Selectively polymerizable compositions and methods of use in vivo

Abstract

Otologic materials and methods are provided. For example, a cell-adhesive, biodegradable hydrogel scaffold loaded with time-released drugs for repairing chronic tympanic membrane perforations is disclosed, methods of making same and administering same are provided. This hydrogel may promote vascular in-growth and epithelial cell growth of the tympanic membrane with the purpose of closing the perforation and providing a barrier between the external and middle ear. The hydrogel is initially a liquid polymer that only gels upon exposure to specific conditions, such as exposure to light. This scaffold may simultaneously induce repair of the tympanic membrane while preventing or alleviating middle ear infection, thus filling a void in current tympanic membrane perforation therapies.

1 .- 26 . (canceled) 
     
     
         27 . An injectable otologic material, consisting essentially of: a liquid pre-polymer composition comprising at least a first polymer and a solvent, wherein the liquid pre-polymer composition is a mixture of components configured to selectively cure into a polymer matrix under defined conditions in an ear of a patient and has a viscosity prior to administration onto the tympanic membrane and prior to activation into the polymer matrix permitting administration through a syringe while also being sufficiently viscous such that it can be positioned to cover a tympanic membrane perforation without falling through to the middle ear cavity and, which when activated in situ in the ear of a patient results in the liquid pre-polymer composition assembling into the polymer matrix suitable for repairing or aiding the repair of a tympanic membrane perforation, and further wherein the liquid pre-polymer composition has a viscosity of about 2800 cP or greater. 
     
     
         28 . An injectable otologic material according to  claim 27 , wherein the liquid pre-polymer composition comprises an initiator. 
     
     
         29 . An injectable otologic material according to  claim 27 , wherein the liquid pre-polymer composition further comprises a therapeutic composition, and the polymer matrix has a porosity and average pore size sufficient to release the therapeutic composition over a desired time period. 
     
     
         30 . An injectable otologic material according to  claim 27 , wherein repairing or aiding the repair comprises assembling the liquid pre-polymer composition into a polymer matrix stiff enough to function as a scaffold on which epithelial cells of the tympanic membrane can migrate, adhere and grow. 
     
     
         31 . An injectable otologic material according to  claim 27 , wherein the polymer matrix is a hydrogel. 
     
     
         32 . An injectable otologic material according to  claim 30 , wherein the at least first polymer is chosen to result in a functionalized scaffold having a cell-binding domain for improving cell migration and adhesion. 
     
     
         33 . An injectable otologic material according to  claim 31 , wherein the hydrogel is a photo-polymerizable hydrogel and the composition comprises an initiator, which is a photoinitiator. 
     
     
         34 . An injectable otologic material according to  claim 33 , wherein activating comprises exposing the liquid pre-polymer composition to UV light, visible light or blue light in situ as determined by the photoinitiator. 
     
     
         35 . An injectable otologic material according to  claim 33  wherein the photoinitiator is chosen from: Irgacure 2959, eosin Y in conjunction with 1-vinyl-2 pyrrolidinone and triethanolamine, camphorquinone, and riboflavin 5′-monophosphate sodium salt. 
     
     
         36 . An injectable otologic material according to  claim 27 , wherein the at least first polymer is chosen from polyethylene glycols (PEG), polysaccharides, poly(lactic acid)s, polyurethanes, poly(propylene glycols), poly(propylene fumarate-co-ethylene glycols), poly(hydroxyethyl methacrylates), polymethyl methacrylates, polyesters, gelatins, alginates, starches, dextrans, polyvinylpyrrolidones, poly(2-acrylamido-2-methyl-1-propanesulfonic acid), polyvinyl alcohols, polypeptides, polyacrylates, agaroses, celluloses, k-carrageenans, pectins, chondroitin sulfates, proteins and derivatives and analogs thereof. 
     
     
         37 . An injectable otologic material according to  claim 36 , wherein the at least first polymer is chosen from PEGs, polysaccharides, and derivatives and analogs thereof. 
     
     
         38 . An injectable otologic material according to  claim 37 , wherein the polysaccharides are chosen from methacrylated chitosans and methacrylated hyaluronic acids. 
     
     
         39 . An injectable otologic material according to  claim 38 , wherein the methacrylated chitosans are at least about 40% methacrylated, and the methacrylated hyaluronic acids are at least about 30% methacrylated. 
     
     
         40 . An injectable otologic material according to  claim 39 , wherein the methacrylated hyaluronic acids are at least about 90% methacrylated. 
     
     
         41 . An injectable otologic material according to  claim 38 , wherein the at least first polymer is methacrylated chitosan, or the at least first polymer is methacrylated hyaluronic acid, or the at least first polymer is chosen from a first polymer which is a methacrylated chitosan and a second polymer which is chosen from a methacrylated hyaluronic acid and hyaluronic acid, or the at least first polymer is a first polymer which is a PEG, a second polymer and optionally a third polymer, wherein the second and third polymer are chosen from chitosans and hyaluronic acids. 
     
     
         42 . An injectable otologic material according to  claim 36 , wherein the at least first polymer has molecular weight ranging from about 100 to about 1,000,000 g/mol. 
     
     
         43 . injectable otologic material according to  claim 42 , wherein the at least first polymer has a molecular weight ranging from about 1000 to about 4000 g/mol. 
     
     
         44 . A liquid pre-polymer composition adapted for administration on a tympanic membrane, comprising: at least a first polymer and a solvent, wherein the liquid pre-polymer composition is sufficiently viscous such that it can be positioned to cover a tympanic membrane perforation without falling through to the middle ear cavity both prior to administration on the tympanic membrane and prior to activation of curing into the polymer matrix and, which when activated in situ in the ear of a patient results in the liquid pre-polymer composition assembling into a polymer matrix suitable for repairing or aiding the repair of a tympanic membrane perforation, and further wherein the liquid pre-polymer composition has a viscosity of about 2800 cP or greater. 
     
     
         45 . A liquid pre-polymer composition according to  claim 44 , wherein the liquid pre-polymer composition has a viscosity of about 3000 cP or greater. 
     
     
         46 . An injectable otologic material according to  claim 27 , wherein the liquid pre-polymer composition has a viscosity of about 3000 cP or greater.