초록 ▼

The subject invention concerns a composite comprising an organic fluid-swellable, fibrous matrix, such as collagen, and a mineral phase, such as calcium carbonate or phosphate mineral phase, for use as a biomimetic of bone. In another aspect, the subject invention concerns a process for making a com

The subject invention concerns a composite comprising an organic fluid-swellable, fibrous matrix, such as collagen, and a mineral phase, such as calcium carbonate or phosphate mineral phase, for use as a biomimetic of bone. In another aspect, the subject invention concerns a process for making a composite involving the inclusion of acidic polymers to a supersaturated mineralizing solution, in order to induce an amorphous liquid-phase precursor to the inorganic mineral, which is then absorbed (pulled by capillary action) into the organic matrix. Advantageously, once solidified, a high mineral content can be achieved, with the inorganic mineral crystals embedded within the collagen fibers (intrafibrillarly) and oriented such that they are aligned along the long axes of the fibers of the organic matrix, thereby closely mimicking the natural structure of bone. The present invention further concerns a method of treating a patient suffering from a bone defect by applying a biomimetic composite to the bone defect site.

대표청구항 ▼

We claim: 1. A process for making organic/inorganic composites, said method comprising: contacting a polymer with a mineralizing solution under conditions suitable to form an amorphous inorganic liquid-phase mineral precursor, wherein said polymer is one that becomes negatively charged when placed

We claim: 1. A process for making organic/inorganic composites, said method comprising: contacting a polymer with a mineralizing solution under conditions suitable to form an amorphous inorganic liquid-phase mineral precursor, wherein said polymer is one that becomes negatively charged when placed in an aqueous solution; and contacting said amorphous inorganic liquid-phase mineral precursor with a fluid-swellable, fibrous, organic matrix, wherein said amorphous inorganic liquid-phase mineral precursor is absorbed into, and subsequently hardens and crystallizes within, said fluid-swellable, fibrous, organic matrix. 2. The process according to claim 1, wherein said polymer has a molecular weight in the range of about 1000 to about 100,000 g/mol. 3. The process according to claim 1, wherein contacting said amorphous inorganic liquid-phase mineral precursor with said fluid-swellable, fibrous, organic matrix is repeated until said fluid-swellable, fibrous, organic matrix is sufficiently mineralized. 4. The process according to claim 1, wherein said polymer comprises at least one member selected from the group consisting of polyacrylic acid, polymethacrylic acid, sulfonated polymers, phosphorylated proteins or peptides, phosphorylated polymers, sulfated polysaccharides, sulfated glycoproteins, polyaspartic acid, polyglutamic acid, polyaspartate, polyvinyl phosphate, and polyvinyl phosphonate, or combinations thereof. 5. The process according to claim 1, wherein said fluid-swellable, fibrous, organic matrix comprises a material selected from at least one member of the group consisting of collagen, elastin, chitin, chitosan, cellulose, and peptide nanofibers. 6. The process according to claim 1, wherein said fluid-swellable, fibrous, organic matrix comprises collagen fibers. 7. The process according to claim 6, wherein collagen of said collagen fibers is selected from the group consisting of collagen type I, collagen type II, collagen type III, collagen type IV, collagen type V, collagen type VI, collagen type VII, collagen type VIII, collagen type IX, collagen type X, collagen type XI, collagen type XII, collagen type XIII, collagen type XIV, collagen type XV, collagen type XVI, collagen type XVII, collagen type XVIII, collagen type XIX, and collagen type XX, or combinations thereof. 8. The process according to claim 1, wherein said amorphous inorganic liquid-phase mineral precursor comprises at least one member selected from the group consisting of calcium phosphate, calcium carbonate, hydroxyapatite, strontium carbonate, calcium sulfate, calcium oxalate, magnesium-bearing calcium carbonate, and magnesium-bearing calcium phosphate. 9. The process according to claim 1, wherein said amorphous inorganic liquid-phase mineral precursor comprises at least one member selected from the group consisting of hydroxyapatite, octacalcium phosphate, tricalcium phosphate, carbonated hydroxyapatite, fluorinated hydroxyapatite, brushite, magnesium containing hydroxyapatite, dicalcium phosphate dihydrate, and amorphous calcium phosphate. 10. The process according to claim 1, wherein said method further comprises associating a biologically active agent within said composite before contacting said amorphous inorganic liquid-phase mineral precursor with said fluid-swellable, fibrous, organic matrix. 11. The process according to claim 10, wherein said biologically active agents comprise at least one member selected from the group consisting of medicaments; vitamins; mineral supplements; substances used for the treatment, diagnosis, or mitigation of disease or illness; substances affecting the structure or function of the body; drugs; antimicrobial agents; antifungal agents; antibacterial agents; antiviral agents; antiparasitic agents; growth factors; angiogenic factors; anaesthetics; mucopolysaccharides; metals; cells; acid mucopolysaccharides; proteins; enzymes, peptides; and wound healing agents. 12. The process according to claim 1, wherein said amorphous inorganic liquid-phase mineral precursor is formed by combining calcium salt and said polymer to form an aqueous solution, and reacting said aqueous solution with ammonium carbonate vapor or ammonium phosphate vapor. 13. The process according to claim 12, wherein the aqueous solution is reacted with the ammonium carbonate vapor, and wherein the ammonium carbonate vapor is provided through the decomposition of at least one ammonium carbonate material selected from the group consisting of ammonium carbonate monohydrate, ammonium carbonate dihydrate, and ammonium carbamate. 14. The process according to claim 12, wherein the aqueous solution is reacted with the ammonium phosphate vapor, and wherein the ammonium phosphate vapor is provided through the decomposition of at least one ammonium phosphate material selected from the group consisting of ammonium phosphate monobasic, ammonium phosphate dibasic. 15. The process according to claim 1, wherein said amorphous inorganic liquid-phase mineral precursor is formed by combining calcium chloride and a combination of polymers to form an aqueous solution, and reacting said aqueous solution with ammonium phosphate vapor. 16. The process according to claim 1, wherein said amorphous inorganic liquid-phase mineral precursor is formed by combining calcium chloride and a combination of polymers to form an aqueous solution, and reacting said aqueous solution with a phosphate containing solution. 17. The process according to claim 1, wherein said amorphous inorganic liquid-phase mineral precursor is formed by combining calcium salt and a combination of polymers to form an aqueous solution, and reacting said aqueous solution with phosphate generated by enzymatic degradation of phosphate containing compounds. 18. The process according to claim 1, wherein said amorphous inorganic liquid-phase mineral precursor is formed by combining calcium salt and ammonium phosphate, and a combination of polymers to form an aqueous solution, in which precipitation is caused by a change of temperature, change of pH, evaporation, or removal of crystallization inhibitor. 19. The process according to claim 1, wherein said fluid-swellable, fibrous, organic matrix comprises an exterior surface and an interior containing an interstitial space, wherein said amorphous inorganic liquid-phase mineral precursor is absorbed into said interstitial space of said fluid-swellable, fibrous, organic matrix, and deposited onto said exterior surface of said fluid-swellable, fibrous, organic matrix; and wherein said amorphous inorganic liquid-phase mineral precursor deposited onto said exterior surface of said fluid-swellable, fibrous, organic matrix comprises crystals that are non-faceted when solidified. 20. An organic/inorganic composite made according to the process of claim 1. 21. The organic/inorganic composite of claim 20, wherein said fluid-swellable, fibrous, organic matrix comprises a material selected from the group consisting of collagen, elastin, chitin, chitosan, cellulose, and peptide nanofibers. 22. The organic/inorganic composite of claim 20, wherein said amorphous inorganic liquid-phase mineral precursor comprises at least one member selected from the calcium phosphate group consisting of hydroxyapatite, octacalcium phosphate, tricalcium phosphate, carbonated hydroxyapatite, fluorinated hydroxyapatite, brushite, magnesium containing hydroxyapatite, dicalcium phosphate dihydrate, and amorphous calcium phosphate.