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Edgar G. Dawson - One of the best experts on this subject based on the ideXlab platform.

  • experimental spinal fusion with recombinant human Bone Morphogenetic Protein 2 without decortication of osseous elements
    Spine, 1997
    Co-Authors: Haramol Singh Sandhu, Linda E A Kanim, J. Michael Kabo, J. M. Toth, Rick B. Delamarter, Edgar G. Dawson
    Abstract:

    STUDY DESIGN: L4-L5 intertransverse process fusions were produced with 58 micrograms, 230 micrograms, or 920 micrograms of recombinant human Bone Morphogenetic Protein-2 in 20 dogs. Eleven had traditional decortication of posterior elements before insertion of the implant. Nine were left undecorticated. All animals were evaluated 3 months after surgery. OBJECTIVES: To determine whether decortication is a prerequisite for successful fusion in the presence of osteoinductive Proteins such as Bone Morphogenetic Protein-2. SUMMARY OF BACKGROUND DATA: Recombinant osteoinductive Proteins can induce de novo Bone in ectopic soft-tissue sites in the absence of Bone marrow elements. Traditional methods for achieving spinal fusion rely on exposure of Bone marrow through decortication to facilitate osteogenesis. It is hypothesized that the presence of an implanted osteoinductive Protein obviates the need for exposure and release of host inductive factors. METHODS: Recombinant human Bone Morphogenetic Protein-2-induced intertransverse process fusions were performed with and without decortication. Fusion sites were evaluated by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis. RESULTS: One hundred percent of decorticated spines and 89% of undecorticated spines were clinically fused by 3 months. Ninety-one percent of decorticated spines and 78% of undecorticated specimens exhibited bilateral transverse process osseous bridging. The only spines that failed to achieve solid bilateral arthrodesis were in the lowest dose group. With the higher two doses, there was histologic evidence of osseous continuity between the fusion mass and undecorticated transverse processes. CONCLUSIONS: There were no statistical differences in clinical and radiographic fusion rates between decorticated and undecorticated sites. With higher doses of recombinant human Bone morphoganetic Protein-2, there was little histologic distinction between fusions in decorticated versus undecorticated spines.

  • Effective doses of recombinant human Bone Morphogenetic Protein-2 in experimental spinal fusion
    Spine, 1996
    Co-Authors: Haramol Singh Sandhu, Erik N Zeegen, Linda E A Kanim, J. Michael Kabo, J. M. Toth, Rick B. Delamarter, D. Liu, Edgar G. Dawson
    Abstract:

    STUDY DESIGN: Nineteen dogs underwent L4-L5 intertransverse process fusions with either 58 micrograms, 115 micrograms, 230 micrograms, 460 micrograms, or 920 micrograms of recombinant human Bone Morphogenetic Protein-2 carried by a polylactic acid polymer. A previous study (12 dogs) compared 2300 micrograms of recombinant human Bone Morphogenetic Protein-2, autogenous iliac Bone, and carrier alone in this model. All fusions subsequently were compared. OBJECTIVES: To characterize the dose-response relationship of recombinant human Bone Morphogenetic Protein-2 in a spinal fusion model. SUMMARY OF BACKGROUND DATA: Recombinant osteoinductive morphogens, such as recombinant human Bone Morphogenetic Protein-2, are effective in vertebrate diaphyseal defect and spinal fusion models. It is hypothesized that the quality of spinal fusion produced with recombinant human Bone Morphogenetic Protein-2, above a threshold dose, does not change with increasing amounts of inductive Protein. METHODS: After decortication of the posterior elements, the designated implants were placed along the intertransverse process space bilaterally. The fusion sites were evaluated after 3 months by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis. RESULTS: As in the study using 2300 micrograms of recombinant human Bone Morphogenetic Protein-2, implantation of 58-920 micrograms of recombinant human Bone Morphogenetic Protein-2 successfully resulted in intertransverse process fusion in the dog by 3 months. This had not occurred in animals containing autograft or carrier alone. The cross-sectional area of the fusion mass and mechanical stiffness of the L4-L5 intersegment were not dose-dependent. Histologic findings varied but were not related to rhBMP-2 dose. Inflammatory reaction to the composite implant was proportional inversely to the volume of the fusion mass. CONCLUSIONS: No mechanical, radiographic, or histologic differences in the quality of intertransverse process fusion resulted from a 40-fold variation in dose of recombinant human Bone Morphogenetic Protein-2.

Marshall R. Urist - One of the best experts on this subject based on the ideXlab platform.

  • The Classic: Bone Morphogenetic Protein
    Clinical Orthopaedics and Related Research®, 2009
    Co-Authors: Marshall R. Urist, Basil S. Strates
    Abstract:

    This Classic Article is a reprint of the original work by Marshall R. Urist and Basil S. Strates, Bone Morphogenetic Protein. An accompanying biographical sketch of Marshall R. Urist, MD is available at DOI 10.1007/s11999-009-1067-4; a second Classic Article is available at DOI 10.1007/s11999-009-1069-2; and a third Classic Article is available at DOI 10.1007/s11999-009-1070-9. The Classic Article is copyright 1971 by Sage Publications Inc. Journals and is reprinted with permission from Urist MR, Strates BS. Bone Morphogenetic Protein. J Dent Res. 1971;50:1392-1406.

  • Healing of a Scaphoid Nonunion Using Human Bone Morphogenetic Protein
    The Journal of Hand Surgery, 2005
    Co-Authors: Neil F. Jones, Erin E. Brown, Amir Mostofi, Esther Vögelin, Marshall R. Urist
    Abstract:

    A chronic nonunion of a proximal pole fracture of the scaphoid was treated by curettage of the nonunion, single K-wire fixation, and implantation of 50 mg of human Bone Morphogenetic Protein followed by 12 weeks of cast immobilization without any conventional corticocancellous Bone grafting or rigid screw fixation. Radiographs showed signs of bony healing by 12 weeks and a magnetic resonance imaging scan 6 years after surgery showed no signs of avascular necrosis. The potential future applications of human Bone Morphogenetic Protein in hand surgery are discussed.

  • Human Bone Morphogenetic Protein allografting for reconstruction of femoral nonunion
    Clinical Orthopaedics and Related Research, 2000
    Co-Authors: Eric E. Johnson, Marshall R. Urist
    Abstract:

    A composite inductive allograft consisting of an allogeneic, autolysed, antigen-free cortical Bone carrier lyophilized with partially purified human Bone Morphogenetic Protein was implanted in 30 consecutive femoral reconstructions that resulted from failure of fracture healing. There were 24 atrophic shortened femoral nonunions, four equal length femoral nonunions, and two femoral malunions. There were 10 men and 20 women with an average age of 47 years (range, 28-75 years). Allogeneic, autolysed antigen-free cortical Bone was used as a structural alloimplant and as a delivery system for partially purified human Bone Morphogenetic Protein. The composite implant of human Bone Morphogenetic Protein/allogeneic, autolysed antigen-free cortical Bone was used in conjunction with one-stage lengthening of the extremity, restoration of mechanical axis and rotational alignment. In 26 of 30 femurs, the human Bone Morphogenetic Protein/allogeneic autolysed antigen-free cortical Bone consisted of an allogeneic cortical Bone implant incorporated into a one-stage lengthening of atrophic femoral nonunion. In four patients with equal length femoral nonunions, the human Bone Morphogenetic Protein/allogeneic, autolysed antigen-free implant was placed as an medical femoral shaft onlay graft. Internal remodeling of the implant occurred within 8 to 12 weeks after implantation. Lengthening defects greater than 2 cm were supplemented with intercalary autogeneic Bone graft. Twenty-four femurs healed at an average of 6 months at an average followup of 55 months. Four of six plate fatigue failures were salvaged with repeat plating. Two patients were lost to followup. The human Bone Morphogenetic Protein/allogeneic, autolysed antigen-free Bone allograft is an excellent structural and delivery system that induces host Bone formation and implant remodeling allowing salvage of difficult femoral nonunions.

  • Bone Morphogenetic Protein excipients: comparative observations on poloxamer.
    Plastic & Reconstructive Surgery, 2000
    Co-Authors: Cameron M. L. Clokie, Marshall R. Urist
    Abstract:

    Clinicians await the availability of synthetic bioimplants that will replace the need for autogeneic Bone grafts in Bone reconstructive surgery. For more than a decade, researchers have evaluated delivery vehicles for the tissue morphogen Bone Morphogenetic Protein. The object of this investigation was to measure induced Bone development when Bone Morphogenetic Protein was delivered by human tendon collagen, human demineralized Bone matrix, hydroxyapatite, a composite of human tendon collagen and human demineralized Bone matrix (tendon collagen + demineralized Bone matrix), Poloxamer 407, and a composite of human demineralized Bone matrix and Poloxamer 407. Sixty-three adult male Swiss Webster mice (Harlan Sprague-Dawley, Indianapolis, Ind.) received 126 implants. The animals were divided into seven groups of nine animals, depending on carrier (six carriers plus the positive control group) used. Each animal received a Bone Morphogenetic Protein-enhanced carrier in one hindquarter muscle mass, with the contralateral leg being implanted with the carrier alone. Implants were evaluated by quantitative radiomorphometry validated by histologic methods. Radiographically, no significant differences were identified among any of the implants evaluated (p > 0.05). Histomorphometric analysis demonstrated that Poloxamer 407 was significantly (p < 0.05) better at delivering Bone Morphogenetic Protein than the other carriers involved in this investigation. The new Bone developed in a tubular or spherical shape. Interaction of endogenous and exogenous delivery systems seems to be essential for optimal transmission of Bone Morphogenetic Protein. The importance of the excipient to deliver Bone Morphogenetic Protein and develop a Bone Morphogenetic Protein concentration gradient has been emphasized by other investigators and confirmed by our research on poloxamer. With further research on the physicochemical mechanisms of localization and transmission of Bone Morphogenetic Protein, it may be possible to avoid hazardous operations with autogeneic Bone.

  • One-stage Lengthening of Femoral Nonunion Augmented With Human Bone Morphogenetic Protein
    Clinical Orthopaedics and Related Research, 1998
    Co-Authors: Eric E. Johnson, Marshall R. Urist
    Abstract:

    Fifteen patients with posttraumatic shortened atrophic femoral nonunions were treated with one-stage lengthening. The alloimplant was composed of allogeneic antigen extracted autolyzed human Bone perfused with partially purified human cortical Bone Morphogenetic Protein associated with noncollagenous Protein and used as graft. The composite was lyophilized and sterilized with ethylene oxide. All 15 nonunions were atrophic diaphyseal and were lengthened through intercalary segmental defects bridged with the human Bone Morphogenetic Protein composite alloimplants stabilized to the medial femoral cortex through plate osteosynthesis and lag screw fixation. One lengthened proximal femur had fatigue failure of the plate and was treated successfully by exchange plating. The average increase in length was 2.8 cm (range, 1.5-5 cm) and an average percentage increase in length of 8% (range, 4%-132%) of the residual shortened femur. The human Bone Morphogenetic Protein composite produced an immediate reactive Bone formation in the host Bone and progressive remodeling of the donor recipient interfaces. There were no infections, allergic reactions, clinical rejection of the human Bone Morphogenetic Protein composite alloimplants, or evidence of malignant disease. One-stage femoral lengthening augmented with human Bone Morphogenetic Protein composite graft bridged the intercalary defect, remodeled the atrophic host Bone and restored Bone continuity within 1 to 2 years. Human Bone Morphogenetic Protein composite alloimplants are a substitute of autogeneic Bone graft and offer an alternative to iliac crest Bone without the associated morbidity.

Haramol Singh Sandhu - One of the best experts on this subject based on the ideXlab platform.

  • experimental spinal fusion with recombinant human Bone Morphogenetic Protein 2 without decortication of osseous elements
    Spine, 1997
    Co-Authors: Haramol Singh Sandhu, Linda E A Kanim, J. Michael Kabo, J. M. Toth, Rick B. Delamarter, Edgar G. Dawson
    Abstract:

    STUDY DESIGN: L4-L5 intertransverse process fusions were produced with 58 micrograms, 230 micrograms, or 920 micrograms of recombinant human Bone Morphogenetic Protein-2 in 20 dogs. Eleven had traditional decortication of posterior elements before insertion of the implant. Nine were left undecorticated. All animals were evaluated 3 months after surgery. OBJECTIVES: To determine whether decortication is a prerequisite for successful fusion in the presence of osteoinductive Proteins such as Bone Morphogenetic Protein-2. SUMMARY OF BACKGROUND DATA: Recombinant osteoinductive Proteins can induce de novo Bone in ectopic soft-tissue sites in the absence of Bone marrow elements. Traditional methods for achieving spinal fusion rely on exposure of Bone marrow through decortication to facilitate osteogenesis. It is hypothesized that the presence of an implanted osteoinductive Protein obviates the need for exposure and release of host inductive factors. METHODS: Recombinant human Bone Morphogenetic Protein-2-induced intertransverse process fusions were performed with and without decortication. Fusion sites were evaluated by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis. RESULTS: One hundred percent of decorticated spines and 89% of undecorticated spines were clinically fused by 3 months. Ninety-one percent of decorticated spines and 78% of undecorticated specimens exhibited bilateral transverse process osseous bridging. The only spines that failed to achieve solid bilateral arthrodesis were in the lowest dose group. With the higher two doses, there was histologic evidence of osseous continuity between the fusion mass and undecorticated transverse processes. CONCLUSIONS: There were no statistical differences in clinical and radiographic fusion rates between decorticated and undecorticated sites. With higher doses of recombinant human Bone morphoganetic Protein-2, there was little histologic distinction between fusions in decorticated versus undecorticated spines.

  • Effective doses of recombinant human Bone Morphogenetic Protein-2 in experimental spinal fusion
    Spine, 1996
    Co-Authors: Haramol Singh Sandhu, Erik N Zeegen, Linda E A Kanim, J. Michael Kabo, J. M. Toth, Rick B. Delamarter, D. Liu, Edgar G. Dawson
    Abstract:

    STUDY DESIGN: Nineteen dogs underwent L4-L5 intertransverse process fusions with either 58 micrograms, 115 micrograms, 230 micrograms, 460 micrograms, or 920 micrograms of recombinant human Bone Morphogenetic Protein-2 carried by a polylactic acid polymer. A previous study (12 dogs) compared 2300 micrograms of recombinant human Bone Morphogenetic Protein-2, autogenous iliac Bone, and carrier alone in this model. All fusions subsequently were compared. OBJECTIVES: To characterize the dose-response relationship of recombinant human Bone Morphogenetic Protein-2 in a spinal fusion model. SUMMARY OF BACKGROUND DATA: Recombinant osteoinductive morphogens, such as recombinant human Bone Morphogenetic Protein-2, are effective in vertebrate diaphyseal defect and spinal fusion models. It is hypothesized that the quality of spinal fusion produced with recombinant human Bone Morphogenetic Protein-2, above a threshold dose, does not change with increasing amounts of inductive Protein. METHODS: After decortication of the posterior elements, the designated implants were placed along the intertransverse process space bilaterally. The fusion sites were evaluated after 3 months by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis. RESULTS: As in the study using 2300 micrograms of recombinant human Bone Morphogenetic Protein-2, implantation of 58-920 micrograms of recombinant human Bone Morphogenetic Protein-2 successfully resulted in intertransverse process fusion in the dog by 3 months. This had not occurred in animals containing autograft or carrier alone. The cross-sectional area of the fusion mass and mechanical stiffness of the L4-L5 intersegment were not dose-dependent. Histologic findings varied but were not related to rhBMP-2 dose. Inflammatory reaction to the composite implant was proportional inversely to the volume of the fusion mass. CONCLUSIONS: No mechanical, radiographic, or histologic differences in the quality of intertransverse process fusion resulted from a 40-fold variation in dose of recombinant human Bone Morphogenetic Protein-2.

Russell F Warren - One of the best experts on this subject based on the ideXlab platform.

  • use of recombinant human Bone Morphogenetic Protein 2 to enhance tendon healing in a Bone tunnel
    American Journal of Sports Medicine, 1999
    Co-Authors: Scott A Rodeo, John M. Wozney, Katsunori Suzuki, Xianghua Deng, Russell F Warren
    Abstract:

    This study examines the hypothesis that recombinant human Bone Morphogenetic Protein-2 can enhance Bone ingrowth into a tendon graft placed into a Bone tunnel. We transplanted the long digital extensor tendon into a drill hole in the proximal tibia in 65 adult mongrel dogs. We applied two different doses of the Bone Morphogenetic Protein to the tendon-Bone interface in one limb using an absorbable type I collagen sponge carrier and only the collagen sponge to the contralateral (control) limb. The healed tendon-Bone attachment was evaluated at serial times between 3 days and 8 weeks using radiography, histologic examination, and biomechanical testing. At all time points, histologic and radiographic examination demonstrated more extensive Bone formation around the tendon with closer apposition of new Bone to the tendon in the Protein-treated limb than in the paired control limb. Biomechanical testing demonstrated higher tendon pull-out strength in the Protein-treated side at all time points, with a statistically significant difference between the low-dose-treated side and the control side at 2 weeks. The histologic and biomechanical data suggested superior healing at the lower Protein dose. This study demonstrated that Bone Morphogenetic Protein can accelerate the healing process when a tendon graft is transplanted into a Bone tunnel.

Randy Rosier - One of the best experts on this subject based on the ideXlab platform.

  • How does recombinant human Bone Morphogenetic Protein-4 enhance posterior spinal fusion?
    Spine, 2002
    Co-Authors: Jack C. Y. Cheng, Lai Pang Law, Kwong Man Lee, Daniel H K Chow, Xia Guo, Randy Rosier
    Abstract:

    STUDY DESIGN: A rabbit posterolateral intertransverse process fusion model was used to evaluate the effect that different doses of recombinant human Bone Morphogenetic Protein-4 delivered in a porous hydroxyapatite-tricalcium phosphate ceramic had on osteogenesis and spinal fusion.\n\nOBJECTIVE: To study the biologic effect and threshold dose of recombinant human Bone Morphogenetic Protein-4 in enhancing spinal fusion.\n\nSUMMARY OF BACKGROUND DATA: Biologic manipulation for spinal fusion is an area undergoing active research. The enhancing effects of recombinant human Bone Morphogenetic Proteins 2 and 7 on spinal fusion have been proved, and clinical trials of their application are in progress. Recombinant human Bone Morphogenetic Protein-4 is another osteoinductive Protein that has the ability to induce heterotopic Bone formation, and its potential for enhancing spinal fusion has not yet been studied.\n\nMETHODS: For this study, 24 adult New Zealand white rabbits underwent single-level unilateral posterior intertransverse process spinal fusion at L5-L6. The animals were divided into four groups using different graft materials: allograft as well as hydroxyapatite-tricalcium phosphate augmented with 0, 1.25, and 5 microgram of recombinant human Bone Morphogenetic Protein-4, respectively. The local changes were evaluated by sequential radiograph, manual palpation, histomorphology, and microradiography.\n\nRESULTS: At week 7, ossification in the intertransverse process area ceased in groups without recombinant human Bone Morphogenetic Protein-4, whereas active multicentric endochondral Bone formation was demonstrated in groups with this growth factor. The success rate of contiguous bony bridging was found to correlate positively with the dose of recombinant human Bone Morphogenetic Protein-4.\n\nCONCLUSIONS: Recombinant human Bone Morphogenetic Protein-4 effectively enhances new Bone formation and accelerates fusion in the rabbit posterolateral posterior spinal fusion model. The effective dose of recombinant human Bone Morphogenetic Protein-4 is 10 times lower than the reported dosage of recombinant human Bone Morphogenetic Proteins 2 and 7.