Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine...

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Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable Composite Polymer*† by JAMES D. HECKMAN, WILLIAM EHLER, BRYAN P. BROOKS, THOMAS B. AUFDEMORTE, CHRISTOPH H. LOHMANN, THANE MORGAN, and BARBARA D. BOYAN J Bone Joint Surg Am Volume 81(12):1717-29 December 1, 1999 ©1999 by The Journal of Bone and Joint Surgery, Inc.

Transcript of Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine...

Page 1: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal

Nonunions Implanted with a Biodegradable Composite Polymer*†

by JAMES D. HECKMAN, WILLIAM EHLER, BRYAN P. BROOKS, THOMAS B. AUFDEMORTE, CHRISTOPH H. LOHMANN, THANE MORGAN, and BARBARA D.

BOYAN

J Bone Joint Surg AmVolume 81(12):1717-29

December 1, 1999

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 2: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 1 Photograph of a three-millimeter-thick microporous-macroporous polylactic acid-polyglycolic acid carrier.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 3: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Figs. 2-A through 2-D: Radiographs of the radius of a fourteen-kilogram dog that was treated with implantation of a polylactic acid-polyglycolic acid carrier without growth factors (group A).

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 4: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 2-B Three months after the ostectomy, moderately hypertrophic nonunion was evident.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 5: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 2-C Immediately after implantation of the carrier.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 6: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 2-D Three months after implantation of the carrier, no bone-healing was evident and the plate was broken, indicative of persistent motion at the site of the nonunion.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 7: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Figs. 3-A through 3-D: Radiographs of the radius of a thirteen-kilogram dog that was treated with implantation of a polylactic acid-polyglycolic acid carrier with fifteen milligrams of BMP (group

D).

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 8: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 3-B Three months after the ostectomy, hypertrophic nonunion was evident.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 9: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 3-C Immediately after implantation of the carrier.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 10: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 3-D Twelve weeks after implantation of the carrier, there was clear evidence of complete endosteal bridging and some evidence of periosteal bridging.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 11: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Figs. 4-A through 4-E: Photomicrographs of paraffin-embedded sections of specimens from the five groups (hematoxylin and eosin; original magnification, x 16).

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 12: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 4-B Specimen treated with fifteen milligrams of BMP (group B), showing substantial healing, particularly of the upper 50 percent of the specimen.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 13: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 4-C Specimen treated with 1.5 milligrams of BMP (group C), showing a moderate amount of residual matrix persisting in the upper 50 percent of the nonunion site.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 14: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 4-D Specimen treated with ten nanograms of TGF-β1 combined with fifteen milligrams of BMP (group D), showing appreciable healing.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.

Page 15: Bone Morphogenetic Protein But Not Transforming Growth Factor-β Enchances Bone Formation in Canine Diaphyseal Nonunions Implanted with a Biodegradable.

Fig. 4-E Specimen treated with ten nanograms of TGF-β1 alone (group E), showing fibrous connective tissue with inflammation and focal residual carrier and no bridging of the defect site.

JAMES D. HECKMAN et al. J Bone Joint Surg Am 1999;81:1717-29

©1999 by The Journal of Bone and Joint Surgery, Inc.