Tricalcium Phosphate Binding Peptides And Uses Thereof

Abstract

The invention is directed to a composition comprising all or a portion of a beta-tricalcium phosphate (β-TCP) bound to all or a portion of a β-TCP binding peptide and methods of use thereof.

1 . A beta-tricalcium phosphate (β-TCP) binding peptide comprising the amino acid sequence: LLADTTHHRPWT (SEQ ID NO: 1), GQVLPTTTPSSP (SEQ ID NO: 2), VPQHPYPVPSHK (SEQ ID NO: 3), HNMAPATLHPLP (SEQ ID NO: 4), QSFASLTNPRVL (SEQ ID NO: 5), HTTPTTTYAAPP (SEQ ID NO: 6), QYGVVSHLTHTP (SEQ ID NO: 7), TMSNPITSLISV (SEQ ID NO: 8), IGRISTHAPLHP (SEQ ID NO: 9), MNDPSPWLRSPR (SEQ ID NO: 10), QSLGSMFQEGHR (SEQ ID NO: 11), KPLFTRYGDVAI (SEQ ID NO: 12), MPFGARILSLPN (SEQ ID NO: 13), QLQLSNSMSSLS (SEQ ID NO: 14), TMNMPAKIFAAM (SEQ ID NO: 15), EPTKEYTTSYHR (SEQ ID NO: 16), DLNELYLRSLRA (SEQ ID NO: 17), DYDSTHGAVFRL (SEQ ID NO: 18), SKHERYPQSPEM (SEQ ID NO: 19), HTHSSDGSLLGN (SEQ ID NO: 20), NYDSMSEPRSHG (SEQ ID NO: 21), ANPIISVQTAMD (SEQ ID NO: 22) or a combination thereof. 
     
     
         2 . The composition of  claim 1  wherein the β-TCP binding peptide is fused to one or more additional peptides or proteins. 
     
     
         3 . The composition of  claim 1  wherein the β-TCP binding peptide is fused to each additional peptide or protein via a linker. 
     
     
         4 . The composition of  claim 2  wherein the β-TCP binding peptide is fused to all or a portion of a growth factor or a cytokine. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . A method of delivering epidermal growth factor (EGF) to an individual in need thereof, comprising administering to the individual an effective amount of a composition comprising a beta-tricalcium phosphate (β-TCP) bound to a β-TCP binding peptides, wherein the β-TCP binding peptide is fused to an epidermal growth factor (EGF). 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . A method of repairing bone in an individual in need thereof, comprising administering to the individual an effective amount of a composition comprising a beta-tricalcium phosphate (β-TCP) scaffold bound to one or more β-TCP binding peptides, wherein the one or more β-TCP binding peptides are fused to a growth factor or cytokine. 
     
     
         16 . The method of  claim 15  further comprising administering mesenchymal stem cells (MSCs) to the individual. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 15  wherein the β-TCP binding peptide comprises the amino acid sequence: LLADTTHHRPWT (SEQ ID NO: 1), GQVLPTTTPSSP (SEQ ID NO: 2), VPQHPYPVPSHK (SEQ ID NO: 3), HNMAPATLHPLP (SEQ ID NO: 4), QSFASLTNPRVL (SEQ ID NO: 5), HTTPTTTYAAPP (SEQ ID NO: 6), QYGVVSHLTHTP (SEQ ID NO: 7), TMSNPITSLISV (SEQ ID NO: 8), IGRISTHAPLHP (SEQ ID NO: 9), MNDPSPWLRSPR (SEQ ID NO: 10), QSLGSMFQEGHR (SEQ ID NO: 11), KPLFTRYGDVAI (SEQ ID NO: 12), MPFGARILSLPN (SEQ ID NO: 13), QLQLSNSMSSLS (SEQ ID NO: 14), TMNMPAKIFAAM (SEQ ID NO: 15), EPTKEYTTSYHR (SEQ ID NO: 16), DLNELYLRSLRA (SEQ ID NO: 17), DYDSTHGAVFRL (SEQ ID NO: 18), SKHERYPQSPEM (SEQ ID NO: 19), HTHSSDGSLLGN (SEQ ID NO: 20), NYDSMSEPRSHG (SEQ ID NO: 21), ANPIISVQTAMD (SEQ ID NO: 22) or a combination thereof. 
     
     
         20 . A method of increasing mesenchymal stem cell (MSC) proliferation in an individual in need thereof, comprising administering to the individual MSCs and an effective amount of a composition comprising a beta-tricalcium phosphate scaffold (β-TCP) bound to one or more β-TCP binding peptides, wherein the one or more β-TCP binding peptides are fused to EGF. 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . A method of culturing mesenchymal stem cells (MSCs), comprising
 a) contacting the MSCs with a composition comprising a beta-tricalcium phosphate (β-TCP) scaffold bound to one or more β-TCP binding peptides, wherein the one or more β-TCP binding peptides are fused to EGF, thereby producing a cell culture; and   b) maintaining the cell culture under conditions in which the MSCs proliferate,   
       thereby culturing the MSCs. 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 15  wherein the β-TCP scaffold further comprises polylactide-co-glycolide. 
     
     
         33 . The method of  claim 2  wherein the β-TCP scaffold further comprises one or more porogens. 
     
     
         34 . The method of  claim 33  wherein the porogen is sucrose. 
     
     
         35 . The method of  claim 15  wherein the composition is a concatenated multimer comprising two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty repeats of a β-TCP binding peptide bound to the β-TCP. 
     
     
         36 . The method of  claim 15  wherein each β-TCP binding peptide is fused to the growth factor or cytokine via a linker. 
     
     
         37 . The method of  claim 15  wherein one or more of the β-TCP binding peptides is fused to all or a portion of the growth factor or cytokine. 
     
     
         38 . The method of  claim 15  wherein the growth factor or cytokine is an epidermal growth factor (EGF), a platelet-derived growth factor (PDGF), a bone morphogenic protein 2 (BMP-2), BMP-4, BMP-7, osteogenic protein (OP-1), collagen binding protein or a combination thereof.