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ULTRASHORT TETRAMERIC PEPTIDE NANOGELS SUPPORT TISSUE GRAFT FORMATION, WOUND HEALING AND 3D BIOPRINTING

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  • Publication Date:
    December 21, 2023
  • معلومة اضافية
    • Document Number:
      20230405177
    • Appl. No:
      18/218192
    • Application Filed:
      July 05, 2023
    • نبذة مختصرة :
      Newly developed peptide nanogels provide native cues to human dermal fibroblasts as well as mouse myoblast cells and promote proliferation and extensive network formation in vitro is presented. The results represent an improvement in the fabrication of dermal grafts as well as 3D skin models. In addition, the application of these ultrashort peptide nanogels on full-thickness wounds in a minipig model demonstrated biocompatibility with the minipig skin tissue, as the peptide nanogels did not trigger wound inflammation. Thus, they can be considered as a safe biomaterial for topical applications. It is shown that both peptides are printable. The ability to print peptides and the return of high cell viability within the printed construct will open up the possibility of 3D bioprinting of different cell types in future.
    • Claim:
      1. An ultrashort self-assembling amphiphilic peptide wherein said aliphatic amino acids and said aromatic amino acids and said polar amino acids are either D amino acids or L amino acids, comprising: at least one peptide selected from a group of peptides having a general formula selected from AnBmX, BmAnX, XAnBm, and XBmAn, wherein the total number of amino acids of the ultrashort self-assembling amphiphilic peptide wherein said aliphatic amino acids and said aromatic amino acids and said polar amino acids are either D amino acids or L amino acids, does not exceed 7 amino acids; wherein A is an aliphatic amino acids, selected from the group consisting of: isoleucine, leucine, norleucine, cyclohexylalanine, valine, alanine, glycin, homoallylglycine and homopropargylglycine or any combination thereof, with n being an integer being selected from 0-5; wherein B is comprised of at least one aromatic amino acid selected from the group consisting of: tyrosine, tryptophan, phenylalanine, L-DOPA, or comprised of a peptidomimetic amino acid that is the aliphatic counterpart of the aromatic amino acid, which is the counterpart of amino acid phenylalanine with m being an integer being selected from 0-3; and wherein X is comprised of a polar amino acid, selected from the group consisting of: aspartic acid, glutamic acid, lysine, arginine, histidine, cysteine, serine, threonine, asparagine, and glutamine, 5-N-ethyl glutamine (theanine), citrulline, thio citrulline, homocysteine, methionine, ethionine, selenomethionine, telluromethionine, allo threonine, homoserine, homoarginine, ornithine, N(6) carboxymethyllysine, or any combination thereof, where the polar group is selected from a hydroxyl, an ether, a carboxyl, an imido, an amido, an amino, an ester, a guanidino, a thio, a thioether, a seleno, and a telluro group.
    • Claim:
      2. The ultrashort self-assembling amphiphilic peptide of claim 1, wherein the peptide is a tetrameric amphiphilic self-assembling peptide.
    • Claim:
      3. The ultrashort self-assembling amphiphilic peptide of claim 1, wherein the peptide has amphiphilic peptide sequences with a hydrophobic tail and a hydrophilic head group.
    • Claim:
      4. The ultrashort self-assembling amphiphilic peptide of claim 1, wherein the peptide self-assembles into nanofibers that form three-dimensional nanogel.
    • Claim:
      5. The ultrashort self-assembling amphiphilic peptide of claim 1, wherein the peptide generates macromolecular nanofibrous hydrogel in an aqueous solution.
    • Claim:
      6. The ultrashort self-assembling peptide of claim 1, wherein the peptide is at least one selected from the group consisting of IVFK, and IVZK.
    • Claim:
      7. (canceled)
    • Claim:
      8. (canceled)
    • Claim:
      9. (canceled)
    • Claim:
      10. (canceled)
    • Claim:
      11. The ultrashort self-assembling amphiphilic peptide of claim 1, wherein the peptide having helical nano-fibers organize themselves into supramolecular 3D-meshed nanofibrous networks with an average fiber diameter of around 5-30 nm.
    • Claim:
      12. (canceled)
    • Claim:
      13. (canceled)
    • Claim:
      14. A method of wound treatment comprising: applying a material to a subject, wherein the material comprises an ultrashort self-assembling amphiphilic peptide wherein said aliphatic amino acids and said aromatic amino acids and said polar amino acids are either D amino acids or L amino acids, comprising: at least one peptide selected from a group of peptides having a general formula selected from AnBmX, BmAnX, XAnBm, and XBmAn, wherein the total number of amino acids of the ultrashort self-assembling amphiphilic peptide wherein said aliphatic amino acids and said aromatic amino acids and said polar amino acids are either D amino acids or L amino acids, does not exceed 7 amino acids; wherein A is an aliphatic amino acids, selected from the group consisting of: isoleucine, leucine, norleucine, cyclohexylalanine, valine, alanine, glycin, homoallylglycine and homopropargylglycine or any combination thereof, with n being an integer being selected from 0-5; wherein B is comprised of at least one aromatic amino acid selected from the group consisting of: tyrosine, tryptophan, phenylalanine, L-DOPA, or comprised of a peptidomimetic amino acid that is the aliphatic counterpart of the aromatic amino acid, which is the counterpart of amino acid phenylalanine with m being an integer being selected from 0-3; and wherein X is comprised of a polar amino acid, selected from the group consisting of: aspartic acid, glutamic acid, lysine, arginine, histidine, cysteine, serine, threonine, asparagine, and glutamine, 5-N-ethyl glutamine (theanine), citrulline, thio citrulline, homocysteine, methionine, ethionine, selenomethionine, telluromethionine, allo threonine, homoserine, homoarginine, ornithine, N(6) carboxymethyllysine, or any combination thereof, where the polar group is selected from a hydroxyl, an ether, a carboxyl, an imido, an amido, an amino, an ester, a guanidino, a thio, a thioether, a seleno, and a telluro group.
    • Claim:
      15. The method of claim 14, wherein the subject is a human.
    • Claim:
      16. The method of claim 14, wherein the subject is selected from the group consisting of a mammal, a reptile, a bird, a fish, an amphibian, and an invertebrate.
    • Claim:
      17. A hydrogel or organogel comprising the peptide of claim 1.
    • Claim:
      18. (canceled)
    • Claim:
      19. (canceled)
    • Claim:
      20. (canceled)
    • Claim:
      21. (canceled)
    • Claim:
      22. (canceled)
    • Claim:
      23. (canceled)
    • Claim:
      24. (canceled)
    • Claim:
      25. (canceled)
    • Claim:
      26. (canceled)
    • Claim:
      27. (canceled)
    • Claim:
      28. (canceled)
    • Claim:
      29. (canceled)
    • Claim:
      30. (canceled)
    • Claim:
      31. A method of preparing a hydrogel or organogel comprising dissolving a peptide in an aqueous solution or an organic solution, respectively, wherein the peptide comprises: at least one peptide selected from a group of peptides having a formula selected from AnBmX, BmAnX, XAnBm, and XBmAn, wherein the total number of amino acids of the ultrashort self-assembling does amphiphilic peptide wherein said aliphatic amino acids and said aromatic amino acids and said polar amino acids are either D amino acids or L amino acids, not exceed 7 amino acids; wherein A is an aliphatic amino acids, selected from the group consisting of: isoleucine, leucine, norleucine, cyclohexylalanine, valine, alanine, glycin, homoallylglycine and homopropargylglycine or any combination thereof, with n being an integer being selected from 0-5; wherein B is comprised of at least one aromatic amino acid selected from the group consisting of: tyrosine, tryptophan, phenylalanine, L-DOPA, or comprised of a peptidomimetic amino acid that is the aliphatic counterpart of the aromatic amino acid, which is the counterpart of amino acid phenylalanine with m being an integer being selected from 0-3; and wherein X is comprised of a polar amino acid, selected from the group consisting of: aspartic acid, glutamic acid, lysine, arginine, histidine, cysteine, serine, threonine, asparagine, and glutamine, 5-N-ethyl glutamine (theanine), citrulline, thio citrulline, homocysteine, methionine, ethionine, selenomethionine, telluromethionine, allo threonine, homoserine, homoarginine, ornithine, N(6) carboxymethyllysine, or any combination thereof, where the polar group is selected from a hydroxyl, an ether, a carboxyl, an imido, an amido, an amino, an ester, a guanidino, a thio, a thioether, a seleno, and a telluro group.
    • Claim:
      32. The method of claim 31, wherein the peptide is a tetrameric amphiphilic self-assembling peptide.
    • Claim:
      33. The method of claim 31, wherein the peptide has amphiphilic peptide sequences with a hydrophobic tail and a hydrophilic head group.
    • Claim:
      34. (canceled)
    • Claim:
      35. (canceled)
    • Claim:
      36. The method of claim 31, wherein the peptide is at least one selected from the group consisting of IVFK, and IVZK.
    • Claim:
      37. (canceled)
    • Claim:
      38. (canceled)
    • Claim:
      39. (canceled)
    • Claim:
      40. (canceled)
    • Claim:
      41. (canceled)
    • Claim:
      42. (canceled)
    • Claim:
      43. A kit of parts, wherein the kit comprises a first container with the peptide of claim 1 and a second container with an aqueous or organic solution.
    • Claim:
      44. (canceled)
    • Claim:
      45. (canceled)
    • Claim:
      46. (canceled)
    • Claim:
      47. (canceled)
    • Claim:
      48. (canceled)
    • Claim:
      49. (canceled)
    • Claim:
      50. (canceled)
    • Claim:
      51. (canceled)
    • Claim:
      52. (canceled)
    • Claim:
      53. (canceled)
    • Claim:
      54. (canceled)
    • Claim:
      55. A kit comprising an effective amount of a material, wherein the material comprises the peptide of claim 1 and wherein the material is applied in at least one selected from the group consisting of 2D-3D printing and 2D-3D molding.
    • Claim:
      56. A wound dressing or wound healing agent comprising a hydrogel or organogel comprising the peptide of claim 1.
    • Claim:
      57. (canceled)
    • Claim:
      58. (canceled)
    • Claim:
      59. (canceled)
    • Claim:
      60. (canceled)
    • Claim:
      61. (canceled)
    • Claim:
      62. (canceled)
    • Claim:
      63. (canceled)
    • Claim:
      64. (canceled)
    • Claim:
      65. (canceled)
    • Claim:
      66. (canceled)
    • Claim:
      67. (canceled)
    • Claim:
      68. A pharmaceutical composition comprising the peptide of claim 1.
    • Claim:
      69. (canceled)
    • Claim:
      70. (canceled)
    • Claim:
      71. (canceled)
    • Claim:
      72. (canceled)
    • Claim:
      73. (canceled)
    • Claim:
      74. (canceled)
    • Claim:
      75. (canceled)
    • Claim:
      76. (canceled)
    • Claim:
      77. (canceled)
    • Claim:
      78. (canceled)
    • Claim:
      79. (canceled)
    • Claim:
      80. A method of wound treatment comprising: administering a hydrogel or organogel comprising the peptide of claim 1 to a subject via a device.
    • Claim:
      81. (canceled)
    • Claim:
      82. (canceled)
    • Claim:
      83. (canceled)
    • Claim:
      84. (canceled)
    • Claim:
      85. (canceled)
    • Claim:
      86. (canceled)
    • Claim:
      87. (canceled)
    • Claim:
      88. (canceled)
    • Claim:
      89. (canceled)
    • Claim:
      90. (canceled)
    • Claim:
      91. (canceled)
    • Claim:
      92. (canceled)
    • Claim:
      93. (canceled)
    • Claim:
      94. (canceled)
    • Current International Class:
      61; 07
    • الرقم المعرف:
      edspap.20230405177