CN117018289A - 一种手性骨水泥及其制备方法和应用 - Google Patents
一种手性骨水泥及其制备方法和应用 Download PDFInfo
- Publication number
- CN117018289A CN117018289A CN202311194766.3A CN202311194766A CN117018289A CN 117018289 A CN117018289 A CN 117018289A CN 202311194766 A CN202311194766 A CN 202311194766A CN 117018289 A CN117018289 A CN 117018289A
- Authority
- CN
- China
- Prior art keywords
- chiral
- bone cement
- bone
- solution
- liquid phase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000002639 bone cement Substances 0.000 title claims abstract description 120
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 67
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 37
- 239000005017 polysaccharide Substances 0.000 claims abstract description 37
- 150000004676 glycans Chemical class 0.000 claims abstract 11
- 239000007791 liquid phase Substances 0.000 claims description 42
- 230000007547 defect Effects 0.000 claims description 39
- 239000000243 solution Substances 0.000 claims description 39
- 238000003756 stirring Methods 0.000 claims description 39
- 239000011259 mixed solution Substances 0.000 claims description 36
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 26
- 239000007790 solid phase Substances 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 239000000853 adhesive Substances 0.000 claims description 17
- 230000001070 adhesive effect Effects 0.000 claims description 17
- 238000002156 mixing Methods 0.000 claims description 17
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 17
- 230000002378 acidificating effect Effects 0.000 claims description 16
- 239000001506 calcium phosphate Substances 0.000 claims description 16
- 239000007864 aqueous solution Substances 0.000 claims description 15
- 229960003638 dopamine Drugs 0.000 claims description 13
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 claims description 11
- 229910000150 monocalcium phosphate Inorganic materials 0.000 claims description 11
- 235000019691 monocalcium phosphate Nutrition 0.000 claims description 11
- 230000036571 hydration Effects 0.000 claims description 10
- 238000006703 hydration reaction Methods 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 9
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 8
- 239000012620 biological material Substances 0.000 claims description 8
- 239000011575 calcium Substances 0.000 claims description 8
- 229910052791 calcium Inorganic materials 0.000 claims description 8
- 230000001737 promoting effect Effects 0.000 claims description 7
- 239000003929 acidic solution Substances 0.000 claims description 5
- 239000003462 bioceramic Substances 0.000 claims description 5
- 235000011010 calcium phosphates Nutrition 0.000 claims description 5
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 5
- 229910021645 metal ion Inorganic materials 0.000 claims description 5
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 5
- 238000007711 solidification Methods 0.000 claims description 5
- 230000008023 solidification Effects 0.000 claims description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 230000000844 anti-bacterial effect Effects 0.000 claims description 3
- 229910010293 ceramic material Inorganic materials 0.000 claims description 3
- 230000035876 healing Effects 0.000 claims description 3
- 230000010478 bone regeneration Effects 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 239000000378 calcium silicate Substances 0.000 claims description 2
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 2
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 2
- 230000009920 chelation Effects 0.000 claims description 2
- 230000002188 osteogenic effect Effects 0.000 claims description 2
- VLCLHFYFMCKBRP-UHFFFAOYSA-N tricalcium;diborate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]B([O-])[O-].[O-]B([O-])[O-] VLCLHFYFMCKBRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract description 10
- 230000010354 integration Effects 0.000 abstract description 2
- 150000004804 polysaccharides Chemical class 0.000 description 26
- 229920002101 Chitin Polymers 0.000 description 17
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 10
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 230000008439 repair process Effects 0.000 description 9
- 230000008569 process Effects 0.000 description 7
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 5
- 229960005261 aspartic acid Drugs 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 238000011049 filling Methods 0.000 description 5
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 5
- 235000011090 malic acid Nutrition 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 230000000735 allogeneic effect Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 206010031264 Osteonecrosis Diseases 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000004043 dyeing Methods 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000017423 tissue regeneration Effects 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- 241000214032 Hedysarum Species 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000001142 circular dichroism spectrum Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 229960001270 d- tartaric acid Drugs 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 229960002989 glutamic acid Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 229940116298 l- malic acid Drugs 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 229940099690 malic acid Drugs 0.000 description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000011164 ossification Effects 0.000 description 2
- 230000002138 osteoinductive effect Effects 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000004080 punching Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- DYUQAZSOFZSPHD-SECBINFHSA-N (1r)-1-phenylpropan-1-ol Chemical compound CC[C@@H](O)C1=CC=CC=C1 DYUQAZSOFZSPHD-SECBINFHSA-N 0.000 description 1
- DYUQAZSOFZSPHD-VIFPVBQESA-N (1s)-1-phenylpropan-1-ol Chemical compound CC[C@H](O)C1=CC=CC=C1 DYUQAZSOFZSPHD-VIFPVBQESA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- SAUDSWFPPKSVMK-LBPRGKRZSA-N (2s)-2-(n-phenylanilino)propanoic acid Chemical group C=1C=CC=CC=1N([C@@H](C)C(O)=O)C1=CC=CC=C1 SAUDSWFPPKSVMK-LBPRGKRZSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UWTATZPHSA-N (R)-malic acid Chemical compound OC(=O)[C@H](O)CC(O)=O BJEPYKJPYRNKOW-UWTATZPHSA-N 0.000 description 1
- KWTSXDURSIMDCE-UHFFFAOYSA-N 1-phenylpropan-2-amine Chemical compound CC(N)CC1=CC=CC=C1 KWTSXDURSIMDCE-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 206010049824 Bone infarction Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- BDMCAOBQLHJGBE-UHFFFAOYSA-N C60-polyprenol Natural products CC(=CCCC(=CCCC(=CCCC(=CCCC(=C/CCC(=C/CCC(=C/CCC(=C/CCC(=C/CCC(=C/CCC(=C/CCC(=C/CO)C)C)C)C)C)C)C)C)C)C)C)C BDMCAOBQLHJGBE-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920001661 Chitosan Chemical class 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 229920000045 Dermatan sulfate Polymers 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 206010017088 Fracture nonunion Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 235000011201 Ginkgo Nutrition 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000237536 Mytilus edulis Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000002565 Open Fractures Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 229930186185 Polyprenol Natural products 0.000 description 1
- 229920001731 Polyprenol Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940023476 agar Drugs 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 239000012598 cell culture matrix Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
- 229940051593 dermatan sulfate Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000002082 fibula Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 150000002243 furanoses Chemical class 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002303 glucose derivatives Chemical class 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical class O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000005541 medical transmission Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 235000006109 methionine Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 235000020638 mussel Nutrition 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920000157 polyfructose Polymers 0.000 description 1
- 150000003096 polyprenols Chemical class 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 235000013930 proline Nutrition 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 150000003214 pyranose derivatives Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000007712 rapid solidification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000395 remineralizing effect Effects 0.000 description 1
- 229940016667 resveratrol Drugs 0.000 description 1
- 235000021283 resveratrol Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000003746 surface roughness Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 235000002374 tyrosine Nutrition 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 235000014393 valine Nutrition 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229920001221 xylan Polymers 0.000 description 1
- 150000004823 xylans Chemical class 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/10—Ceramics or glasses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0003—General processes for their isolation or fractionation, e.g. purification or extraction from biomass
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/38—Materials or treatment for tissue regeneration for reconstruction of the spine, vertebrae or intervertebral discs
Abstract
本发明属于生物医用材料领域,具体的涉及一种粘接性好,固化好,具有手性的骨水泥及其制备方法和应用。本发明通过手性分子修饰多糖的引入,制备出了具有适配性手性微环境的构造、其与机体骨之间的连接整合牢度强且能够快速固化,最终实现即刻种植的手性骨水泥。
Description
技术领域
本发明属于生物医用材料领域,具体的涉及一种粘接性好,固化好,具有手性多级结构的骨水泥及其制备方法和应用。
背景技术
宏观层面上,骨是全身最为坚硬的组织,支撑起身体,在和骨骼肌、神经系统的合作中促使运动行为的发生;微观层面上,骨骼组织根据其位置的不同,具有不同的发育模式和细胞组成特点。骨中的各种细胞具有感受力学刺激并将其转化为生物学信号的功能。骨缺损是由于创伤或手术而引起的骨质短缺,骨缺损常造成骨不连接,延迟愈合或不愈合,及局部的功能障碍。在病理过程中所造成的骨缺损,如创伤、炎症、骨病等因素所造成粉碎骨折、开放骨折大块骨组织缺损,炎症所致的骨坏死脱落分离,骨梗死或骨缺血性坏死所致大片骨坏死所造成的缺损等,这些都属于疾病所造成的骨缺损。
目前,治疗骨缺损的常用方法为自体骨或者同种异体骨移植,自体骨是目前公认的修复骨缺损的最佳方法,主要原因在于其具有良好的骨传导性、骨诱导性和生物相容性等,但是由于可获得性有限、有创的取骨过程和较高的供骨部位并发症,使自体骨移植的应用受到限制。同种异体骨虽然来源丰富,较易获得,但相对于自体骨,其缺乏良好的骨诱导性,成骨效果欠佳,并存在疾病传播和免疫排斥的风险。虽然组织具有一定的再生能力,但对于大面积骨缺损者,其修复能力较弱,缺损程度高于骨自身的修复能力,故而多需要采用临床干预治疗促使骨组织修复。传统治疗大段骨缺损主要有带血管蒂的腓骨移植技术、开放植骨技术(Papineau技术)、骨搬运技术(Ilizarov技术)等,但是这些技术治疗周期长,对技术要求也较高,较易出现骨折不愈合等并发症,临床运用受到一定的限制。由于自体骨来源有限,同种异体骨有着排斥反应、感染风险,故而以最大程度促进骨组织修复的仿生骨支架制备一直是临床医学和材料学领域的研究热点,生物支架逐渐成为一种有前途的骨修复和再生生物材料。
理想的骨修复材料应具有良好的生物相容性,对人体无毒无害,或低毒性;材料于成型满足不同移植部位的需要;合适的材料微结构来确保组织长入和营养供给;能够在体内被逐步降解和新骨代替。骨水泥是骨修复生物材料的成员之一,它通过固相和液相的理化和化学反应形成自固化。可以通过手术小切口,甚至经皮穿刺注射,将骨水泥送入治疗目标部位,使得治疗简单化和微创化,促进患者的康复。上世纪80年代,Brown和Chow博士研究再矿化糊剂来修复早期龋齿病变,研发出磷酸钙骨水泥(CPC),通过一种或几种磷酸钙盐化合物组成的固相与液相调和均匀成浆体,在生理条件下通过化学反应固化,最终在体内生物转化为羟基磷灰石(HAP),因其流动性佳、固化过程中放热少且骨传导作用及生物相容性良好、具有可降解性及可载药性等优点,在骨修复方面有重要应用价值。但是,现有制备磷酸钙骨水泥采用的固相均为普通结构的粉体或者是颗粒,普通结构的粉体或者颗粒形成的骨水泥不具备生物适配性,尤其是结构适配性这一重要的设计生物材料的因素,而导致治疗效果不理想。
在中国专利CN115364276B中,公开了一种负载红芪多糖的复合磷酸钙骨水泥,其制备方法为,混匀骨水泥的固相,将定量的红芪多糖溶解在骨水泥的液相中,按照液固比为0.6-1.5mL/g的比例将固相和液相置于80-95℃恒温水浴锅中不断搅拌进行糊化,塑形后待固化即可;然而忽略了骨组织的微观结构,以及对于骨缺损患者,不能实现即刻种植。又如在中国专利CN114105114B中,公开了一种工艺简单、成本低廉、具有多级手性结构且生物相容性好的手性介观结构羟基磷灰石薄膜的制备方法,用于作为细胞培养基质材料、干细胞分化诱导材料干细胞选择性分化诱导基质或靶向药物的载体,对于骨缺损患者,仍然不能满足能够即刻种植。
因此,具有生物适配性的生物材料是组织修复重建再生领域的关键所在。生物材料的孔隙、表面粗造度、拓扑形貌等结构是生物适配的重要因素。因此,调控材料的结构可以制备适配性好、性能优异的生物材料。手性是自然界的基本属性,普遍存在于生物体中,且与生命活动密切相关,如各种螺旋结构的DNA、蛋白质、细胞和组织等。多级结构是自然界中普遍存在的现象,由于材料具有多层次的组织结构,这赋予了材料意想不到的性能,天然骨就是一种手性多级结构组织。
生命体本身是一种手性多级结构,对手性的环境具有特异选择性。如手性药物在生命体内发挥着不同的作用,反应停是最典型的例子,还有一些手性农药也具有不同的杀虫作用。目前手性物质与生命体之间的关系也成为了研究的热点。本发明在制作骨水泥的过程中,通过添加手性分子,多糖衍生物,多巴胺以及有机酸等,实现手性多级结构适配性微环境的构造,固化强度好,粘接性强,并且能够即刻种植的性能。
发明内容
本发明采用无毒、可生物降解吸收的手性分子修饰多糖能够诱导骨水泥在水化过程中原位形成手性多级结构微环境;并且液相中的多糖衍生物在酸性环境下离子化增强了其与钙离子的螯合能力,从而产生化学键层面的粘结性;而多巴胺和手性分子共修饰的多糖衍生物仿生了贻贝蛋白中的粘接分子,从而产生氢键层面的粘接性。基于此,本发明制备的手性骨水泥实现了适配性手性微环境的构造、植入体骨水泥与机体骨之间的连接整合强牢度以及快速固化性能。
第一方面,本发明提供一种手性骨水泥,所述骨水泥是由固相与液相经水合固化反应获得,其中,骨水泥的液相成分含有手性多糖衍生物的酸性水溶液,骨水泥的固相成分含有钙基生物陶瓷材料,所述骨水泥具有粘接性和快固化的特点。
进一步的,所述钙基生物陶瓷材料包括但不限于羟基磷灰石、β-磷酸三钙、硅酸钙、硼酸钙、碳酸钙、硫酸钙、磷酸二氢钙和/或其它多种磷酸钙。
在一些实施方式中,所述钙基生物陶瓷材料选自β-磷酸三钙和磷酸二氢钙,其中β-磷酸三钙和磷酸二氢钙比例为:1:0.5~1。
进一步的,所述手性多糖衍生物的酸性水溶液是由如下步骤获得:
S001.将手性分子溶解于溶液中,然后再加入多糖,搅拌溶解、加热、结晶,形成混合溶液A;
S002.将多巴胺添加于混合溶液A中,形成混合溶液B;
S003.将多糖溶解于酸性溶液中充分搅拌溶解形成混合溶液C;
S004.将溶液B和溶液C按比例混合,得到最终的液相,即为手性多糖衍生物的酸性水溶液。
进一步的,所述液相中根据选用的手性分子构型不同,可以是D-型或L-型手性液相。
进一步的,所述手性分子为手性氨基酸、多肽分子、蛋白质分子、手性有机酸、手性糖类和手性醇类中的一种或多种。
更进一步的,所述手性氨基酸为组氨酸、精氨酸、赖氨酸、异亮氨酸、苯丙氨酸、亮氨酸、色氨酸、丙氨酸、甲硫氨酸、脯氨酸、半胱氨酸、天门冬氨酸、缬氨酸、丝氨酸、谷氨酰胺、酪氨酸、天门冬氨酸、谷氨酸、苏氨酸中的一种或多种;所述多肽分子为二苯丙氨酸;所述蛋白质分子为牛血清蛋白、可溶性胶原蛋白;所述手性有机酸为酒石酸、苹果酸、乳酸中的一种或多种;所述手性糖类为葡萄糖、果糖、半乳糖、核糖、脱氧核糖、呋喃糖、吡喃糖、麦芽糖、蔗糖、乳糖、透明质酸中的一种或多种;所述手性醇为甘露醇、木糖醇、山梨醇、紫杉醇、白藜芦醇、银杏叶聚戊烯醇、(R)-(+)-1-苯基-1-丙醇、(S)-(-)-1-苯基-1-丙醇、苯丙胺醇中的一种或几种。
进一步的,所述多糖包括但不限于淀粉、纤维素淀粉、纤维素、阿拉伯胶、果胶、半乳糖、几丁质(壳多糖)、多聚果糖、琼脂、透明质酸、硫酸软骨素、硫酸皮肤素、硫酸用层酸、肝素、硫酸乙酰肝素、海藻酸中的一种或多种。
进一步的,所述多糖衍生物包括但不限于纤维素衍生物、直链淀粉衍生物、木聚糖衍生物、菊糖衍生物、脱乙酰壳聚糖衍生物、葡萄糖衍生物中的一种或多种。
进一步的,所述酸性溶液包括但不限于草酸、柠檬酸、醋酸、碳酸、氢氟酸、丁二酸、苹果酸、葡萄糖酸、甲酸、乳酸、苯甲酸、丙烯酸、丙酸、硬脂酸、氢硫酸、次氯酸、硼酸中的一种或多种。
进一步的,所述手性分子与多糖的质量比例为:3~10:1~3。
进一步的,所述添加多巴胺的量为10~20mg/mL。
进一步的,所述酸性溶液中添加酸的量为2wt%~50wt%。
进一步的,所述溶液B和溶液C比例为:1~4:1~2。
进一步的,所述手性骨水泥液相与固相的比例为:1:0.2~1(质量g/体积mL)。
进一步的,在液相中可添加金属离子,作为骨水泥的抗菌功能或促骨生成功能元素。
更进一步的,所述金属离子包括但不限于Sr2+、Zn2+、Mn2+、Ga2+、Zn2+、Ag3+中的一种或多种。
第二方面,本发明提供一种如第一方面所述的手性骨水泥的制备方法,所述方法包括如下步骤:
步骤S1:制备含有手性多糖衍生物的酸性水溶液作为骨水泥的液相;
步骤S2:选用钙基生物陶瓷材料作为骨水泥的固相;
步骤S3:将步骤S2得到的骨水泥的固相与步骤S1得到的液相通过水合固化反应得到粘接性快固化手性骨水泥。
进一步,步骤S1的骨水泥液相包括如下步骤获得:
S001.将手性分子溶解于溶液中,然后再加入多糖,搅拌溶解、加热、结晶,形成混合溶液A;
S002.将多巴胺添加于混合溶液A中,形成混合溶液B;
S003.将多糖溶解于酸性溶液中充分搅拌溶解形成混合溶液C;
S004.将溶液B和溶液C按比例混合,得到最终的液相,即为手性多糖衍生物的酸性水溶液。
进一步的,所述手性分子与多糖的质量比例为:3~10:1~3。
进一步的,所述添加多巴胺的量为10~20mg/mL。
进一步的,所述酸性溶液中添加酸的量为2wt%~50wt%。
进一步的,所述溶液B和溶液C比例为:1~4:1~2。
进一步的,所述手性骨水泥液相与固相的比例为:1:0.2~1(质量g/体积mL)。
进一步的,在液相中可添加金属离子,作为骨水泥的抗菌功能或促骨生成功能元素。
更进一步的,所述金属离子包括但不限于Sr2+、Zn2+、Mn2+、Ga2+、Zn2+、Ag3+中的一种或多种。
第三方面,本发明提供一种如第一方面所述的手性骨水泥在制备治疗骨缺损医学生物材料中的应用,所述的应用为在制备提升固化性能、促进骨螯合、促进骨再生和骨愈合能力的骨水泥中的应用。
进一步的,所述骨缺损是指由于各种原因导致的正常骨质的缺失。
进一步的,所述骨缺损包括但不限于创伤性骨缺损、先天性骨缺损、感染性骨缺损中的一种或多种。
进一步的,所述骨缺损包括但不限于牙槽骨缺损、颅骨缺损、股骨头坏死缺损、肿瘤骨坏死缺损、脊柱骨缺损等。
附图说明
图1粘接性手性骨水泥的制备流程图;
图2粘接性手性骨水泥的粘性展示图;
图3猪骨缺损模型中粘接性手性骨水泥在缺损部位填充固化;
图4猪骨缺损模型中粘接性手性骨水泥在缺损部位填充固化30分钟后的打孔性;
图5实施例1中制备的粘接性手性骨水泥的手性信号。
具体实施方式
下面将结合实施例,对本发明的技术方案进行清楚、完整地描述,但不作为本发明的限定,然所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有作出创造性劳动的前提下所获得的所有其他实施例,都属于本发明保护的范围。需要说明的是,在不冲突的情况下,本发明中的实施例及实施例中的特征可以相互组合。
为使本发明的目的、优点和特征更加清楚,以下对本发明提出的粘接性手性骨水泥及其制备方法作进一步详细说明。需说明的是,附图均采用非常简化的形式且均使用非常精准的比例,仅用以方便、明晰地辅助说明本发明实施例的目的。
实施例1:手性骨水泥制品1
本实施例的骨水泥制品通过如下方法制备获得(见图1),所述方法的步骤如下:
步骤S1:制备含有手性多糖衍生物的酸性水溶液作为骨水泥的液相;
S001.将手性分子L-酒石酸分子溶解于纯水中,然后再加入壳多糖,L-酒石酸与壳多糖的质量百分比为7.5:2,经过充分搅拌溶解,然后加热到30℃继续搅拌6小时,进行溶液中热结晶反应,形成混合溶液A;
S002.将10mg/mL的多巴胺添加于混合溶液A中,经过充分搅10分钟拌和紫外辐照2分钟,形成混合溶液B;
S003.将壳多糖溶解于40wt%的柠檬酸溶液中,充分搅拌溶解形成混合溶液C;
S004.将溶液B和溶液C按体积比3:2混合,室温下搅拌20分钟,得到骨水泥的液相。
步骤S2:选用以β-磷酸三钙和磷酸二氢钙的质量比为1:0.67,作为骨水泥的固相;
步骤S3:将步骤S2得到的骨水泥的固相与步骤S1得到的液相以1:0.33质量g/体积mL的比例通过水合固化反应得到粘接性快固化手性骨水泥。
同理,手性分子可选用D-酒石酸,最后获得D-型的手性骨水泥。
结果见图2~图5,图2为本施例粘接性手性骨水泥的粘性展示图,图中可见手性骨水泥像口香糖一样,粘稠可拉丝,具有粘性;图3为猪骨缺损模型中粘接性手性骨水泥在缺损部位填充固化,图中显示,将混合好的骨水泥填充在骨缺损部位,很快就可以成型,且全完填充缺损区域;图4为猪骨缺损模型中粘接性手性骨水泥在缺损部位填充固化30分钟后的打孔性,图中显示,经过三十分钟的固化反应,骨水泥以及达到了相当的强度,可在其填充部位进行打孔,获得的孔均匀稳定且具有很好的形状,不会裂开;图5为制备的粘接性手性骨水泥的圆二色光谱信号即手性信号,图中为用L-酒石酸修饰的多糖形成的手性骨水泥的CD谱,可以看到在200-800纳米波段范围内有两个负向的鼓包峰,对应于手性骨水泥内部的不同级别的手性结构。
实施例2:手性骨水泥制品2
本实施例的骨水泥制品通过如下方法制备获得,所述方法的步骤如下:
步骤S1:制备含有手性多糖衍生物的酸性水溶液作为骨水泥的液相;
S001.将手性分子L-苹果酸分子溶解于纯水中,然后再加入壳多糖,L-苹果酸与壳多糖的质量百分比为3:1,经过充分搅拌溶解,然后加热到40℃继续搅拌5小时,进行溶液中热结晶反应,形成混合溶液A;
S002.将15mg/mL的多巴胺添加于混合溶液A中,经过充分搅5分钟拌和紫外辐照6分钟,形成混合溶液B;
S003.将壳多糖溶解于30wt%的柠檬酸溶液中充分搅拌溶解形成混合溶液C;
S004.将溶液B和溶液C按体积比1:1的比例混合,室温下搅拌60分钟,得到骨水泥的液相。
步骤S2:选用以β-磷酸三钙和磷酸二氢钙的质量比为1:0.67,作为骨水泥的固相;
步骤S3:将步骤S2得到的骨水泥的固相与步骤S1得到的液相以1:0.4质量g/体积mL的比例通过水合固化反应得到粘接性快固化手性骨水泥。
同理,手性分子可选用D-苹果酸,最后获得D-型的手性骨水泥。
实施例3手性骨水泥制品3
本实施例的骨水泥制品通过如下方法制备获得,所述方法的步骤如下:
步骤S1:制备含有手性多糖衍生物的酸性水溶液作为骨水泥的液相;
S001.将手性分子L-酒石酸分子溶解于纯水中,然后再加入壳多糖,L-酒石酸与壳多糖的质量百分比为4:1,经过充分搅拌溶解,然后加热到50℃继续搅拌4小时,进行溶液中热结晶反应,形成混合溶液A;
S002.将20mg/mL的多巴胺添加于混合溶液A中,经过充分搅10分钟拌和紫外辐照3分钟,形成混合溶液B;
S003.将壳多糖溶解于20wt%的草酸溶液中,充分搅拌溶解形成混合溶液C;
S004.将溶液B和溶液C按体积比4:1的比例混合,室温下搅拌40分钟,得到骨水泥的液相。
步骤S2:选用以β-磷酸三钙和磷酸二氢钙的质量比为1:0.5,作为骨水泥的固相;
步骤S3:将步骤S2得到的骨水泥的固相与步骤S1得到的液相以1:0.25质量g/体积mL的比例通过水合固化反应得到粘接性快固化手性骨水泥。
同理,手性分子可选用D-酒石酸,最后获得D-型的手性骨水泥。
实施例4手性骨水泥制品4
本实施例的骨水泥制品通过如下方法制备获得,所述方法的步骤如下:
步骤S1:制备含有手性多糖衍生物的酸性水溶液作为骨水泥的液相;
S001.将手性分子L-天冬氨酸分子溶解于纯水中,然后再加入壳多糖,L-天冬氨酸与壳多糖的质量百分比为9:2,经过充分搅拌溶解,然后加热到60℃继续搅拌3小时,进行溶液中热结晶反应,形成混合溶液A;
S002.将12mg/mL的多巴胺添加于混合溶液A中,经过充分搅8分钟拌和紫外辐照2分钟,形成混合溶液B;
S003.将壳多糖溶解于20wt%的草酸溶液中充分搅拌溶解形成混合溶液C;
S004.将溶液B和溶液C按体积比2:1的比例混合,室温下搅拌80分钟,得到骨水泥的液相。
步骤S2:选用以β-磷酸三钙和磷酸二氢钙的质量比为1:0.75,作为骨水泥的固相;
步骤S3:将步骤S2得到的骨水泥的固相与步骤S1得到的液相以1:0.4质量g/体积mL的比例通过水合固化反应得到粘接性快固化手性骨水泥。
同理,手性分子可选用D-天冬氨酸,最后获得D-型的手性骨水泥。
实施例5手性骨水泥制品5
本实施例的骨水泥制品通过如下方法制备获得,所述方法的步骤如下:
步骤S1:制备含有手性多糖衍生物的酸性水溶液作为骨水泥的液相;
S001.将手性分子L-谷氨酸分子溶解于纯水中,然后再加入壳多糖,L-天冬氨酸与壳多糖的质量百分比为5:1,经过充分搅拌溶解,然后加热到70℃继续搅拌1小时,进行溶液中热结晶反应,形成混合溶液A;
S002.将10mg/mL的多巴胺添加于混合溶液A中,经过充分搅10分钟拌和紫外辐照1分钟,形成混合溶液B;
S003.将壳多糖溶解于2wt%的醋酸溶液中充分搅拌溶解形成混合溶液C;
S004.将溶液B和溶液C按体积比3:1的比例混合,室温下搅拌120分钟,得到骨水泥的液相。
步骤S2:选用以β-磷酸三钙和磷酸二氢钙的质量比为1:1,作为骨水泥的固相;
步骤S3:将步骤S2得到的骨水泥的固相与步骤S1得到的液相以1:0.75质量g/体积mL的比例通过水合固化反应得到粘接性快固化手性骨水泥。
同理,手性分子可选用D-天冬氨酸,最后获得D-型的手性骨水泥。
实施6手性骨水泥的细胞增值粘附实验
本测试例中采用实施例1的D型、L型的手性骨水泥进行细胞的粘附增殖分化实验,所采用的细胞株为骨髓来源的间充质干细胞(BMSC)。
粘附增殖实验具体操作过程如下:
1)首先将灭菌消毒好的手性骨水泥铺在细胞培养板的底部;
2)然后分别将分散好的上BMSC细胞种在手性基底上,进行培养;
3)培养一段时间后,取出培养板,然后用PBS洗,用4%的PFA进行固定;
4)固定好后用PBS多洗几次,然后进行染色;
5)最后在显微镜下进行观察、拍照。
分化实验具体操作过程如下:
1)首先从小鼠的股骨z中提取骨髓来源的间充质干细胞,进行培养和孵化;
2)然后进行种植,先将灭菌消毒好的骨水泥基底铺在细胞培养板的底部;
3)将分散好的上BMSC细胞种在手性骨水泥基底上,进行培养;
3)培养一段时间后,取出培养板,然后用PBS洗,用4%的PFA进行固定;
4)固定好后用PBS多洗几次,然后进行油红染色和ALP染色;
5)最后在显微镜下进行观察、拍照。
实施7手性骨水泥的牙槽骨的植入实验
本测试例中采用实施例1的D型、L型的手性骨水泥进行牙槽骨的缺损修复和即刻种植实验,所采用的动物为比格犬。
具体操作过程如下:
1)首先比格犬牙槽骨缺损造模;
2)然后进行种植,先将灭菌消毒好的手性骨水泥进行混合均匀;
3)然后将混合好的骨水泥填充在牙槽骨缺损部位,进行原位固化;
4)固化一段时间后,确认强度是否达到可打孔的程度,然后就可以打孔植入螺装,然后培养修复一段时间;
5)取出样本观察骨缺损修复情况。
Claims (10)
1.一种手性骨水泥,所述骨水泥是由固相与液相经水合固化反应获得,其中,骨水泥的液相成分含有手性多糖衍生物的酸性水溶液,骨水泥的固相成分含有钙基生物陶瓷材料,所述骨水泥具有粘接性和快固化的特点。
2.如权利要求1所述的手性骨水泥,其特征在于,所述钙基生物陶瓷材料选自羟基磷灰石、β-磷酸三钙、硅酸钙、硼酸钙、碳酸钙、硫酸钙、磷酸二氢钙和/或其它多种磷酸钙。
3.如权利要求1所述的手性骨水泥,其特征在于,所述钙基生物陶瓷材料选自β-磷酸三钙和磷酸二氢钙,其中β-磷酸三钙和磷酸二氢钙比例为:1:0.5~1。
4.如权利要求1所述的手性骨水泥,其特征在于,所述手性多糖衍生物的酸性水溶液是由如下步骤获得:
S001.将手性分子溶解于溶液中,然后再加入多糖,搅拌溶解、加热、结晶,形成混合溶液A;
S002.将多巴胺添加于混合溶液A中,形成混合溶液B;
S003.将多糖溶解于酸性溶液中充分搅拌溶解形成混合溶液C;
S004.将溶液B和溶液C按比例混合,得到最终的液相,即为手性多糖衍生物的酸性水溶液。
5.如权利要求4所述的手性骨水泥,其特征在于,所述手性分子与多糖的质量比例为:3~10:1~3。
6.如权利要求4所述的手性骨水泥,其特征在于,所述手性骨水泥液相与固相的比例为:1:0.2~1(质量g/体积mL)。
7.如权利要求4所述的手性骨水泥,其特征在于,在液相中可添加金属离子,作为骨水泥的抗菌功能或促骨生成功能元素,所述金属离子选自Sr2+、Zn2+、Mn2+、Ga2+、Zn2+、Ag3+中的一种或多种。
8.一种如权利要求1所述的手性骨水泥的制备方法,所述方法包括如下步骤:
步骤S1:制备含有手性多糖衍生物的酸性水溶液作为骨水泥的液相;
步骤S2:选用钙基生物陶瓷材料作为骨水泥的固相;
步骤S3:将步骤S2得到的骨水泥的固相与步骤S1得到的液相通过水合固化反应得到粘接性快固化手性骨水泥。
9.如权利要求8所述的手性骨水泥的制备方法,其特征在于,步骤S1的骨水泥液相包括如下步骤获得:
S001.将手性分子溶解于溶液中,然后再加入多糖,搅拌溶解、加热、结晶,形成混合溶液A;
S002.将多巴胺添加于混合溶液A中,形成混合溶液B;
S003.将多糖溶解于酸性溶液中充分搅拌溶解形成混合溶液C;
S004.将溶液B和溶液C按比例混合,得到最终的液相,即为手性多糖衍生物的酸性水溶液。
10.一种如权利要求1所述的手性骨水泥在制备治疗骨缺损医学生物材料中的应用,所述的应用为在制备提升固化性能、促进骨螯合、促进骨再生和骨愈合能力的骨水泥中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202311194766.3A CN117018289A (zh) | 2023-09-15 | 2023-09-15 | 一种手性骨水泥及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202311194766.3A CN117018289A (zh) | 2023-09-15 | 2023-09-15 | 一种手性骨水泥及其制备方法和应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN117018289A true CN117018289A (zh) | 2023-11-10 |
Family
ID=88626652
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202311194766.3A Pending CN117018289A (zh) | 2023-09-15 | 2023-09-15 | 一种手性骨水泥及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN117018289A (zh) |
-
2023
- 2023-09-15 CN CN202311194766.3A patent/CN117018289A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6139578A (en) | Preparation of cell seeded ceramic compositions | |
CN101057979B (zh) | 可注射自固化磷酸钙骨组织修复材料及其制备方法与应用 | |
Link et al. | Mechanical evaluation of implanted calcium phosphate cement incorporated with PLGA microparticles | |
JP5759370B2 (ja) | 組織工学および骨の再生のための、構造化された多孔率を有するモネタイトの三次元マトリクス、および、当該三次元マトリクスの調製方法 | |
CN106215225B (zh) | 一种医用的骨创面止血材料及其制备方法 | |
CN110665063A (zh) | 3d生物打印墨水及其制备方法、组织工程支架及其制备方法 | |
CN104853742A (zh) | 用于治疗用途的基于交联透明质酸和羟基磷灰石的可注射无菌水性制剂 | |
CN112023120B (zh) | 一种可注射预灌装骨修复颗粒及其制备方法和应用 | |
CN105749356B (zh) | 活性多糖复合骨修复材料 | |
Ana | Bone substituting materials in dental implantology | |
Qi et al. | Development and characterization of an injectable cement of nano calcium-deficient hydroxyapatite/multi (amino acid) copolymer/calcium sulfate hemihydrate for bone repair | |
Hulsart-Billström et al. | In vivo safety assessment of a bio-inspired bone adhesive | |
CN111973797B (zh) | 一种骨科用无创植入高黏度胶材料及其制备方法及应用 | |
CN101954122A (zh) | 具有预塑性天然骨修复材料的制备方法 | |
CN114452441A (zh) | 一种颅骨修复聚醚醚酮材料及其制备方法 | |
Mansouri et al. | The role of cuttlebone and cuttlebone derived hydroxyapatite with platelet rich plasma on tibial bone defect healing in rabbit: An experimental study | |
CN112494712A (zh) | 一种具有止血和促骨愈合功能的可吸收海绵状骨蜡及其制备方法 | |
CN114302748A (zh) | 衍生自有孔虫的骨移植材料 | |
Mills | The role of polymer additives in enhancing the response of calcium phosphate cement | |
CN117018289A (zh) | 一种手性骨水泥及其制备方法和应用 | |
CN105031727A (zh) | 一种载药复合骨修复材料及其制备方法 | |
RU2494721C1 (ru) | Биосовместимый костнозамещающий материал и способ получения его | |
CN114533950A (zh) | 一种用于骨缺损修复的生物陶瓷-金属组合体及其制备方法 | |
CN1158109C (zh) | 生物复合人工骨及其制备工艺 | |
CN1413738A (zh) | 软质人工骨材料 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |