkylene)glycol, polyoxyethylene, sebacic acid, polyvinyl alcohol, 2 hydroxyethyl methacrylate, polymethyl methacrylate, 1,3 bis(carboxyphenoxy)propane, lipids, phosphatidylcholine, triglycerides, polyhydroxybutyrate, polyhydroxyvalerate, poly(ethylene oxide), poly ortho esters, poly (amino acids), polycyanoacrylates, polyphophazenes, polysulfone, polyamine, poly (amido amines), glycosaminoglycans, bioceramic materials, insoluble proteins, proteins, amino acids, oils, fatty acids, salts, sugars, polypeptides, peptides, humectants, fibrin, graphite, flexible fluoropolymer, isobutyl based, isopropyl styrene, vinyl pyrrolidone, cellulose acetate dibutyrate, silicone rubber, and copolymers of these.
11. The amorphous biomaterial of claim 1 wherein the biomaterial further includes one or more additives selected from the group consisting of hyaluronic acid, chondroitin sulfate, glycine, glutamine, calcium carbonate, calcium sulfate, magnesium sulfate, glucose, ribose, alginate, collagen, elastin, laminin, hydroxyapatite, polyethylene glycol, glycerol, sodium hydroxide and potassium hydroxide.
12. The amorphous biomaterial of claim 1 wherein the one or more crosslinking agents are selected from the group consisting of glutaraldehyde, 1,4-butandiol diglycidylether, formaldehyde, glyoxal, sebacic acid bis(N-succinimidyl)ester (DSS), p Azidobenzolyl Hydazide, N 5 Azido 2 nitrobenzoyloxysuccinimide, N Succinimidyl 6 [4′azido 2′nitro phenylamino]hexanoate and 4 [p Azidosalicylamido]butylamine.
13. The amorphous biomaterial of claim 1 wherein the biomaterial is processed in a form selected from the group consisting of a coating, cylinder, wafer, bar, sphere, capsule, vessel, tubular graft, particles, biomesh, plug, sheet and valve.
14. The amorphous biomaterial of claim 4 wherein the primary proteins include collagen, the glycosaminoglycan is selected from the group consisting of hyaluronic acid, heparin and condroitin sulfate, the secondary proteins include elastin and the biocompatible solvent includes water.