Naso-pharyngeal tissue engineering
Methods to stiffen nasopharyngeal structures such as the soft palate, the anterior palatine arch, the posterior palatine arch, or a combination thereof are provided. In one embodiment, the present invention involves the injection, through a conventional needle, of PMMA microspheres that induce a fibrotic response to strengthen and stiffen nasopharyngeal structures. Methods of the invention are useful for the treatment for upper airway conditions such as snoring, obstructive breathing and sleep apnea in a subject.
1 . A method for stiffening the nasopharyngeal area of a subject comprising implanting a filler material comprising an acrylic polymer into one or more nasopharyngeal structures consisting of the group: the soft palate, the anterior palatine arch, and the posterior palatine arch.
2 . The method of claim 1 wherein the filler material is implanted by injection.
3 . The method of claim 2 wherein the injection is performed with a needle with a gauge from about 18 to about 30 gauge.
4 . The method of claim 3 wherein the needle is 28, 29 or 30 gauge.
5 . The method of claim 3 wherein the needle is 26 or 27 gauge.
6 . The method of claim 3 wherein the needle is about 1 inch in length.
7 . The method of claim 3 wherein the needle is curved.
8 . The method of claim 1 wherein the filler material comprises microparticles.
9 . The method of claim 8 wherein the microparticles are about 25 microns to about 200 microns in diameter.
10 . The method of claim 8 wherein the microparticles are about 25 microns to about 100 microns in diameter.
11 . The method of claim 8 wherein the microparticles are about 30 microns to about 50 microns in diameter.
12 . The method of claim 8 wherein the microparticles are round and smooth.
13 . The method of claim 8 wherein the particles are porous or hollow.
14 . The method of claim 1 wherein the acrylic polymer comprises polymethylmethacrylate.
15 . The method of claim 1 wherein the filler material remains at the implantation site for up to about 6 months.
16 . The method of claim 1 wherein the filler material remains at the implantation site for more than 6 months to less than about 3 years.
17 . The method of claim 1 wherein the filler material remains at the implantation site for about 3 years or more.
18 . The method of claim 1 wherein the filler material further comprises collagen.
19 . The method of claim 18 wherein the collagen comprises human collagen.
20 . The method of claim 18 wherein the collagen comprises bovine collagen.
21 . The method of claim 18 wherein the collagen is at least partially denatured or at least partially cross-linked or both.
22 . The method of claim 1 wherein the filler material further comprises a contrast agent.
23 . The method of claim 22 wherein the contrast agent comprises metrizamide, iopamidol, iothalamate sodium, iodomide sodium, or meglumine.
24 . The method of claim 22 wherein the contrast agent comprises Omnipaque®, Visipaque®, or Hypaque-76®.
25 . The method of claim 22 wherein the contrast agent comprises tantalum, tantalum oxide, barium sulfate, gold, tungsten, or platinum.
26 . The method of claim 22 wherein further comprising monitoring the implant by imaging the contrast agent.
27 . The method of claim 1 wherein the filler material is histocompatible.
28 . The method of claim 1 wherein the filler material comprises polymethylmethacrylate microspheres, collagen, a buffer, sodium chloride, and water for injection.
29 . The method of claim 28 wherein the filler material further comprises one or more anesthetics selected from the group consisting of: Articaine, Bupivacaine, Chloroprocaine, Etidocaine, Levobupivacaine, Lidocaine, Mepivacaine, Prilocaine, Procaine, or Tetracaine.
30 . The method of claim 29 wherein the filler material comprises about 20% by weight polymethylmethacrylate microspheres and about 80% by weight of a composition comprising about 3.5% purified bovine collagen, about 2.7% phosphate buffer, about 0.9% sodium chloride, about 0.3% lidocaine hydrochloride, and about 92.6% water for injection.
31 . The method of claim 30 wherein the microparticles are about 25 microns to about 200 microns in diameter.
32 . The method of claim 30 wherein the microparticles are about 25 microns to about 100 microns in diameter.
33 . The method of claim 30 wherein the microparticles are about 30 microns to about 50 microns in diameter.
34 . The method of claim 30 wherein the microparticles are round and smooth.
35 . The method of claim 1 wherein the filler material is implanted in one or more bolus injections.
36 . The method of claim 1 wherein the filler material is implanted by a tunneling technique.
37 . The method of claim 1 wherein the filler material is implanted in a line.
38 . The method of claim 37 wherein the filler material is implanted in a curve that approximates the shape of the biological structure into which it is implanted.
39 . The method of claim 1 wherein the filler material is implanted in two or more lines.
40 . The method of claim 39 wherein at least two lines are parallel to each other.
41 . The method of claim 40 wherein at least two lines intersect each other.
42 . The method of claim 1 wherein the filler material is implanted as a pod.
43 . The method of claim 33 wherein the pod is reshaped after injection.
44 . The method of claim 1 wherein the subject has an upper airway condition.
45 . The method of claim 44 wherein the upper airway defect is flaccidity of one or more of the soft palate, the anterior palatine arch, or the posterior palatine arch.
46 . The method of claim 45 wherein the upper airway defect results in snoring, obstructive breathing or sleep apnea.
47 . A method for stiffening the nasopharyngeal area of a subject comprising implanting a filler material into one or more nasopharyngeal structures consisting of the group: the soft palate, the anterior palatine arch, and the posterior palatine arch. wherein said filler material comprises one or more of the group consisting of: polylactic acid, polypropylene, polytetrafluoroethylene (PTFE), polyhydroxyalkanoate, hyaluronic acid, a protein polymer, polysaccharide-based gel, radiation cross-linked hydrogel, cross-linked water-swellable polymer, a pseudoplastic polymer, a bioelastomer, a three-part injectable polymer or a two-part injectable polymer.
48 . The method of claim 47 wherein the filler material comprises hollow cylinder pellets.
49 . The method of claim 47 wherein the protein polymer comprises keratin, cross-linked blood plasma protein, or a repetitive protein polymer.
50 . A method of treating snoring, sleep apnea or obstructive breathing comprising providing a long-lasting implant comprising polymethylmethacrylate microspheres, collagen, a buffer, sodium chloride, and water for injection and injecting said implant into one or more nasopharyngeal structures consisting of the group: the soft palate, the anterior palatine arch, and the posterior palatine arch.
51 . The method of claim 50 wherein the long-lasting implant further comprises one or more anesthetics selected from the group consisting of: Articaine, Bupivacaine, Chloroprocaine, Etidocaine, Levobupivacaine, Lidocaine, Mepivacaine, Prilocaine, Procaine, or Tetracaine.
52 . The method of claim 51 wherein the long-lasting implant comprises about 20% by weight polymethylmethacrylate microspheres and about 80% by weight of a composition comprising about 3.5% purified bovine collagen, about 2.7% phosphate buffer, about 0.9% sodium chloride, about 0.3% lidocaine hydrochloride, and about 92.6% water for injection.
53 . The method of claim 50 wherein the microparticles are about 25 microns to about 200 microns in diameter.
54 . The method of claim 50 wherein the microparticles are about 25 microns to about 100 microns in diameter.
55 . The method of claim 50 wherein the microparticles are about 30 microns to about 50 microns in diameter.
56 . The method of claim 50 wherein the microparticles are round and smooth.
57 . The method of claim 50 wherein the particles are porous or hollow.
58 . The method of claim 50 wherein the collagen comprises human collagen.
59 . The method of claim 50 wherein the collagen comprises bovine collagen.
60 . The method of claim 50 wherein the collagen is at least partially denatured or at least partially cross-linked or both.
61 . The method of claim 50 wherein the filler material further comprises a contrast agent.
62 . The method of claim 61 wherein the contrast agent comprises metrizamide, iopamidol, iothalamate sodium, iodomide sodium, or meglumine.
63 . The method of claim 61 wherein the contrast agent comprises Omnipaque®, Visipaque®, or Hypaque-76®.
64 . The method of claim 61 wherein the contrast agent comprises tantalum, tantalum oxide, barium sulfate, gold, tungsten, or platinum.
65 . The method of claim 61 wherein further comprising monitoring the implant by imaging the contrast agent.
66 . The method of claim 50 wherein the filler material is histocompatible.