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Biomedical subjects

S D Boden

Publications and source records attributed to S D Boden.

At least 37 records · Page 2Linked to original sources
PubMed1999

Posterolateral lumbar intertransverse process spine arthrodesis with recombinant human bone morphogenetic protein 2/hydroxyapatite-tricalcium phosphate after laminectomy in the nonhuman primate.

STUDY DESIGN: A nonhuman primate lumbar intertransverse process arthrodesis model was used to evaluate recombinant human bone morphogenetic protein 2 (rhBMP-2) in a hydroxyapatite-tricalcium phosphate (HA-TCP) carrier as a complete bone graft substitute. OBJECTIVES: To assess the ability of a ceramic material to serve as a carrier for various doses of rhBMP-2 as a bone graft substitute in a primate model of posterolateral intertransverse process spinal fusion after laminectomy. SUMMARY OF BACKGROUND DATA: The reported non-union rates for posterolateral lumbar spine fusion with autogenous iliac crest bone range from 5-35%. Recombinant human bone morphogenetic protein 2 has shown potential to serve as a bone graft substitute for posterolateral intertransverse process spine fusion. Although a resorbable collagen sponge was a suitable carrier in rabbits and dogs, it was too compressible for the paraspinal muscles in rhesus monkeys. This failure of the collagen carrier has prompted evaluation of the feasibility of an alternative carrier material and the required dose of rhBMP-2. METHODS: Twenty-one adult rhesus monkeys underwent a laminectomy at L4-L5 followed by bilateral intertransverse process arthrodesis via the same midline incision (n = 16) or a minimally invasive video-assisted posterolateral approach (n = 5). Bone graft implants on each side consisted of either 5 cm3 of autogenous iliac crest bone or 60:40 HA-TCP blocks (1.2 x 0.5 x 3.7 cm) loaded with a solution containing 0, 6, 9, or 12 mg of rhBMP-2 per side. The monkeys were killed 24 weeks after surgery. Inspection, manual palpation, radiography, and histology were used to assess fusion and to detect any bony growth into the laminectomy defect. RESULTS: Fusion was not achieved in any of the monkeys treated with autogenous iliac crest bone graft. Both of the monkeys treated with the HA-TCP blocks with 0 mg rhBMP-2 achieved fusion. All 15 monkeys treated with the HA-TCP blocks and either of the three doses of rhBMP-2 achieved solid fusion. Two animals had extension of the fusion on one side because of malpositioned ceramic block. The results in animals fused via the minimally invasive video-assisted technique were the same as inthose fused with the open technique. Histologic analysis showed some ingrowth of bone into the ends but not-through the ceramic block in the absence of rhBMP-2. When the ceramic blocks were loaded with rhBMP-2 there was a dose-dependent increase in the amount and quality of bone throughout the ceramic carrier based on qualitative assessment. No significant bone encroachment on the exposed thecal sac through the laminectomy defect was observed in any of the monkeys. CONCLUSION: Hydroxyapatite-tricalcium phosphate proved to be a suitable carrier for rhBMP-2 in the posterolateral spine fusion model in rhesus monkeys. Even in the presence of a laminectomy defect, there was no evidence of bone induction outside the confines of the ceramic carrier.

Animals↗
PubMed1999

New formulations of demineralized bone matrix as a more effective graft alternative in experimental posterolateral lumbar spine arthrodesis.

STUDY DESIGN: A rabbit model of posterolateral intertransverse process spine arthrodesis was used. OBJECTIVE: To determine the efficacy of two new formulations of demineralized bone matrix. SUMMARY OF BACKGROUND DATA: The flowable gel form of Grafton (Osteotech, Eatontown, NJ) demineralized bone matrix has been shown to have osteoinductive properties in various models and currently is used clinically as bone graft material in posterolateral lumbar spine arthrodesis. Two new formulations of Grafton, one made of flexible sheets (Flex) and the other made in a malleable consistency (Putty), have improved handling characteristics compared with the gel form. METHODS: In this study, 108 New Zealand white rabbits underwent bilateral posterolateral intertransverse spine arthrodesis at L5-L6 using autogenous iliac crest bone graft alone (control), one of the new forms of demineralized bone matrix (DBM; made from rabbit bone) alone or in combination with autogenous iliac crest bone. Rabbits were killed 6 weeks after surgery. The lumbar spines were excised, and fusion success or failure was determined by manual palpation and radiography. Specimens also were processed for undecalcified histologic analysis. RESULTS: Manual palpation of the harvested lumbar spines revealed that the fusion rates of the Flex-DBM/Auto group (9/9, 100%) and Putty-DBM/Auto group (10/10, 100%) were superior (P < 0.01) to those of the Auto/control group (3/9, 33%). As a stand-alone graft substitute, Flex-DBM performed superiorly with a fusion rate of 11/11 (100%) compared with that of Putty-DBM (10/12, 83%) and Gel-DBM (7/12, 58%). The devitalized version of Flex-DBM had a fusion rate of 4/11 (36%), which was comparable with the devitalized Putty-DBM rate of 4/12 (33%). Both were superior (P < 0.05) to the devitalized Gel-DBM rate of 0/12 (0%). More mature fusions with greater amounts of trabecular bone were present radiographically and histologically in rabbits that received all forms of demineralized bone matrix than in those in which autograft was used. CONCLUSIONS: The new flexible sheet and malleable putty forms of demineralized bone matrix were effective as graft extender and graft enhancer in a model of posterolateral lumbar spine fusion. These newer formulations of Grafton appear to have a greater capacity to form bone than the gel form or autogenous bone graft alone in this model.

Animals↗
PubMed1999

Molecular biology and spinal disorders. A survey for the clinician.

Over the past 10 years, advances in molecular biology techniques have extended the potential for understanding spinal disorders from the microscopic (histologic) level down to the molecular level of gene expression within individual cells. These advances are initiating new avenues of research and, ultimately, novel clinical treatments. The intent of this update is to provide the spine clinician with a basic understanding of molecular biology, the type of information that may be learned from its application, and the potential for gene therapy in spine disorders.

DNA↗
PubMed1999

The use of coralline hydroxyapatite with bone marrow, autogenous bone graft, or osteoinductive bone protein extract for posterolateral lumbar spine fusion.

STUDY DESIGN: A posterolateral lumbar arthrodesis animal model using coralline hydroxyapatite as a bone graft substitute. OBJECTIVE: To determine the effectiveness of coralline hydroxyapatite as a bone graft substitute for lumbar spine fusion when used with bone marrow, autogenous bone graft, or an osteoinductive bone protein extract. SUMMARY OF BACKGROUND DATA: Coralline hydroxyapatite is commonly used as a bone graft substitute in metaphysial defects but its use in a more challenging healing environment such as the posterolateral spine remains controversial. There are no published animal studies in which the use of coralline hydroxyapatite has been evaluated in a posterolateral lumbar arthrodesis model. METHODS: Single-level posterolateral lumbar arthrodesis was performed at L5-L6 in 48 adult New Zealand White rabbits. Rabbits were assigned to one of three groups based on the graft material they received: 3.0 mL coralline hydroxyapatite 1.5 mL plus bone marrow; 1.5 mL coralline hydroxyapatite plus 1.5 mL autogenous iliac crest bone; and, 3.0 mL coralline hydroxyapatite plus 500 micrograms bovine-derived osteoinductive bone protein extract on each side. Rabbits were killed after 2, 5, or 10 weeks, and the spines were excised and evaluated by manual palpation, radiographs, tensile biomechanical testing, and nondecalcified histology. RESULTS: Fusions were assessed by manual palpation at 5 weeks for comparisons among the three groups of graft materials. The coralline hydroxyapatite used with bone marrow produced no solid fusions (0/14). When combined with an equal amount of autogenous iliac crest bone, coralline hydroxyapatite resulted in solid fusion in 50% (7/14) of the rabbits (P < 0.05). When combined with the osteoinductive growth factor extract, the coralline hydroxyapatite resulted in solid fusion in 100% (11/11) of the rabbits (P < 0.05). The fusion masses in the growth factor group were significantly stronger (1.8 +/- 0.2 vs. 1.3 +/- 0.1; P = 0.02) and stiffer (1.5 +/- 0.2 vs. 1.2 +/- 0.1, P = 0.04) based on tensile testing to failure when normalized to the adjacent unfused level. CONCLUSION: These data indicate that coralline hydroxyapatite with bone marrow was not an acceptable bone graft substitute for posterolateral spine fusion. When combined with autogenous iliac crest bone graft-coralline hydroxyapatite served as a graft extender yielding results comparable to those obtained with autograft alone. Coralline hydroxyapatite served as an excellent carrier for the bovine osteoinductive bone protein extract yielding superior results to those obtained with autograft or bone marrow.

Animals↗
PubMed1999

Osteoinductive bone graft substitutes for spinal fusion: a basic science summary.

An understanding of precise biologic mechanisms at work during spinal fusion healing is just beginning to evolve. Current molecular biology research has shown this process to be multifactorial and extremely complex. With the advent of improved animal models to study the biology of spinal fusion, essential information regarding the basic science behind arthrodesis has advanced knowledge of this process. Moreover, with advances in local gene therapy as well as osteoinductive proteins and osteoinductive carrier matrices, the orthopedic surgeon will soon enter into a new era of biologic manipulation for fusion.

Animals↗
PubMed1999

Natural history of rheumatoid arthritis of the cervical spine.

This article reviews the natural history of rheumatoid arthritis involving the cervical spine with special attention given to predictors of paralysis. Understanding the natural history of rheumatoid arthritis of the cervical spine is necessary to determine the benefit of various interventions. The primary treatment goal for cervical instability is prevention of irreversible neurologic injury. The natural history of rheumatoid arthritis for a period of 10 years or more is one of significant disease progression. The natural history of cervical instability in patients with rheumatoid arthritis is more variable, with only some patients having a neurologic deficit develop. Recent studies support prophylactic stabilization of the rheumatoid cervical spine to prevent paralysis in high risk patients. However, proponents for prophylactic arthrodesis must acknowledge that not all cervical instability in rheumatoid arthritis progresses to neurologic deficit, and surgical intervention in patients with rheumatoid arthritis incurs added morbidity and mortality. Identifying the risk factors for progression of cervical instability is the first step in eliminating morbidity and mortality from spinal cord and brain stem compression. Surgical stabilization is indicated not only for those patients with paralysis, but for the subgroups of patients with cervical rheumatoid disease who are at risk for spinal cord and brain stem compression. The posterior atlantodental interval is the most reliable screening tool and predictor of progressive neurologic deficit.

Arthritis, Rheumatoid↗
PubMed1999

Bioactive factors for bone tissue engineering.

Orthopaedic surgery is currently in the midst of a transformation from bone grafting and the use of bone graft substitutes to bone tissue engineering. Bioactive bone growth factors likely will play a particularly important role in this emerging field. This article will review the three leading strategies for using bioactive factors for bone tissue engineering: extraction and partial purification of growth factors, recombinant protein synthesis, and gene therapy. Preclinical and early clinical trial results with bone morphogenetic protein-2, bone morphogenetic protein-7 (osteogenic protein-1), and NeOsteo bovine bone protein extract will be reviewed. In addition, the current obstacles to clinical implementation of bone tissue engineering will be reviewed.

Animals↗
PubMed1999

Graft healing in laryngotracheal reconstruction: an experimental rabbit model.

The actual sequence of events in graft healing in laryngotracheal reconstruction (LTR) is not well understood. To investigate sequential changes in graft healing, we submitted 21 rabbits to LTR with an anterior auricular cartilage graft. They were immediately extubated after surgery, and no stent was used. Rabbits were painlessly sacrificed at 7 different time periods (0, 1, 2, 3, 4, 6, and 10 weeks after surgery). Cross sections of the larynx and graft were cut and stained with hematoxylin-eosin and trichrome. Epithelialization progressed very rapidly and was complete by 21 days. During the 10 weeks, there was a progressive necrosis and resorption of the original graft cartilage. However, neochondrification progressed very rapidly and resulted in excellent structural support of the graft in the airway. Problems, such as infection and granulation tissue formation, were relatively minor and infrequent.

Animals↗
PubMed1999

Posterolateral intertransverse process spinal arthrodesis with rhBMP-2 in a nonhuman primate: important lessons learned regarding dose, carrier, and safety.

Recombinant osteoinductive proteins have been used successfully in canine and rabbit models of posterolateral intertransverse process arthrodesis, but little is known about the ability of these compounds to achieve fusion in nonhuman primates. The goals of this investigation were to compare different combinations of recombinant human bone morphogenetic protein-2 (rhBMP-2) dosages and carriers in a nonhuman primate model of posterolateral intertransverse process spinal fusion and to determine the feasibility of using rhBMP-2 in the presence of exposed dura in a laminectomy model. Posterolateral intertransverse process arthrodeses were performed at L4-5 in 29 rhesus monkeys. The most striking findings were as follows: rhBMP-2 could induce bone in a nonhuman primate spine; the presence of a laminectomy defect with exposed dura did not preclude the safe use of rhBMP-2 for posterolateral fusion; soft tissue compression of the collagen sponge carrier prevented bone induction at standard BMP doses, presumably due to squeezing of the protein out of the sponge; and longer rhBMP-2 loading time into the collagen carrier and mechanical protection from the soft tissue compression both allowed more bone induction at a lower dose of rhBMP-2.

Animals↗
PubMed1998

Inflammatory disorders of the cervical spine.

The most common inflammatory disorders affecting the cervical spine include adult and juvenile rheumatoid arthritis, ankylosing spondylitis, Reiter's syndrome, and psoriatic arthritis. These disorders are characterized by typical deformities and instabilities of the cervical spine that result from the destruction caused by synovitis in bony and ligamentous structures in the neck. The treatment of these inflammatory lesions differs from the treatment of similar lesions found in the posttraumatic or degenerative spine. This article attempts to outline the epidemiology, clinical manifestations, and natural history of these conditions. Various radiographic parameters for evaluating disease progression have been used over the years, and their usefulness is reviewed in the context of recent studies better defining the radiographic natural history of these lesions. An algorithm for the use of the various imaging methods including magnetic resonance scanning is provided, and recent progress in delineating the proper timing of surgical intervention and the predictors of neurologic recovery is presented. The current surgical procedures available to treat these conditions are discussed with emphasis on distinguishing those cases in which stabilization alone is required from those in which a decompression procedure is also necessary.

Adult↗
PubMed1998

Lumbar spine fusion by local gene therapy with a cDNA encoding a novel osteoinductive protein (LMP-1).

STUDY DESIGN: A posterior arthrodesis animal model using local expression of a newly discovered osteoinductive protein delivered in bone marrow cells. OBJECTIVE: To introduce the concept of local gene therapy and determine its feasibility for achieving lumbar spine fusion using a gene for a novel osteoinductive protein: LIM Mineralization Protein-1 (LMP-1). SUMMARY OF BACKGROUND DATA: Extensive work is currently underway to improve the healing success and morbidity associated with the gold standard bone-grafting material of autogenous iliac crest. As a result, alternative osteoinductive proteins and new delivery methods warrant investigation. The authors' laboratory recently identified a novel gene that had osteoinductive capacity in vitro and is therefore a candidate for a new in vivo osteoinductive agent. METHODS: Single-level posterior lumbar and thoracic arthrodesis was attempted in 14 athymic rats. The graft material, which consisted of a devitalized bone matrix (no osteoinductive activity) soaked with 0.75 to 1.5 million bone marrow cells, was inserted with the dorsal spine exposed. In each rat, one site received marrow cells transfected with the cDNA encoding a novel osteoinductive protein. At the other site for a control, the marrow cells were transfected with the reverse copy of the cDNA that did not express any protein. Transfection of marrow cells for 2 hours was accomplished using the mammalian expression vector pCMV2. Rats were killed after 4 weeks, and the spines were evaluated by manual palpation, radiographs, and nondecalcified histology. RESULTS: In the pivotal experiment, successful spine fusion was obtained in 9/9 (100%) of the sites receiving marrow cells transfected with the active LMP-1 cDNA and in 0/9 (0%) of the sites receiving marrow cells transfected with the reverse (inactive) LMP-1 cDNA. Radiographs and histology confirmed the manual palpation results, demonstrating controlled new bone formation in the carrier and marrow transfected with the active LMP-1 cDNA and essentially no bone induction in the sites treated with marrow cells that did not express the protein. CONCLUSIONS: These data confirm that local delivery of the novel LMP-1 cDNA using bone marrow cells is feasible in vivo. Furthermore, these results demonstrate that posterior thoracic or lumbar spine fusion can be achieved in rats by local delivery of the LMP-1 cDNA.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Vascularization of the fusion mass in a posterolateral intertransverse process fusion.

STUDY DESIGN: A previously characterized rabbit model was used to study vascularization of the fusion mass in a posterolateral intertransverse process fusion. OBJECTIVES: To determine the interosseus origin of the new blood vessels in a posterolateral intertransverse process fusion mass and to test the hypothesis that bone incorporation and the extent of vascularization are closely related. SUMMARY OF BACKGROUND DATA: It has been reported that vascularization is essential for bone graft incorporation. There are, however, few reports dealing with vascularization of the spinal arthrodesis. METHODS: Thirty-one adult New Zealand White rabbits underwent bilateral intertransverse process fusion, using autogenous iliac crest bone graft. The rabbits were killed at 3 weeks (n = 6) and 6 weeks (n = 25) after surgery, and colored silicone was injected to fix the vasculature. A semiautomated image analysis system was used to assess the percentage of the area of vascularization in the fusion mass and the transverse processes. RESULTS: The major interosseus blood supply for vascularization of the autogenous bone graft came from upper and lower transverse processes. There were three types of fusion mass observed at 6 weeks after surgery: solid type, solid type with cartilaginous cleft, and nonunion type. There was significantly less vascularization of the fusion mass and of the transverse processes in the nonunion type compared with that in the solid type and with that in the cartilaginous cleft type. CONCLUSIONS: There is a close correlation between bone incorporation and the extent of vascularization in a posterolateral intertransverse process fusion.

Angiography↗
PubMed1998

Reversing the inhibitory effect of nicotine on spinal fusion using an osteoinductive protein extract.

STUDY DESIGN: The effect on spinal fusion of an osteoinductive bone protein extract in the presence of a known inhibitor of spinal fusion (systemic nicotine) was studied prospectively in an animal model of posterolateral lumbar fusion. OBJECTIVES: To evaluate the ability of a bovine-derived osteoinductive bone protein extract to overcome the inhibitory effect of nicotine in a rabbit spine fusion model. SUMMARY OF BACKGROUND DATA: Multiple studies have demonstrated the ability of a variety of osteoinductive growth factors to serve as a bone graft substitute for lumbar spinal fusion under "normal" healing conditions. METHODS: Forty-eight adult female New Zealand white rabbits underwent spine arthrodesis at L5-L6 while receiving systemic nicotine through a subcutaneous miniosmotic pump. Arthrodesis was performed using one of the following three graft materials: 1) autogenous iliac crest, 2) osteoinductive bone protein delivered in an allogeneic demineralized bone matrix/ collagen carrier, or 3) osteoinductive bone protein delivered with autogenous iliac crest. Fusions were assessed by blinded manual palpation, radiography, and biomechanical testing. RESULTS: Of the 44 rabbits manually tested by blinded observers, all 14 in the osteoinductive bone protein plus autogenous iliac crest bone group had solid fusions (14 of 14), whereas the fusion rate was less in the osteoinductive bone protein plus demineralized bone matrix group (nine of 14, 64%; P = 0.02), and there were no fusions in the autogenous iliac crest only group (0 of 16, 0%; P = 0.000001). The use of osteoinductive bone protein with autogenous bone produced stronger and stiffer fusions compared with those using autogenous bone alone or osteoinductive bone protein with allograft bone. CONCLUSIONS: Cigarette smoking and nicotine are inhibitory factors in the healing of fractures and spine fusions. This study shows that the inhibitory effect of nicotine can be overcome with an osteoinductive bone growth factor in an animal model.

Animals↗
PubMed1998

Experimental posterolateral lumbar spinal fusion with a demineralized bone matrix gel.

STUDY DESIGN: A controlled rabbit model of lumbar posterolateral intertransverse process arthrodesis was used to evaluate a bone graft substitute. OBJECTIVE: To determine the efficacy of demineralized bone matrix gel as an autograft extender, using different ratios of demineralized bone matrix to autograft and to determine the efficacy of demineralized bone matrix as an autogenous bone graft enhancer by adding it to the usual quantity of autograft. SUMMARY OF BACKGROUND DATA: Autogenous bone is considered the most effective bone graft material for posterolateral lumbar arthrodesis, yet nonunions occur in up to 30% of patients. In addition, donor site complications may occur in 25-30% of patients. This has prompted the search for and investigation of bone graft extenders, enhancers, and substitutes. Commercially available demineralized bone matrix gel is one possible graft extender and enhancer, which, unlike mineralized allografts, has osteoinductive properties. Although the gel is in common use, the efficacy of demineralized bone matrix when used for posterolateral spine arthrodesis has not been examined in prospective clinical studies. Furthermore, no known animal studies have tested demineralized bone matrix gel in a posterolateral arthrodesis model. METHODS: Forty-seven New Zealand white rabbits underwent bilateral posterolateral spine arthrodesis at L5-L6 using autogenous iliac crest bone graft alone or in combination with demineralized bone matrix. Four groups were formed on the basis of the ratio of autograft to demineralized bone matrix: autograft alone (3 mL), 100:0 group; autograft (3 mL) and demineralized bone matrix (1.5 mL), 100:50 group; autograft (1.5 mL) and demineralized bone matrix (1.5 mL), 50:50 group; and autograft (0.75 mL) and demineralized bone matrix (2.25 mL), 25:75 group. Rabbits were killed 6 weeks after surgery. Inspection, manual palpation, radiographic film, and histologic evaluation were used to assess fusion. RESULTS: All groups had similar fusion rates (66-73%) based on manual palpation. Rabbits implanted with demineralized bone matrix had more mature fusion masses, evidenced by the greater trabecular bone formation seen on radiographic film and histologic study. CONCLUSIONS: Demineralized bone matrix was effective as a graft extender when used in up to a 3:1 ratio with autograft in a rabbit posterolateral spine fusion model. When less than the standard volume of autograft was used, the addition of demineralized bone matrix gel lead to fusion success rates comparable to those of the standard amount of autograft alone. However, demineralized bone matrix did not increase the frequency of successful fusion when added to the standard amount of autograft.

Animals↗
PubMed1998

The biology of posterolateral lumbar spinal fusion.

This article reviews the existing knowledge base concerning the biology of spinal fusion, with the understanding that the focus is weighted toward posterolateral lumbar spinal fusion because of a relative paucity of biologic information on healing of other types of fusions. The discussion focuses first on the basic science of spinal fusion healing from the standpoint of animal modeling. Next, the discussion centers on the multitude of local factors that can affect fusion healing. Finally, the numerous systemic factors known to affect fusion healing are discussed.

Animals↗
PubMed1998

Biologic enhancement of spinal fusion.

Scientific advances in the past decade have generated considerable clinical interest in developing biologic tools that may ultimately enhance spinal fusion. This article reviews the current understanding of each of these and other fusion-enhancing tools with particular attention to the results of in vivo animal experimentation and, where available, objective clinical data.

Bone Matrix↗
PubMed1998

Outcome assessment after spinal fusion: why and how?

Outcomes of medical interventions today must reflect a more complete array of measurements, including health status, patient satisfaction, medical costs, and quality of life. This article discusses the rationale and methodology involved with measurement of health status, particularly as it applies to spinal disorders and spinal fusion. Generic and disease-specific instruments are reviewed, and their limitations are also discussed.

Health Status Indicators↗