WO1997014783B1 - Tissue-engineered bone repair using cultured periosteal cells - Google Patents
Tissue-engineered bone repair using cultured periosteal cellsInfo
- Publication number
- WO1997014783B1 WO1997014783B1 PCT/US1996/016664 US9616664W WO9714783B1 WO 1997014783 B1 WO1997014783 B1 WO 1997014783B1 US 9616664 W US9616664 W US 9616664W WO 9714783 B1 WO9714783 B1 WO 9714783B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cells
- matrix
- composition
- periosteal
- bone
- Prior art date
Links
- 210000000988 bone and bone Anatomy 0.000 title claims 8
- 230000007547 defect Effects 0.000 claims abstract 5
- 239000011159 matrix material Substances 0.000 claims 11
- 239000000203 mixture Substances 0.000 claims 10
- 238000000034 method Methods 0.000 claims 8
- 230000001939 inductive effect Effects 0.000 claims 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 4
- 102000004190 Enzymes Human genes 0.000 claims 4
- 108090000790 Enzymes Proteins 0.000 claims 4
- 230000002708 enhancing effect Effects 0.000 claims 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims 4
- 230000011164 ossification Effects 0.000 claims 4
- 239000000411 inducer Substances 0.000 claims 3
- 210000001519 tissue Anatomy 0.000 claims 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 2
- 229930003268 Vitamin C Natural products 0.000 claims 2
- 229930003316 Vitamin D Natural products 0.000 claims 2
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 claims 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims 2
- 230000002308 calcification Effects 0.000 claims 2
- 230000008021 deposition Effects 0.000 claims 2
- 229960003957 dexamethasone Drugs 0.000 claims 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims 2
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 claims 2
- 229960002986 dinoprostone Drugs 0.000 claims 2
- 229960002061 ergocalciferol Drugs 0.000 claims 2
- 229960000890 hydrocortisone Drugs 0.000 claims 2
- 239000000017 hydrogel Substances 0.000 claims 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims 2
- 238000002513 implantation Methods 0.000 claims 2
- 239000000463 material Substances 0.000 claims 2
- 229920005615 natural polymer Polymers 0.000 claims 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims 2
- 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 2
- 229910052698 phosphorus Inorganic materials 0.000 claims 2
- 239000011574 phosphorus Substances 0.000 claims 2
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 claims 2
- 150000003180 prostaglandins Chemical class 0.000 claims 2
- 150000003431 steroids Chemical class 0.000 claims 2
- 229920001059 synthetic polymer Polymers 0.000 claims 2
- 229930003231 vitamin Natural products 0.000 claims 2
- 235000013343 vitamin Nutrition 0.000 claims 2
- 239000011782 vitamin Substances 0.000 claims 2
- 229940088594 vitamin Drugs 0.000 claims 2
- 235000019154 vitamin C Nutrition 0.000 claims 2
- 239000011718 vitamin C Substances 0.000 claims 2
- 235000019166 vitamin D Nutrition 0.000 claims 2
- 239000011710 vitamin D Substances 0.000 claims 2
- 150000003710 vitamin D derivatives Chemical class 0.000 claims 2
- 235000001892 vitamin D2 Nutrition 0.000 claims 2
- 239000011653 vitamin D2 Substances 0.000 claims 2
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 claims 2
- 229940046008 vitamin d Drugs 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 230000004069 differentiation Effects 0.000 claims 1
- 239000001963 growth medium Substances 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 229920002683 Glycosaminoglycan Polymers 0.000 abstract 1
- 102000004067 Osteocalcin Human genes 0.000 abstract 1
- 108090000573 Osteocalcin Proteins 0.000 abstract 1
- 238000010256 biochemical assay Methods 0.000 abstract 1
- 238000004113 cell culture Methods 0.000 abstract 1
- 239000007943 implant Substances 0.000 abstract 1
- 230000001582 osteoblastic effect Effects 0.000 abstract 1
Abstract
Periosteal cells have been grown in cell culture and have been shown to have an osteoblastic phenotype, with production of osteocalcin and glycosaminoglycan. When seeded into polymeric implants, repair of critical size cranial defects was demonstrated and was confirmed by histology, biochemical assays, and radiodensitometry.
Claims
AMENDED CLAIMS
[received by the International Bureau on 10 April 1997 (1004.97), original claims 1-15 replaced by amended claims 1-15 (2 pages)]
1 A method for making a composition for repair of bone defects consisting essentially of obtaining periosteal tissue, dissociating the cells in the periosteal tissue, and culturing the cells on and in a biocompatible matrix suitable for repair of the defect under conditions inducing the periosteal cells to form bone
2 The method of claim 1 wherein the matrix is formed of a material selected from the group consisting of hydroxyapatite, synthetic polymers, natural polymers, and mixtures thereof
3 The method of claim 1 wherein the matrix is biodegradable
4 The method of claim 1 wherein the matrix is a hydrogel
5 The method of claim 1 wherein the matrix in combination with the implantation substrate induce the periosteal cells to differentiate into bone
6 The method of claim 1 wherein the cells are cultured in vitro prior to implantation under conditions inducing differentiation of the periosteal cells into bone
7 The method of claim 6 wherein the periosteal cells are cultured in media comprising inducers of osteogenesis selected from the group consisting of steroids inducing bone formation, enzymes enhancing calcification, enzymes enhancing phosphorus deposition, vitamins, and prostaglandins
8 The method of claim 7 wherein the inducers are selected from the group consisting of dexamethasone, calciferol, cortisol, vitamin C, vitamin D, and prostaglandin E2
9 A composition for repair of bone defects consisting essentially of cells obtained by dissociating periosteal tissue, wherein the cells are seeded on and in a biocompatible matrix suitable for repair of the defect, and culture conditions inducing the periosteal cells to form bone
10. The composition of claim 9 wherein Lhe matrix is formed of a material selected from the group consisting of hydroxyapatite, synthetic polymers, natural polymers, and mixtures thereof.
11. The composition of claim 9 wherein the matrix is biodegradable.
12. The composition of claim 10 wherein the matrix is a hydrogel.
13. The composition of claim 9 wherein the matrix induces the periosteal cells to differentiate into bone.
14. The composition of claim 9 wherein the periosteal cells are cultured on the matrix in a culture media comprising inducers of osteogenesis selected from the group consisting of steroids inducing bone formation, enzymes enhancing calcification, enzymes enhancing phosphorus deposition, vitamins, and prostaglandins.
15. The composition of claim 14 wherein the compounds are selected from the group consisting of dexamethasone, calciferol, cortisol, vitamin C, vitamin D, and prostaglandin E2.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU74515/96A AU7451596A (en) | 1995-10-20 | 1996-10-17 | Tissue-engineered bone repair using cultured periosteal cells |
| EP96936643A EP0862617A1 (en) | 1995-10-20 | 1996-10-17 | Tissue-engineered bone repair using cultured periosteal cells |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US545,988 | 1990-06-28 | ||
| US08/545,988 US5700289A (en) | 1995-10-20 | 1995-10-20 | Tissue-engineered bone repair using cultured periosteal cells |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1997014783A1 WO1997014783A1 (en) | 1997-04-24 |
| WO1997014783B1 true WO1997014783B1 (en) | 1997-05-22 |
Family
ID=24178377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1996/016664 WO1997014783A1 (en) | 1995-10-20 | 1996-10-17 | Tissue-engineered bone repair using cultured periosteal cells |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US5700289A (en) |
| EP (1) | EP0862617A1 (en) |
| AU (1) | AU7451596A (en) |
| WO (1) | WO1997014783A1 (en) |
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| IL74617A (en) * | 1985-03-15 | 1988-11-15 | Yeda Res & Dev | Compositions comprising a vitamin d derivative and method for the local treatment of bone fractures in animals |
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| US5439951A (en) * | 1993-03-24 | 1995-08-08 | Children's Medical Center Corporation | Isolation of the calcium-phosphate crystals of bone |
| ATE180674T1 (en) * | 1993-03-29 | 1999-06-15 | Zymogenetics Inc | OSTEOBLAST GROWTH-SUPPORTING COMPOSITIONS THAT CONTAIN PDGF AND VITAMIN-D |
| US5518680A (en) * | 1993-10-18 | 1996-05-21 | Massachusetts Institute Of Technology | Tissue regeneration matrices by solid free form fabrication techniques |
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1996
- 1996-10-17 AU AU74515/96A patent/AU7451596A/en not_active Abandoned
- 1996-10-17 WO PCT/US1996/016664 patent/WO1997014783A1/en not_active Application Discontinuation
- 1996-10-17 EP EP96936643A patent/EP0862617A1/en not_active Withdrawn
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