- Email: [email protected]
Peptide Amphiphiles Serve as Improved Delivery Vehicles for rhBMP-2 in a Rabbit Spine Fusion Model
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NASS 32nd Annual Meeting Proceedings / The Spine Journal 17 (2017) S89–S110
nificantly more bone through growth by microCT compared to PEEK with average bone coverage scores of 1.62±0.89 and 0.43±0.51 respectively at 4 weeks (p<.01) and 1.79±1.19 and 0.69±0.87 respectively at 8 weeks (p<.05). The radiographic appearance of the bone growing through apertures with titanium was more robust and more mature than PEEK at all time points. Furthermore, bone grew more quickly in the group with a titanium surface as evidenced by higher bone formation at 4 weeks compared to the PEEK group at 8 weeks. Histology corroborated these findings by demonstrating new bone formation in direct apposition to titanium surfaces both inside the apertures and on the implant surface. CONCLUSIONS: A commercially pure titanium surface on PEEK resulted in higher quantity and faster rate of bone growth compared to identical unmodified PEEK implants in this sheep study. FDA DEVICE/DRUG STATUS: N/A, (510k Cleared Devices) (Approved for this indication).
median fusion score for the Vitrium group also increased significantly in Area B. Mean % bone increased significantly for both groups with time as residual implant reduced for the Vitrium group. Mean % bone was significantly higher for Vitrium at 26 weeks. While Vitrium was associated with a macrophage and GC response (significantly higher than PEEK at 8 weeks), scores reduced between 8 and 26 weeks (significantly for macrophages) to levels that were not significantly different to PEEK and therefore is not considered a safety issue. CONCLUSIONS: Vitrium, when filled with autograft, performed significantly better than PEEK filled with autograft at 26 weeks based on a significantly higher mean percent bone and the fact that at 26 weeks the radiographic and microscopic median fusion scores were high in the area initially occupied by Vitrium. FDA DEVICE/DRUG STATUS: Vitrium Cervical IBD (Not approved for this indication).
https://doi.org/10.1016/j.spinee.2017.07.144
https://doi.org/10.1016/j.spinee.2017.07.145
120. Vitrium Bioactive Glass Cervical Interbody Device Ovine Study Janet Krevolin, PhD1, Casey S. Lewis, MEng1, Peggy Lalor, PhD2, Howard B. Seim III, DVM3, Jeremiah T. Easley, DVM4; 1Bio2 Technologies, Woburn, MA, US; 2Histion, Everett, WA, US; 3Colorado State University, Fort Collins, CO, US; 4Preclinical Surgical Research Laboratory, Colorado State University, Fort Collins, CO, US
121. Peptide Amphiphiles Serve as Improved Delivery Vehicles for rhBMP-2 in a Rabbit Spine Fusion Model Gurmit Singh, BS1,2, Mark McClendon, PhD2,3, Sungsoo Seth Lee, PhD2,3,4, Karina Katchko, BS1,2, Andrew Schneider, MD, BA1,2, Joseph A. Weiner, BS1,2, Ralph W. Cook IV, BS1,2, Danielle S. Chun1,2, Michael S. Schallmo, BS1,2, Jonghwa Yun1, Anjan Ghosh1, Chawon Yun, PhD1,2, Soyeon Jeong1,2, Samuel I. Stupp, PhD2,3,4, Erin L. Hsu, PhD1,2, Wellington K. Hsu, MD1,2; 1Northwestern University, Department of Orthopaedic Surgery, Chicago, IL, US; 2Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, US; 3Department of Materials Science and Engineering, Northwestern University, Evanston, IL, US; 4Department of Biomedical Engineering, Northwestern University, Evanston, IL, US
BACKGROUND CONTEXT: Anterior cervical discectomy and fusion (ACDF) is an established treatment option for symptomatic degenerative disc disease. Current interbody materials used for ACDF are not resorbable, bioactive nor osteoconductive which result in clinical compromises. There are clear advantages of an osteoconductive, bioactive and resorbable implant: a) the ability to load shift from the implant to newly formed bone, b) avoidance of long-term stress shielding and c) elimination of imaging interference. PURPOSE: The purpose of this study was to evaluate implant resorption, fusion mass and tissue ingrowth into the resorbable Vitrium® bioactive glass interbody device and compare fusion performance to a PEEK control. STUDY DESIGN/SETTING: N/A. PATIENT SAMPLE: N/A. OUTCOME MEASURES: N/A. METHODS: Vitrium cervical IBDs were manufactured by mixing resorbable glass fibers with a binder, pore former and a liquid into a plastically moldable material and sintered to form a bioactive implant. The IBDs had an interconnected open pore network with a bulk porosity ranging from 35– 45% with both micro and macropores (100 µm-600 µm). Sheep underwent instrumented lumbar interbody fusion with autograft at L2-L3 and L4-L5 with a Vitrium or PEEK IBD. Specimens harvested at 0, 8 and 26 weeks were radiographed and embedded in methyl methacrylate. One ground section was taken from the lateral, central and medial aspects of each implant and stained with Stevenel’s blue/van Gieson stain. Fusion assessments were made semiquantitatively for two different areas: Area A (the areas available inside and outside the implants) and Area B (the area occupied by the resorbable implant) using radiographs and stained slides. Stained sections were evaluated quantitatively (histomorphometrically) for percent bone, percent residual implant material, percent residual graft, percent fibrous tissue, and percent chondral tissue. Necrosis and cellular parameters including lymphocytes, polymorphonuclear leukocytes, macrophages, giant cells (GCs), and plasma cells were also scored. RESULTS: Median radiograph fusion at 8 weeks was similar for both groups indicative of less than 10% connectivity between the vertebral bodies in Area A. The median score for fusion in Area A increased significantly between 8 weeks and 26 weeks for both groups with no significant difference at 26 weeks. For the Vitrium group there was radiographically evident connectivity achieved between vertebral bodies across Area B, with median scores increasing significantly between 8 weeks and 26 weeks to a connectivity level greater than 75%. Histology at 8 weeks showed that chondral tissue largely prevented fusion in both groups. Median fusion scores increased significantly for both groups between 8 and 26 weeks, the
BACKGROUND CONTEXT: Advances in biologics and other bone graft substitutes have decreased the rate of pseudarthrosis; however, there still exists a need for a product that elicits high fusion rates with minimal adverse effects. Recombinant human bone morphogenetic protein-2 (rhBMP-2) applied onto an absorbable collagen sponge (ACS) results in fusion rates of >90% in humans. However, the supraphysiologic dose of rhBMP-2 required with this vehicle can lead to serious complications. In previous work, we developed nanofiber scaffolds composed of peptide amphiphiles (PA) that are capable of delivering exogenous rhBMP-2. Additionally, we have further modified this PA to include an rhBMP-2 binding motif. PURPOSE: The purpose of this study was to evaluate the delivery of rhBMP-2 via non-binding PA or BMP-binding PA with the intent of reducing the amount of exogenous growth factor necessary to achieve bone regeneration and successful spine fusion in a rabbit posterolateral fusion (PLF) model. STUDY DESIGN/SETTING: N/A. PATIENT SAMPLE: N/A. OUTCOME MEASURES: N/A. METHODS: New Zealand white rabbits underwent bilateral PLF at L5L6 with either 30 µg or 60 µg of rhBMP-2 per animal (15 µg or 30 µg of rhBMP-2 per side) loaded onto BMP-binding PA with collagen, nonbinding PA with collagen, or collagen sponge. Spine fusion was assessed using radiographs, fusion scoring and microCT imaging. Fusion scores were determined by blinded manual palpation using an established scoring system: 0=no bridging bone, 1=unilateral bridging, and 2=bilateral bridging. Spines with an average score ≥1 were considered fused. New bone volume was assessed by microCT analysis. One-way ANOVA with Tukey’s post-hoc was used to evaluate for differences between groups with continuous variables. RESULTS: Rabbits treated with BMP-binding PA or non-binding PA loaded with 30 µg or 60 µg of rhBMP-2 (per animal) demonstrated significantly higher fusion scores by manual palpation than those treated with equivalently pre-loaded collagen sponge (2.0, 1.61 and 0.0, respectively, for 30 µg of rhBMP-2; 2.0, 2.0 and 1.04, respectively, for 60 µg of rhBMP-2; p<.05). Fusion scores between BMP-binding PA and non-binding PA preloaded with
NASS 32nd Annual Meeting Proceedings / The Spine Journal 17 (2017) S89–S110 equivalent doses of rhBMP-2 showed no significant difference. Furthermore, there was no significant difference between both doses of rhBMP-2 for binding PA or non-binding PA. BMP-binding PA loaded with 30 µg rhBMP-2 demonstrated significantly higher new bone volume than equally loaded collagen sponge as assessed by microCT (p<.05). There were no other significant differences in new bone volume as per microCT between the nonbinding PA group vs. collagen sponge group and the non-binding PA group vs. BMP-binding PA group all preloaded with 30 µg of rhBMP-2. CONCLUSIONS: Currently, ACS is the only approved carrier for rhBMP2. Our data suggests that both BMP-binding and non-binding PA are better carriers for rhBMP-2 compared to an equivalently loaded collagen sponge. Furthermore, these scaffolds can effectively reduce the dose requirement necessary for spinal fusion relative to collagen sponge alone. Although future studies will identify the lowest rhBMP-2 loading dose at which the BMPbinding or non-binding PA can promote fusion rates approaching 100%, our results indicate the BMP-binding PA is more promising. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. https://doi.org/10.1016/j.spinee.2017.07.146
122. Radiographic and CT Evaluation of Recombinant Human Bone Morphogenetic Protein-2-Assisted Cervical Spinal Interbody Fusion Luke J. Weisbrod1, John D. Leever, MD2, J. Kenneth Burkus, MD3, Kevin T. Foley, MD, FACS4, Randall F. Dryer, MD5, Paul M. Arnold, MD6; 1US; 2The University of Kansas Hospital, Kansas City, KS, US; 3The Hughston Clinic, PC, Columbus, GA, US; 4SemmesMurphey Clinic, Memphis, TN, US; 5Central Texas Spine Institute, L.L.P., Austin, TX, US; 6University of Kansas Medical Center/Department of Neurosurgery, Kansas City, KS, US BACKGROUND CONTEXT: N/A. PURPOSE: Studies investigating rhBMP-2 assisted spinal fusion have yielded promising results, suggesting rhBMP-2 as an efficacious alternative to iliac crest autografts. Spinal fusion assisted by rhBMP-2 both hastens healing and eliminates patient morbidity from iliac crest autograft. Unique to BMPassisted spinal fusion is its distinct radiographic fusion pattern as fusion is achieved. Despite promising results and increased clinical use of rhBMP2, there remains a paucity of literature documenting this radiographic process. The objective of this study is to radiographically demonstrate the distinct fusion pattern of rhBMP-2 in the setting of ACDF. STUDY DESIGN/SETTING: N/A. PATIENT SAMPLE: N/A. OUTCOME MEASURES: N/A. METHODS: This study included 26 patients who underwent single-level anterior cervical discectomy and fusion using rhBMP-2. RESULTS: A polyetheretherketone cage was used as an interbody disc spacer in all 26 patients. Patients were evaluated between 2 and 6 weeks after surgery and subsequently at 3,6,12 and 24 months post-op. All patients underwent plain radiography at every follow-up visit, and CT evaluation was performed at 3,6,12 and 24 months as part of the study protocol. CONCLUSIONS: rhBMP-2 leads to both successful interbody fusion and an enhanced fusion rate with unique imaging characteristics. Additional characteristics of BMP observed in 100% of patients included prevertebral soft-tissue swelling and early endplate resorption. Other common features included PEEK cage migration, heterotopic bone formation and subsidence of the cage. FDA DEVICE/DRUG STATUS: rhBMP-2 (Not approved for this indication). https://doi.org/10.1016/j.spinee.2017.07.147
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Research Grant Award Winner The Impact of Type 2 Diabetes on Bone Metabolism and Growth after Spinal Fusion Neil Bhamb, MD, Linda E.A. Kanim, MA, Ruben Maldonado, BS, Trevor Nelson, BS, Juliane Glaeser, PhD, Melodie F. Metzger, PhD BACKGROUND CONTEXT: Diabetes mellitus is a chronic metabolic disease with an enormous impact on public health. The incidence of type II diabetes (T2DM) has skyrocketed to epidemic proportions and is expected to rise. As the prevalence of diabetes continues to increase, so does the percentage of diabetics among patients undergoing spinal fusion surgery. Some clinical reports suggest diabetes may have a negative effect on spinal fusion outcomes, although no conclusive experimental research has been conducted to investigate the causality, impact, and inherent risks of this growing patient population. PURPOSE: The purpose of this study was to analyze the hypothesis that type II diabetes inhibits the formation of a solid bony union after spinal fusion surgery by altering the local microenvironment at the fusion site through a reduction in growth factors critical for bone formation. STUDY/DESIGN SETTING: In vivo rodent model of type II diabetes. PATIENT SAMPLE: Not applicable. OUTCOME MEASURES: Growth factor analysis, micro CT, manual palpation for fusion evaluation, Faxitron radiographs, and histology. METHODS: 20 control (Sprague Dawley, SD) and 30 diabetic (Zucker Diabetic Sprague Dawley, ZDSD) rats were obtained at 5 weeks of age. Blood glucose (BG) and weight were monitored on ZDSD rats bi-weekly and monthly on controls. Glycated hemoglobin (HbA1c) was measured at surgery and sacrifice on all animals. At 20 weeks of age all animals underwent posterolateral and laminar fusion surgery using a tailbone autograft implanted into the L4-L5 transverse processes. 6 control and 10 ZDSD rats were sacrificed 1 week postsurgery for growth factor analysis. The rest were sacrificed 3 months postsurgery (32 weeks of age) for fusion evaluation via manual palpation, uCT, faxitron X-ray, and histology. RESULTS: There were significantly fewer manual palpation fusions in the ZDSD rats (50%) compared to SD control rats, (86%), Figure 1A. Patterns of weight gain were also significantly different between the two strains with less weight gain over the follow-up period in the ZDSD rats (average beta change in weight, 6.78±3.76) compared to SD control rats (11.86±2.07), p<0.001. Blood glucose was significantly higher at both the surgical and sacrifice time points in the ZDSD rats compared to SD controls, and HbA1c was correspondingly and significantly increased. The ZDSD rat strain did not decisively yield a diabetic condition as only 60% of ZDSD rats actually demonstrated diabetes as defined by a BG>250 mmol/L. Growth factor assay of fusion site explants at early sacrifice demonstrated PDGF was marginally upregulated in the ZDSD rats. TGFB, IGF, and VEGF were not statistically different between groups. Bone mineral density (BMD) as determined by micro CT was significantly lower in ZDSD rats compared to SD controls and was a significant function of HbA1c, p<0.0001 Figure 1B. Micro CT measures of bone volume were not significantly different between groups. CONCLUSIONS: Data generated in this in vivo rat model of T2DM demonstrate that the metabolic dysregulation associated with the diabetic condition negatively impacts both the rate of fusion and density of the formed fusion mass. Increased measures of diabetic status, as determined by BG and HbA1c, were correlated with decreased quality of formed fusion, highlighting the importance of diabetic status monitoring and regulation to bone health, particular during bone healing. FDA Device/Drug Status of all medical devices/medications discussed: Not applicable. https://doi.org/10.1016/j.spinee.2017.07.331
NASS 32nd Annual Meeting Proceedings / The Spine Journal 17 (2017) S89–S110
nificantly more bone through growth by microCT compared to PEEK with average bone coverage scores of 1.62±0.89 and 0.43±0.51 respectively at 4 weeks (p<.01) and 1.79±1.19 and 0.69±0.87 respectively at 8 weeks (p<.05). The radiographic appearance of the bone growing through apertures with titanium was more robust and more mature than PEEK at all time points. Furthermore, bone grew more quickly in the group with a titanium surface as evidenced by higher bone formation at 4 weeks compared to the PEEK group at 8 weeks. Histology corroborated these findings by demonstrating new bone formation in direct apposition to titanium surfaces both inside the apertures and on the implant surface. CONCLUSIONS: A commercially pure titanium surface on PEEK resulted in higher quantity and faster rate of bone growth compared to identical unmodified PEEK implants in this sheep study. FDA DEVICE/DRUG STATUS: N/A, (510k Cleared Devices) (Approved for this indication).
median fusion score for the Vitrium group also increased significantly in Area B. Mean % bone increased significantly for both groups with time as residual implant reduced for the Vitrium group. Mean % bone was significantly higher for Vitrium at 26 weeks. While Vitrium was associated with a macrophage and GC response (significantly higher than PEEK at 8 weeks), scores reduced between 8 and 26 weeks (significantly for macrophages) to levels that were not significantly different to PEEK and therefore is not considered a safety issue. CONCLUSIONS: Vitrium, when filled with autograft, performed significantly better than PEEK filled with autograft at 26 weeks based on a significantly higher mean percent bone and the fact that at 26 weeks the radiographic and microscopic median fusion scores were high in the area initially occupied by Vitrium. FDA DEVICE/DRUG STATUS: Vitrium Cervical IBD (Not approved for this indication).
https://doi.org/10.1016/j.spinee.2017.07.144
https://doi.org/10.1016/j.spinee.2017.07.145
120. Vitrium Bioactive Glass Cervical Interbody Device Ovine Study Janet Krevolin, PhD1, Casey S. Lewis, MEng1, Peggy Lalor, PhD2, Howard B. Seim III, DVM3, Jeremiah T. Easley, DVM4; 1Bio2 Technologies, Woburn, MA, US; 2Histion, Everett, WA, US; 3Colorado State University, Fort Collins, CO, US; 4Preclinical Surgical Research Laboratory, Colorado State University, Fort Collins, CO, US
121. Peptide Amphiphiles Serve as Improved Delivery Vehicles for rhBMP-2 in a Rabbit Spine Fusion Model Gurmit Singh, BS1,2, Mark McClendon, PhD2,3, Sungsoo Seth Lee, PhD2,3,4, Karina Katchko, BS1,2, Andrew Schneider, MD, BA1,2, Joseph A. Weiner, BS1,2, Ralph W. Cook IV, BS1,2, Danielle S. Chun1,2, Michael S. Schallmo, BS1,2, Jonghwa Yun1, Anjan Ghosh1, Chawon Yun, PhD1,2, Soyeon Jeong1,2, Samuel I. Stupp, PhD2,3,4, Erin L. Hsu, PhD1,2, Wellington K. Hsu, MD1,2; 1Northwestern University, Department of Orthopaedic Surgery, Chicago, IL, US; 2Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, US; 3Department of Materials Science and Engineering, Northwestern University, Evanston, IL, US; 4Department of Biomedical Engineering, Northwestern University, Evanston, IL, US
BACKGROUND CONTEXT: Anterior cervical discectomy and fusion (ACDF) is an established treatment option for symptomatic degenerative disc disease. Current interbody materials used for ACDF are not resorbable, bioactive nor osteoconductive which result in clinical compromises. There are clear advantages of an osteoconductive, bioactive and resorbable implant: a) the ability to load shift from the implant to newly formed bone, b) avoidance of long-term stress shielding and c) elimination of imaging interference. PURPOSE: The purpose of this study was to evaluate implant resorption, fusion mass and tissue ingrowth into the resorbable Vitrium® bioactive glass interbody device and compare fusion performance to a PEEK control. STUDY DESIGN/SETTING: N/A. PATIENT SAMPLE: N/A. OUTCOME MEASURES: N/A. METHODS: Vitrium cervical IBDs were manufactured by mixing resorbable glass fibers with a binder, pore former and a liquid into a plastically moldable material and sintered to form a bioactive implant. The IBDs had an interconnected open pore network with a bulk porosity ranging from 35– 45% with both micro and macropores (100 µm-600 µm). Sheep underwent instrumented lumbar interbody fusion with autograft at L2-L3 and L4-L5 with a Vitrium or PEEK IBD. Specimens harvested at 0, 8 and 26 weeks were radiographed and embedded in methyl methacrylate. One ground section was taken from the lateral, central and medial aspects of each implant and stained with Stevenel’s blue/van Gieson stain. Fusion assessments were made semiquantitatively for two different areas: Area A (the areas available inside and outside the implants) and Area B (the area occupied by the resorbable implant) using radiographs and stained slides. Stained sections were evaluated quantitatively (histomorphometrically) for percent bone, percent residual implant material, percent residual graft, percent fibrous tissue, and percent chondral tissue. Necrosis and cellular parameters including lymphocytes, polymorphonuclear leukocytes, macrophages, giant cells (GCs), and plasma cells were also scored. RESULTS: Median radiograph fusion at 8 weeks was similar for both groups indicative of less than 10% connectivity between the vertebral bodies in Area A. The median score for fusion in Area A increased significantly between 8 weeks and 26 weeks for both groups with no significant difference at 26 weeks. For the Vitrium group there was radiographically evident connectivity achieved between vertebral bodies across Area B, with median scores increasing significantly between 8 weeks and 26 weeks to a connectivity level greater than 75%. Histology at 8 weeks showed that chondral tissue largely prevented fusion in both groups. Median fusion scores increased significantly for both groups between 8 and 26 weeks, the
BACKGROUND CONTEXT: Advances in biologics and other bone graft substitutes have decreased the rate of pseudarthrosis; however, there still exists a need for a product that elicits high fusion rates with minimal adverse effects. Recombinant human bone morphogenetic protein-2 (rhBMP-2) applied onto an absorbable collagen sponge (ACS) results in fusion rates of >90% in humans. However, the supraphysiologic dose of rhBMP-2 required with this vehicle can lead to serious complications. In previous work, we developed nanofiber scaffolds composed of peptide amphiphiles (PA) that are capable of delivering exogenous rhBMP-2. Additionally, we have further modified this PA to include an rhBMP-2 binding motif. PURPOSE: The purpose of this study was to evaluate the delivery of rhBMP-2 via non-binding PA or BMP-binding PA with the intent of reducing the amount of exogenous growth factor necessary to achieve bone regeneration and successful spine fusion in a rabbit posterolateral fusion (PLF) model. STUDY DESIGN/SETTING: N/A. PATIENT SAMPLE: N/A. OUTCOME MEASURES: N/A. METHODS: New Zealand white rabbits underwent bilateral PLF at L5L6 with either 30 µg or 60 µg of rhBMP-2 per animal (15 µg or 30 µg of rhBMP-2 per side) loaded onto BMP-binding PA with collagen, nonbinding PA with collagen, or collagen sponge. Spine fusion was assessed using radiographs, fusion scoring and microCT imaging. Fusion scores were determined by blinded manual palpation using an established scoring system: 0=no bridging bone, 1=unilateral bridging, and 2=bilateral bridging. Spines with an average score ≥1 were considered fused. New bone volume was assessed by microCT analysis. One-way ANOVA with Tukey’s post-hoc was used to evaluate for differences between groups with continuous variables. RESULTS: Rabbits treated with BMP-binding PA or non-binding PA loaded with 30 µg or 60 µg of rhBMP-2 (per animal) demonstrated significantly higher fusion scores by manual palpation than those treated with equivalently pre-loaded collagen sponge (2.0, 1.61 and 0.0, respectively, for 30 µg of rhBMP-2; 2.0, 2.0 and 1.04, respectively, for 60 µg of rhBMP-2; p<.05). Fusion scores between BMP-binding PA and non-binding PA preloaded with
NASS 32nd Annual Meeting Proceedings / The Spine Journal 17 (2017) S89–S110 equivalent doses of rhBMP-2 showed no significant difference. Furthermore, there was no significant difference between both doses of rhBMP-2 for binding PA or non-binding PA. BMP-binding PA loaded with 30 µg rhBMP-2 demonstrated significantly higher new bone volume than equally loaded collagen sponge as assessed by microCT (p<.05). There were no other significant differences in new bone volume as per microCT between the nonbinding PA group vs. collagen sponge group and the non-binding PA group vs. BMP-binding PA group all preloaded with 30 µg of rhBMP-2. CONCLUSIONS: Currently, ACS is the only approved carrier for rhBMP2. Our data suggests that both BMP-binding and non-binding PA are better carriers for rhBMP-2 compared to an equivalently loaded collagen sponge. Furthermore, these scaffolds can effectively reduce the dose requirement necessary for spinal fusion relative to collagen sponge alone. Although future studies will identify the lowest rhBMP-2 loading dose at which the BMPbinding or non-binding PA can promote fusion rates approaching 100%, our results indicate the BMP-binding PA is more promising. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs. https://doi.org/10.1016/j.spinee.2017.07.146
122. Radiographic and CT Evaluation of Recombinant Human Bone Morphogenetic Protein-2-Assisted Cervical Spinal Interbody Fusion Luke J. Weisbrod1, John D. Leever, MD2, J. Kenneth Burkus, MD3, Kevin T. Foley, MD, FACS4, Randall F. Dryer, MD5, Paul M. Arnold, MD6; 1US; 2The University of Kansas Hospital, Kansas City, KS, US; 3The Hughston Clinic, PC, Columbus, GA, US; 4SemmesMurphey Clinic, Memphis, TN, US; 5Central Texas Spine Institute, L.L.P., Austin, TX, US; 6University of Kansas Medical Center/Department of Neurosurgery, Kansas City, KS, US BACKGROUND CONTEXT: N/A. PURPOSE: Studies investigating rhBMP-2 assisted spinal fusion have yielded promising results, suggesting rhBMP-2 as an efficacious alternative to iliac crest autografts. Spinal fusion assisted by rhBMP-2 both hastens healing and eliminates patient morbidity from iliac crest autograft. Unique to BMPassisted spinal fusion is its distinct radiographic fusion pattern as fusion is achieved. Despite promising results and increased clinical use of rhBMP2, there remains a paucity of literature documenting this radiographic process. The objective of this study is to radiographically demonstrate the distinct fusion pattern of rhBMP-2 in the setting of ACDF. STUDY DESIGN/SETTING: N/A. PATIENT SAMPLE: N/A. OUTCOME MEASURES: N/A. METHODS: This study included 26 patients who underwent single-level anterior cervical discectomy and fusion using rhBMP-2. RESULTS: A polyetheretherketone cage was used as an interbody disc spacer in all 26 patients. Patients were evaluated between 2 and 6 weeks after surgery and subsequently at 3,6,12 and 24 months post-op. All patients underwent plain radiography at every follow-up visit, and CT evaluation was performed at 3,6,12 and 24 months as part of the study protocol. CONCLUSIONS: rhBMP-2 leads to both successful interbody fusion and an enhanced fusion rate with unique imaging characteristics. Additional characteristics of BMP observed in 100% of patients included prevertebral soft-tissue swelling and early endplate resorption. Other common features included PEEK cage migration, heterotopic bone formation and subsidence of the cage. FDA DEVICE/DRUG STATUS: rhBMP-2 (Not approved for this indication). https://doi.org/10.1016/j.spinee.2017.07.147
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Research Grant Award Winner The Impact of Type 2 Diabetes on Bone Metabolism and Growth after Spinal Fusion Neil Bhamb, MD, Linda E.A. Kanim, MA, Ruben Maldonado, BS, Trevor Nelson, BS, Juliane Glaeser, PhD, Melodie F. Metzger, PhD BACKGROUND CONTEXT: Diabetes mellitus is a chronic metabolic disease with an enormous impact on public health. The incidence of type II diabetes (T2DM) has skyrocketed to epidemic proportions and is expected to rise. As the prevalence of diabetes continues to increase, so does the percentage of diabetics among patients undergoing spinal fusion surgery. Some clinical reports suggest diabetes may have a negative effect on spinal fusion outcomes, although no conclusive experimental research has been conducted to investigate the causality, impact, and inherent risks of this growing patient population. PURPOSE: The purpose of this study was to analyze the hypothesis that type II diabetes inhibits the formation of a solid bony union after spinal fusion surgery by altering the local microenvironment at the fusion site through a reduction in growth factors critical for bone formation. STUDY/DESIGN SETTING: In vivo rodent model of type II diabetes. PATIENT SAMPLE: Not applicable. OUTCOME MEASURES: Growth factor analysis, micro CT, manual palpation for fusion evaluation, Faxitron radiographs, and histology. METHODS: 20 control (Sprague Dawley, SD) and 30 diabetic (Zucker Diabetic Sprague Dawley, ZDSD) rats were obtained at 5 weeks of age. Blood glucose (BG) and weight were monitored on ZDSD rats bi-weekly and monthly on controls. Glycated hemoglobin (HbA1c) was measured at surgery and sacrifice on all animals. At 20 weeks of age all animals underwent posterolateral and laminar fusion surgery using a tailbone autograft implanted into the L4-L5 transverse processes. 6 control and 10 ZDSD rats were sacrificed 1 week postsurgery for growth factor analysis. The rest were sacrificed 3 months postsurgery (32 weeks of age) for fusion evaluation via manual palpation, uCT, faxitron X-ray, and histology. RESULTS: There were significantly fewer manual palpation fusions in the ZDSD rats (50%) compared to SD control rats, (86%), Figure 1A. Patterns of weight gain were also significantly different between the two strains with less weight gain over the follow-up period in the ZDSD rats (average beta change in weight, 6.78±3.76) compared to SD control rats (11.86±2.07), p<0.001. Blood glucose was significantly higher at both the surgical and sacrifice time points in the ZDSD rats compared to SD controls, and HbA1c was correspondingly and significantly increased. The ZDSD rat strain did not decisively yield a diabetic condition as only 60% of ZDSD rats actually demonstrated diabetes as defined by a BG>250 mmol/L. Growth factor assay of fusion site explants at early sacrifice demonstrated PDGF was marginally upregulated in the ZDSD rats. TGFB, IGF, and VEGF were not statistically different between groups. Bone mineral density (BMD) as determined by micro CT was significantly lower in ZDSD rats compared to SD controls and was a significant function of HbA1c, p<0.0001 Figure 1B. Micro CT measures of bone volume were not significantly different between groups. CONCLUSIONS: Data generated in this in vivo rat model of T2DM demonstrate that the metabolic dysregulation associated with the diabetic condition negatively impacts both the rate of fusion and density of the formed fusion mass. Increased measures of diabetic status, as determined by BG and HbA1c, were correlated with decreased quality of formed fusion, highlighting the importance of diabetic status monitoring and regulation to bone health, particular during bone healing. FDA Device/Drug Status of all medical devices/medications discussed: Not applicable. https://doi.org/10.1016/j.spinee.2017.07.331