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US 12,741,056 B2Granted
Synthetic hydrogel carriers for muscle repair
AssigneeGeorgia Tech Research Corporation
InventorsWoojin Han, Andres J. Garcia, Young C. Jang
Life of this patent
Estimating the term…
Abstract
Disclosed herein are synthetic hydrogels suitable for delivering pro-myogenic agents to injured muscle tissues.
Claims12
A kit comprising:
- a substrate comprising at least one microneedle, and
- a composition comprising at least one pro-myogenic agent, dispersed in a hydrogel matrix,
- wherein the hydrogel matrix comprises a crosslinked hydrophilic polymer network covalently bonded to a plurality of adhesion peptides,
- wherein the crosslinked hydrophilic polymer network has the general formula:
- wherein C represents a core, n is an integer from 20-2,000, Q is a linking moiety, Z is an adhesion peptide, X is a crosslinker, a is greater than 0 and b is greater than 1, provided the sum of a+b does not exceed 7,
- wherein the adhesion peptide comprises the sequence GRGDSPC (SEQ ID NO:
- 1), CRGDS (SEQ ID NO:
- 2), CRGDSP (SEQ ID NO:
- 3), CPHSRN (SEQ ID NO:
- 4), CGWGGRGDSP (SEQ ID NO:
- 5), CGGSIDQVEPYSSTAQ (SEQ ID NO:
- 6), CGGRNIAEIIKDI (SEQ ID NO:
- 7), CGGDITYVRLKF (SEQ ID NO:
- 8), CGGDITVTLNRL (SEQ ID NO:
- 9), CGGRYVVLPR (SEQ ID NO:
- 10), CGGKAFDITYVRLKF (SEQ ID NO:
- 11), CGGEGYGEGYIGSR (SEQ ID NO:
- 12), CGGATLQLQEGRLHFXFDLGKGR, wherein X=Nle (SEQ ID NO:
- 13), CGGSYWYRIEASRTG (SEQ ID NO:
- 14), CGGGEFYFDLRLKGDKY (SEQ ID NO:
- 15), CKGGNGEPRGDTYRAY (SEQ ID NO:
- 16), CKGGPQVTRGDVFTMP (SEQ ID NO:
- 17), CGGNRWHSIYITRFG (SEQ ID NO:
- 18), CGGASIKVAVSADR (SEQ ID NO:
- 19), CGGTTVKYIFR (SEQ ID NO:
- 20), CGGSIKIRGTYS (SEQ ID NO:
- 21), CGGSINNNR (SEQ ID NO:
- 22), CGGSDPGYIGSR (SEQ ID NO:
- 23), CYIGSR (SEQ ID NO:
- 24), CGGTPGPQGIAGQGVV (SEQ ID NO:
- 25), CGGTPGPQGIAGQRVV (SEQ ID NO:
- 26), CGGMNYYSNS (SEQ ID NO:
- 27), CGGKKQRFRHRNRKG (SEQ ID NO:
- 28), CRGDGGGGGGGGGGGGGPHSRN (SEQ ID NO:
- 29), CPHSRNSGSGSGSGSGRGD (SEQ ID NO:
- 30), Acetylated-GCYGRGDSPG (SEQ ID NO:
- 31), ((GPP) 5GPC) (SEQ ID NO:
- 32), CRDGS (SEQ ID NO:
- 33), cyclic RGD {Fd}C (SEQ ID NO:
- 34), CGGRKRLQVQLSIRT (SEQ ID NO:
- 35), CIKVAV (SEQ ID NO:
- 36), CGGAASIKVAVSADR (SEQ ID NO:
- 37), CGGKRTGQYKL (SEQ ID NO:
- 38), CGGTYRSRKY (SEQ ID NO:
- 39), CGGYGGGP (GPP) 5GFOGERPP (GPP) 4GPC (SEQ ID NO:
- 40), CGGKRTGQYKLGSKTGPGQK (SEQ ID NO:
- 41), QAKHKQRKRLKSSC (SEQ ID NO:
- 42), SPKHHSQRARKKKNKNC (SEQ ID NO:
- 43), CGGXBBXBX, wherein B=basic residue and X=hydropathic residue (SEQ ID NO:
- 44), and CGGXBBBXXBX, wherein B=basic residue and X=hydropathic residue (SEQ ID NO:
- 45), or a combination thereof;
- wherein the crosslinker comprises a peptide having the sequence GCRDGPQG↓WGQDRCG (SEQ ID NO:
- 46), GCRDGPQG↓IAGQDRCG (SEQ ID NO:
- 47), GCRDVPMS↓MRGGDRCG (SEQ ID NO:
- 48), GCRDIPVS↓LRSGDRCG (SEQ ID NO:
- 49), GCRDRPFS↓MIMGDRCG (SEQ ID NO:
- 50), GCRDVPLS↓LTMGDRCG (SEQ ID NO:
- 51), GCRDVPLS↓LYSGDRCG (SEQ ID NO:
- 52), GCRDIPES↓LRAGDRCG (SEQ ID NO:
- 53), GCRDSGESPAY↓YTADRCG (SEQ ID NO:
- 54), GCRDGGYAE↓LRMGGDRCG (SEQ ID NO:
- 55), GCRDGGPLG↓LYAGGDRCG (SEQ ID NO:
- 56), or GCRDGPLG↓WARDRCG SEQ ID NO:
- 57), 1,4-dithiothreitol poly (ethylene glycol) dithiol, or a combination thereof;
- wherein the pro-myogenic agent comprises muscle stem cells, muscle satellite cells, a pro-myogenic protein, or a combination thereof;
- and
- wherein C represents a group having the formula:
- wherein q is from 1-6.
65 more elements
A kit comprising:
- a) a syringe comprising a hydrogel precursor;
- b) a mixing vessel comprising a crosslinking agent;
- and
- c) an injection needle;
- wherein either of the syringe or mixing vessel comprise at least one pro-myogenic agent;
- and
- wherein the syringe is in fluid communication with the mixing vessel and injection needle, in which the mixing vessel is disposed between the needle and syringe;
- wherein the hydrogel precursor has the general formula:
- C represents a core, Q represents a linker, Z represents an adhesion peptide, Q1 represents a functional group capable of reacting with cysteine, and the sum of a1+b1 together is an integer of 3 or greater
- wherein the adhesion peptide comprises the sequence GRGDSPC (SEQ ID NO:
- 1), CRGDS (SEQ ID NO:
- 2), CRGDSP (SEQ ID NO:
- 3), CPHSRN (SEQ ID NO:
- 4), CGWGGRGDSP (SEQ ID NO:
- 5), CGGSIDQVEPYSSTAQ (SEQ ID NO:
- 6), CGGRNIAEIIKDI (SEQ ID NO:
- 7), CGGDITYVRLKF (SEQ ID NO:
- 8), CGGDITVTLNRL (SEQ ID NO:
- 9), CGGRYVVLPR (SEQ ID NO:
- 10), CGGKAFDITYVRLKF (SEQ ID NO:
- 11), CGGEGYGEGYIGSR (SEQ ID NO:
- 12), CGGATLQLQEGRLHFXFDLGKGR, wherein X=Nle (SEQ ID NO:
- 13), CGGSYWYRIEASRTG (SEQ ID NO:
- 14), CGGGEFYFDLRLKGDKY (SEQ ID NO:
- 15), CKGGNGEPRGDTYRAY (SEQ ID NO:
- 16), CKGGPQVTRGDVFTMP (SEQ ID NO:
- 17), CGGNRWHSIYITRFG (SEQ ID NO:
- 18), CGGASIKVAVSADR (SEQ ID NO:
- 19), CGGTTVKYIFR (SEQ ID NO:
- 20), CGGSIKIRGTYS (SEQ ID NO:
- 21), CGGSINNNR (SEQ ID NO:
- 22), CGGSDPGYIGSR (SEQ ID NO:
- 23), CYIGSR (SEQ ID NO:
- 24), CGGTPGPQGIAGQGVV (SEQ ID NO:
- 25), CGGTPGPQGIAGQRVV (SEQ ID NO:
- 26), CGGMNYYSNS (SEQ ID NO:
- 27), CGGKKQRFRHRNRKG (SEQ ID NO:
- 28), CRGDGGGGGGGGGGGGGPHSRN (SEQ ID NO:
- 29), CPHSRNSGSGSGSGSGRGD (SEQ ID NO:
- 30), Acetylated-GCYGRGDSPG (SEQ ID NO:
- 31), ((GPP) 5GPC) (SEQ ID NO:
- 32), CRDGS (SEQ ID NO:
- 33), cyclic RGD {Fd}C (SEQ ID NO:
- 34), CGGRKRLQVQLSIRT (SEQ ID NO:
- 35), CIKVAV (SEQ ID NO:
- 36), CGGAASIKVAVSADR (SEQ ID NO:
- 37), CGGKRTGQYKL (SEQ ID NO:
- 38), CGGTYRSRKY (SEQ ID NO:
- 39), CGGYGGGP (GPP) 5GFOGERPP (GPP) 4GPC (SEQ ID NO:
- 40), CGGKRTGQYKLGSKTGPGQK (SEQ ID NO:
- 41), QAKHKQRKRLKSSC (SEQ ID NO:
- 42), SPKHHSQRARKKKNKNC (SEQ ID NO:
- 43), CGGXBBXBX, wherein B=basic residue and X=hydropathic residue (SEQ ID NO:
- 44), and CGGXBBBXXBX, wherein B=basic residue and X=hydropathic residue (SEQ ID NO:
- 45), or a combination thereof;
- wherein the crosslinking agent comprises a peptide having the sequence GCRDGPQG↓WGQDRCG (SEQ ID NO:
- 46), GCRDGPQG↓IAGQDRCG (SEQ ID NO:
- 47), GCRDVPMS↓MRGGDRCG (SEQ ID NO:
- 48), GCRDIPVS↓LRSGDRCG (SEQ ID NO:
- 49), GCRDRPFS↓MIMGDRCG (SEQ ID NO:
- 50), GCRDVPLS↓LTMGDRCG (SEQ ID NO:
- 51), GCRDVPLS↓LYSGDRCG (SEQ ID NO:
- 52), GCRDIPES↓LRAGDRCG (SEQ ID NO:
- 53), GCRDSGESPAY↓YTADRCG (SEQ ID NO:
- 54), GCRDGGYAE↓LRMGGDRCG (SEQ ID NO:
- 55), GCRDGGPLG↓LYAGGDRCG (SEQ ID NO:
- 56), or GCRDGPLG↓LWARDRCG SEQ ID NO:
- 57), 1,4-dithiothreitol poly (ethylene glycol) dithiol, or a combination thereof;
- wherein the pro-myogenic agent comprises muscle stem cells, muscle satellite cells, a pro-myogenic protein, or a combination thereof;
- and
- wherein C represents a group having the formula:
- wherein q is from 1-6.
69 more elements
Dependencies are inferred from the claim text.