Malleable implants including an oxysterol and methods of use

Abstract

Provided is a malleable implant configured to fit at or near a bone defect site to promote bone growth, the malleable implant comprising: a biodegradable polymer, mineral particles, and an oxysterol, the implant configured to become moldable upon being wetted with a fluid. Methods of making and use are further provided.

1 - 19 . (canceled) 
     
     
         20 . A method of treating a bone defect site, the method comprising wetting an implant, the implant comprising a biodegradable polymer in an amount of about 0.1 wt % to about 20 wt % of the implant, mineral particles in an amount of about 0.1 wt % to about 95 wt % of the implant, and an active agent comprising an oxysterol, the implant configured to become moldable upon being wetted with the fluid; molding the implant to a desired shape to fit into the bone defect site; and implanting the implant at the bone defect site. 
     
     
         21 . A method according to  claim 20 , wherein the implant is moldable and comprises autograft, allograft and/or xenograft bone particles. 
     
     
         22 . A method according to  claim 20 , wherein the implant is configured to form a coherent mass and be moldable after being wetted with the fluid. 
     
     
         23 . A method according to  claim 20 , further comprising an expandable phase configured to expand upon being wetted with the fluid, the expandable phase being in an amount of about 0.1 wt % to about 5.0 wt % of the implant. 
     
     
         24 . A method according to  claim 23 , wherein the expandable phase is in an amount of about 2.0 wt % to about 4.0 wt % of the implant, the biodegradable polymer is in an amount of about 8.0 wt % to about 13 wt % of the implant, the mineral particles are in an amount of about 50 wt % to about 80 wt % of the implant, and the oxysterol is in an amount of about 5.0 wt % to about 45 wt % of the implant. 
     
     
         25 . A method according to  claim 23 , wherein the expandable phase comprises carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, carbomers, alginic acid, ethyl cellulose, gelatin, magnesium aluminum silicate, methyl cellulose, poloxamers, polyvinyl alcohol, sodium alginate, tragacanth, xanthan gum, glycosaminoglycan, hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratin sulfate, heparin, heparan sulfate, hyaluronan, mannitol, PEG, magnesium alginate, glycerol or combinations thereof. 
     
     
         26 . A method according to  claim 20 , wherein the biodegradable polymer comprises porcine-derived collagen, human-derived collagen, bovine-derived collagen, piscine-derived collagen, ovine-derived collagen, recombinant collagen, gelatin, or combinations thereof. 
     
     
         27 . A method according to  claim 20 , wherein (i) the mineral particles comprise bone powder, demineralized bone powder, porous calcium phosphate ceramics, hydroxyapatite, tricalcium phosphate, bioactive glass or a combination thereof; (ii) the mineral particles include a particle size between about 125 μm and about 750 μm; (iii) the mineral particles comprise tricalcium phosphate and hydroxyapatite in a ratio of about 70:30 to about 90:10; or (iv) the mineral particles comprise tricalcium phosphate and hydroxyapatite in a ratio of about 85:15. 
     
     
         28 . A method according to  claim 20 , wherein the oxysterol comprises (3S,5S,6S,8R,9S,10R,13S,14S,17S) 17-((S)-2-hydroxyoctan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]-phenanthrene-3,6-diol (Oxy133), or hydrates, solvates, amorphous forms, or pharmaceutically acceptable salts thereof. 
     
     
         29 . A method according to  claim 20 , wherein the fluid comprises water, sodium chloride, dextrose, Lactated Ringer's solution, blood, bone marrow or a combination thereof. 
     
     
         30 . A method according to  claim 20 , wherein the implant comprises an oxysterol comprising (3S,5S,6S,8R,9S,10R,13S,14S,17S) 17-((S)-2-hydroxyoctan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]-phenanthrene-3,6-diol (Oxy133) in an amount of about 0.1 wt % to about 60 wt % of the implant. 
     
     
         31 . A method according to  claim 30 , wherein the Oxy133 is in monohydrate form. 
     
     
         32 . A method according to  claim 20 , wherein the implant comprises physiologically acceptable saline and bone graft, the implant having 1.46 cc of physiologically acceptable saline for a 2 cc bone graft. 
     
     
         33 . An implant according to  claim 20 , wherein the implant has an inherent viscosity from about 0.10 dL/g to about 1.2 dL/g. 
     
     
         34 . A method of treating a bone defect site, the method comprising fitting a malleable implant, the malleable implant comprising: a biodegradable polymer in an amount of about 0.1 wt % to about 20 wt % of the implant, mineral particles in an amount of about 0.1 wt % to about 95 wt % of the implant, and an oxysterol, the implant configured to become moldable upon being wetted with a fluid; molding the malleable implant to a desired shape to fit into the bone defect site; and implanting the malleable implant at the bone defect site. 
     
     
         35 . A method according to  claim 34 , wherein the implant is moldable and comprises autograft, allograft and/or xenograft bone particles. 
     
     
         36 . A method according to  claim 34 , wherein the implant is configured to form a coherent mass and be moldable after being wetted with the fluid. 
     
     
         37 . A method according to  claim 34 , further comprising an expandable phase configured to expand upon being wetted with the fluid, the expandable phase being in an amount of about 0.1 wt % to about 5.0 wt % of the implant. 
     
     
         38 . A method according to  claim 34 , wherein the expandable phase is in an amount of about 2.0 wt % to about 4.0 wt % of the implant, the biodegradable polymer is in an amount of about 8.0 wt % to about 13 wt % of the implant, the mineral particles are in an amount of about 50 wt % to about 80 wt % of the implant, and the oxysterol is in an amount of about 5.0 wt % to about 45 wt % of the implant. 
     
     
         39 . A method of treating a bone defect site, the method comprising fitting a malleable implantable matrix, the matrix comprising: a biodegradable polymer in an amount of about 0.1 wt % to about 15 wt % of the matrix, mineral particles in an amount of about 0.1 wt % to about 95 wt % of the matrix, and an active agent comprising an oxysterol, the matrix configured to become moldable upon being wetted with a fluid; molding the matrix to a desired shape to fit into the bone defect site; and implanting the matrix at the bone defect site.