REINFORCED TISSUE SHIELDS
Self-reinforced tissue shields are useful as ophthalmic shields, wound dressings, wound barriers, nerve repair, therapeutic drug delivery devices and the like. The self-reinforced tissue protective shields comprise gelatin, chitosan and reinforce and are made by a method comprising forming inter-molecular locking within a solution through electrostatic forces, eliminating the use of extra cross-linking methods, the solution mainly comprising natural existing polymers that are biodegradable and biocompatible.
1 . A reinforced tissue shield comprising gelatin, chitosan, and a reinforcer, wherein the tissue shield is biocompatible and biodegradable in biological environments.
2 . The tissue shield of claim 1 , wherein the reinforcer maintains a desired shape of the tissue shield.
3 . The tissue shield of claim 2 , wherein the reinforcer is water swellable, has a fibrous structure, and provides mechanical strength.
4 . The tissue shield of claim 1 , wherein the reinforcer is selected from insoluble fibrous polypeptides, polysaccharides, synthetic polymers and combinations thereof.
5 . The tissue shield of claim 4 , wherein the insoluble fibrous polypeptides are selected from the group consisting of keratins, fibrin, neurofilaments, vimentin-like proteins, lamins, collagen and combinations thereof.
6 . The tissue shield of claim 4 , wherein the insoluble fibrous polysaccharides are selected from the group consisting cellulose, alginate, pectin, chitin and combinations thereof.
7 . The tissue shield of claim 4 , wherein the insoluble fibrous synthetic polymers are selected from the group consisting of polylactic acid, polycapralactone, polyurethane, polyacrylates selected from polyHEMA and PMMA and combinations thereof.
8 . The tissue shield of claim 5 , wherein the reinforcer is insoluble collagen fibers present in an amount of from about 3 to about 8% by weight of the total dry weight of the tissue shield.
9 . The tissue shield of claim 5 , wherein the reinforcer is insoluble collagen fibers and is present in an amount of from about 3.5 to about 39% by weight of the total dry weight of the tissue shield.
10 . The tissue shield of claim 1 , wherein the tissue shield is not cross-linked.
11 . The tissue shield of claim 1 , wherein the gelatin and chitosan form inter-molecular complexes through electrostatic interaction.
12 . The tissue shield of claim 1 , wherein the tissue shield has a desired dissolution rate.
13 . The tissue shield of claim 1 , wherein the desired dissolution rate is determined by pre-selecting a ratio of gelatin to chitosan in the tissue shield, wherein an increased ratio of gelatin to chitosan correlates to an increased dissolution rate.
14 . The tissue shield of claim 1 , wherein the gelatin is present in an amount of from about 5 to about 70% by weight of the total dry weight of the tissue shield.
15 . The tissue shield of claim 14 , wherein the gelatin is present in an amount of from about 6 to about 65% by weight of the total dry weight of the tissue shield.
16 . The tissue shield of claim 1 , wherein the chitosan is present in an amount of from about 5 to about 70% by weight of the total dry weight of the tissue shield.
17 . The tissue shield of claim 1 , wherein the chitosan is present in an amount of from about 6 to about 65% by weight of the total dry weight of the tissue shield.
18 . The tissue shield of claim 1 , further comprising one or more of an additive and a pharmaceutical agent.
19 . The tissue shield of claim 16 , wherein the pharmaceutical agent is an antiseptic, an antimicrobial agent, an antibiotic, and anti-inflammatory, an antiproliferative agent, or combinations thereof.
20 . The tissue shield of claim 19 , wherein the antiseptic is silver, iodine, phenols, terpenes, triarylmethane dyes, quaternary ammonium compounds selected from chlorhexidine, polyhexamethylene biguanide, benzalkonium chloride, and combinations thereof.
21 . The tissue shield of claim 20 , wherein the silver is silver nitrate, silver acetate, silver lactate, silver sulfate, silver citrate, silver phosphate, silver oxide, silver colloid, silver nanoparticles or combinations thereof.
22 . The tissue shield of claim 19 , wherein the antibiotic is an aminoglycoside selected from amikacin, gentamicin, kanamycin, tobramycin or a macrolide selected from azithromycin, clarithromycin, erythromycin, or a B-lactam selected from penicillin, piperacillin, cephalexin, cefazolin, cefixime, imipenem, or a quinolone selected from nalidixic acid, ciprofloxacin, moxifloxacin, trovafloxacin, or clindamycin, vancomycin, rifampin, minocycline, and combinations thereof.
23 . The tissue shield of claim 19 , wherein the antiproliferative is selected from sirolimus, everolimus, halofuginone, paclitaxel, and combinations thereof.
24 . The tissue shield of claim 19 , wherein the anti-inflammatory is a corticosteroid selected from hydrocortisone, prednisolone, triamcinolone acetonide, dexamethasone, prednicarbate, or a non-steroidal anti-inflammatory selected from aspirin, ibuprofen, naproxen, and combinations thereof.
25 . The tissue shield of claim 18 , wherein the additive is a material that increases the flexibility and/or reduces the brittleness of the tissue shield.
26 . The tissue shield of claim 25 , wherein the additive is selected from polyethylene glycol (PEG), glycerol, propylene glycol, dibutyl phthalate, triacetin, triethyl citrate, and combinations thereof.
27 . The tissue shield of claim 25 , wherein the additive is present in an amount of from about 5 to about 30% by weight of the total dry weight of the tissue shield.
28 . The tissue shield of claim 27 , wherein the additive is present in an amount of from about 5 to about 15% by weight of the total dry weight of the tissue shield.
29 . The tissue shield of claim 1 , wherein the tissue shield is flat, tubular or curved.
30 . The tissue shield of claim 1 , wherein the tissue shield is hydrated or dehydrated.
31 . The tissue shield of claim 1 , wherein the tissue shield is a wound shield.
32 . The tissue shield of claim 1 , wherein the tissue shield has a thickness of from about 0.02 mm to about 0.35 mm.
33 . The tissue shield of claim 1 , wherein the tissue shield is an ophthalmic shield.
34 . The tissue shield of claim 33 , comprising a single curvature of about 0.02 to about 0.06 mm thickness and a radius of base curvature of about 9.0 to about 12.25 mm and a diameter of about 14 mm to about 20 mm.
35 . The tissue shield of claim 33 , wherein said shield is configured as a curved disc or a ring having an aperature therein.
36 . A method of covering and/or protecting a wound, the method comprising applying the tissue shield of claim 1 to the wound.
37 . The method of claim 36 , wherein the tissue shield inhibits microbial contamination of the wound.
38 . A method of producing a reinforced tissue shield, the method comprising:
mixing gelatin, chitosan, and a reinforcer together to produce a matrix; and
dehydrating the matrix to produce the tissue shield.
39 . The method of claim 38 , wherein the tissue shield is formed into a desired shape without the use of chemical or physical cross-linking procedures.
40 . The method of claim 38 , further comprising molding the matrix into a desired shape prior to dehydrating the matrix.
41 . The method of claim 38 , wherein the gelatin, chitosan, and reinforcer are produced as separate solutions that are then mixed together in a desired ratio to produce the matrix.
42 . The method of claim 38 , further comprising centrifuging the matrix to remove bubbles formed after mixing.
43 . The method of claim 42 , wherein the matrix is centrifuged for about 2 to about 30 minutes at a temperature of about 20° C. to about 30° C. at from about 1000 to about 3000 rpm.
44 . The method of claim 38 further comprising dehydrating the matrix at about 20° C. to about 30° C. and from about 45 to about 80% relative humidity for about 48 hours.
45 . The method of claim 44 , further comprising placing the tissue shield in a vacuum oven for complete dehydration for about 4 to about 12 hours at a temperature of from about 23° C. to about 30° C. under a pressure from about 20 to about 30 mmHg.
46 . The method of claim 38 , wherein the dehydrated tissue shield is rehydrated prior to use.
47 . The method of claim 46 , wherein the dehydrated tissue shield is rehydrated in a solution comprising a therapeutically active agent.
48 . The method of claim 46 , wherein the dehydrated tissue shield is rehydrated in a balanced physiological saline solution.