Direct Current Electrical Stimulation Increases the Fusion Rate of Spinal Fusion Cages

Study Design. A randomized experimental evaluation of direct current stimulation in a validated animal model with an experimental control group, using blinded radiographic, biomechanical, histologic, and statistical measures. Objectives. To evaluate the efficacy of the adjunctive use of direct current stimulation on the fusion rate and speed of healing of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. Summary of Background Data. Titanium lumbar interbody spinal fusion cages have been reported to be 90% effective for single-level lumbar interbody fusion. However, fusion rates are reported to be between 70% and 80% in patients with multilevel fusions or with risk factors such as obesity, tobacco use, or metabolic disorders. The authors hypothesized that direct current stimulation would increase the fusion rate of titanium interbody fusion cages packed with autograft in a sheep lumbar interbody fusion model. Methods. Twenty-two sheep underwent lumbar discectomy and fusion at L4–L5 with an 11- × 20-mm Bagby and Kuslich (BAK) cage packed with autograft. Seven sheep received a BAK cage and no current. Seven sheep had a cage and a 40-μA current applied with a direct current stimulator. Eight sheep had a BAK cage and a 100-μA current applied. All sheep were killed 4 months after surgery. The efficacy of electrical stimulation in promoting interbody fusion was assessed by performing radiographic, biomechanical, and histologic analyses in a blinded fashion. Results. The histologic fusion rate increased as the direct current dose increased from 0 μA to 40 μA to 100 μA (P \u3c 0.009). Histologically, all animals in the 100-μA group had fusions in both the right and left sides of the cage. Direct current stimulation had a significant effect on increasing the stiffness of the treated motion segment in right lateral bending (P \u3c 0.120), left lateral bending (P \u3c 0.017), right axial rotation (P \u3c 0.004), left axial rotation (P \u3c 0.073), extension (P \u3c 0.078), and flexion (P \u3c 0.029) over nonstimulated levels. Conclusion. Direct current stimulation increased the histologic and biomechanical fusion rate and the speed of healing of lumbar interbody spinal fusion cages in an ovine model at 4 months

Polyetheretherketone as a Biomaterial for Spinal Applications

Threaded lumbar interbody spinal fusion devices (TIBFD) made from titanium have been reported to be 90% effective for single-level lumbar interbody fusion, although radiographic determination of fusion has been intensely debated in the literature. Using blinded radiographic, biomechanic, histologic, and statistical measures, we evaluated a radiolucent polyetheretherketone (PEEK)-threaded interbody fusion device packed with autograft or rhBMP-2 on an absorbable collagen sponge in 13 sheep at 6 months. Radiographic fusion, increased spinal level biomechanical stiffness, and histologic fusion were demonstrated for the PEEK cages filled with autograft or rhBMP-2 on a collagen sponge. No device degradation or wear debris was observed. Only mild chronic inflammation consisting of a few macrophages was observed in peri-implant tissues. Based on these results, the polymeric biomaterial PEEK may be a useful biomaterial for interbody fusion cages due to the polymer\u27s increased radiolucency and decreased stiffness

Bioresorbable Polylactide Interbody Implants in an Ovine Anterior Cervical Discectomy and Fusion Model: Three-Year Results

Study Design. In vivo study of anterior discectomy and fusion using a bioresorbable 70:30 poly(l-lactide-co-d,l-lactide) interbody implant in an ovine model. Objective. To evaluate the efficacy of the polylactide implant to function as an interbody fusion device, and to assess the tissue reaction to the material during the resorption process. Summary of Background Data. The use of polylactide as a cervical interbody implant has several potential advantages when compared with traditional materials. Having an elastic modulus very similar to bone minimizes the potential for stress shielding, and as the material resorbs additional loading is transferred to the developing fusion mass. Although preclinical and clinical studies have demonstrated the suitability of polylactide implants for lumbar interbody fusion, detailed information on cervical anterior cervical discectomy and fusion (ACDF) with polylactide devices is desirable. Methods. Single level ACDF was performed in 8 skeletally mature ewes. Bioresorbable 70:30 poly (l-lactide-co-d,l-lactide) interbody implants packed with autograft were used with single-level metallic plates. Radiographs were made every 3 months up to 1 year, and yearly thereafter. The animals were killed at 6 months (3 animals), 12 months (3 animals), and 36 months (2 animals). In addition to the serial plain radiographs, the specimens were evaluated by nondestructive biomechanical testing and undecalcified histologic analysis. Results. The bioresorbable polylactide implants were effective in achieving interbody fusion. The 6-month animals appeared fused radiographically and biomechanically, whereas histologic sections demonstrated partial fusion (in 3 of 3 animals). Radiographic fusion was confirmed histologically and biomechanically at 12 months (3 of 3 animals) and 36 months (2 of 2 animals). A mild chronic inflammatory response to the resorbing polylactide implant was observed at both 6 months and 12 months. At 36 months, the operative levels were solidly fused and the implants were completely resorbed. No adverse tissue response was observed in any animal at any time period. Conclusion. Interbody fusion was achieved using bioresorbable polylactide implants, with no evidence of implant collapse, extrusion, or adverse tissue response to the material. The use of polylactide as a cervical interbody device appears both safe and effective based on these ACDF animal model results

Histologic Evaluation of the Efficacy of rhBMP-2 Compared With Autograft Bone in Sheep Spinal Anterior Interbody Fusion

Study Design. The sheep anterior lumbar spinal fusion model was used to study the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)–collagen composite in comparison with autograft to enhance spinal interbody fusion. Comparisons were drawn from temporal radiographic and end-point biomechanical and histologic data. Objective. To analyze histologically the ability of rhBMP-2 to achieve complete arthrodesis between vertebral bodies. Summary of Background Data. Studies using rhBMP for enhancement of anterior interbody fusion have used numerous endpoints. However, systematic histologic evaluation of the fusion has not been conducted. Methods. Twelve sheep underwent single-level anterior lumbar interbody fusion performed with a cylindrical fenestrated titanium interbody fusion device (INTER FIX, Medtronic Sofamor Danek, Inc., Memphis, TN). The device was filled either with rhBMP-2–collagen (n = 6) or autogenous iliac crest bone graft (n = 6). Radiologic evaluation was carried out at 2-month intervals, and all sheep were killed 6 months after surgery. Nondestructive biomechanical testing for stiffness to flexion, extension, and lateral bending moments, un-decalcified histology, and qualitative and quantitative histologic evaluation were performed. Results. Radiographs revealed a bony bridge anterior to the cage in five of six rhBMP-2-treated animals, whereas it was present only in one of five in the autogenous bone graft group. Segments treated with rhBMP-2 were 20% stiffer in flexion than autograft-treated segments at 6 months. Six of six in the rhBMP-2 group and two of six in the autograft group showed complete fusion. There was a significantly higher rate of bony continuity observed at the fenestrations of the rhBMP-2 group. Three times more number of cage fenestrations in the rhBMP-2 group demonstrated “all-bone” when compared with the autograft group (P \u3c 0.001). Further, the scar tissue in and around the autograft-treated cages was 16-fold more (P \u3c 0.01) than that seen for rhBMP-2-treated cages. Conclusions. The study demonstrates that rhBMP-2 can lead to earlier radiologic fusion and a more consistent increased stiffness of the segments when compared with autograft in sheep anterior lumbar interbody fusion. Furthermore, a three times higher histologic fusion rate is attainable with significantly reduced fibrous tissue around the implant when rhBMP-2 is used

Bony ingrowth potential of 3D-printed porous titanium alloy: a direct comparison of interbody cage materials in an in vivo ovine lumbar fusion model.

Background contextThere is significant variability in the materials commonly used for interbody cages in spine surgery. It is theorized that three-dimensional (3D)-printed interbody cages using porous titanium material can provide more consistent bone ingrowth and biological fixation.PurposeThe purpose of this study was to provide an evidence-based approach to decision-making regarding interbody materials for spinal fusion.Study designA comparative animal study was performed.MethodsA skeletally mature ovine lumbar fusion model was used for this study. Interbody fusions were performed at L2-L3 and L4-L5 in 27 mature sheep using three different interbody cages (ie, polyetheretherketone [PEEK], plasma sprayed porous titanium-coated PEEK [PSP], and 3D-printed porous titanium alloy cage [PTA]). Non-destructive kinematic testing was performed in the three primary directions of motion. The specimens were then analyzed using micro-computed tomography (µ-CT); quantitative measures of the bony fusion were performed. Histomorphometric analyses were also performed in the sagittal plane through the interbody device. Outcome parameters were compared between cage designs and time points.ResultsFlexion-extension range of motion (ROM) was statistically reduced for the PTA group compared with the PEEK cages at 16 weeks (p-value=.02). Only the PTA cages demonstrated a statistically significant decrease in ROM and increase in stiffness across all three loading directions between the 8-week and 16-week sacrifice time points (p-value≤.01). Micro-CT data demonstrated significantly greater total bone volume within the graft window for the PTA cages at both 8 weeks and 16 weeks compared with the PEEK cages (p-value<.01).ConclusionsA direct comparison of interbody implants demonstrates significant and measurable differences in biomechanical, µ-CT, and histologic performance in an ovine model. The 3D-printed porous titanium interbody cage resulted in statistically significant reductions in ROM, increases in the bone ingrowth profile, as well as average construct stiffness compared with PEEK and PSP

Transient Local Bone Remodeling Effects of rhBMP-2 in an Ovine Interbody Spine Fusion Model

Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a powerful osteoinductive morphogen capable of stimulating the migration of mesenchymal stem cells (MSCs) to the site of implantation and inducing the proliferation and differentiation of these MSCs into osteoblasts. Vertebral end-plate and vertebral body resorption has been reported after interbody fusion with high doses of rhBMP-2. In this study, we investigated the effects of 2 rhBMP-2 doses on peri-implant bone resorption and bone remodeling at 7 time points in an end-plate-sparing ovine interbody fusion model. Methods: Twenty-one female sheep underwent an end-plate-sparing discectomy followed by interbody fusion at L2-L3 and L4-L5 using a custom polyetheretherketone (PEEK) interbody fusion device. The PEEK interbody device was filled with 1 of 2 different doses of rhBMP-2 on an absorbable collagen sponge (ACS): 0.13 mg (1·) or 0.90 mg (7·). Bone remodeling and interbody fusion were assessed via high-resolution radiography and histological analyses at 1, 2, 3, 4, 8, 12, and 20 weeks postoperatively. Results: Peri-implant bone resorption peaked between 3 and 8 weeks in both the 1· and the 7· rhBMP-2/ACS-dose group. Osteoclastic activity and corresponding peri-implant bone resorption was dose-dependent, with moderate-tomarked resorption at the 7·-dose level and less resorption at the 1·-dose level. Both dose (p \u3c 0.0007) and time (p \u3c 0.0025) affected bone resorption significantly. Transient bone-resorption areas were fully healed by 12 weeks. Osseous bridging was seen at all but 1 spinal level at 12 and at 20 weeks. Conclusions: In the ovine end-plate-sparing interbody fusion model, rhBMP-2 dose-dependent osteoclastic resorption is a transient phenomenon that peaks at 4 weeks postoperatively. Clinical Relevance: Using the U.S. Food and Drug Administration (FDA)-approved rhBMP-2 concentration and matching the volume of rhBMP-2/ACS with the volume of desired bone formation within the interbody construct may limit the occurrence of transient bone resorption

Old traces, read anew - 'The Reading Hermit' painting in the light of X-ray fluorescence

There exist several very similar looking versions of the painting ‘The Reading Hermit’, all allegedly painted by Rembrandt Harmenszoon van Rijn (approx. in ∼1630 A.D., Leiden). The classification of Rembrandt's paintings, which were produced by Rembrandt himself, in his academy by his students and the ones being mere copies is a crucial and difficult task. We gathered background evidence and performed elemental analyses by non-destructive micro-X-ray fluorescence (micro-XRF) in order to elucidate the painting's provenance. Elemental distributions of Ca, Mn, Fe and Cu show that the painting was presumably changed during the painting process, which indicates, together with neutron autoradiography (NAR) investigations, that this version of ‘The Reading Hermit’ is not a copy

Conceptual and Measurement Issues in Assessing Democratic Backsliding

During the past decade, analyses drawing on several democracy measures have shown a global trend of democratic retrenchment. While these democracy measures use radically different methodologies, most partially or fully rely on subjective judgments to produce estimates of the level of democracy within states. Such projects continuously grapple with balancing conceptual coverage with the potential for bias (Munck and Verkuilen 2002; Przeworski et al. 2000). Little and Meng (L&M) (2023) reintroduce this debate, arguing that “objective” measures of democracy show little evidence of recent global democratic backsliding.1 By extension, they posit that time-varying expert bias drives the appearance of democratic retrenchment in measures that incorporate expert judgments. In this article, we engage with (1) broader debates on democracy measurement and democratic backsliding, and (2) L&M’s specific data and conclusions

Overview of the Processes driving Exchange At Cape Hatteras Program

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Seim, H., Savidge, D., Andres, M., Bane, J., Edwards, C., Gawarkiewicz, G., He, R., Todd, R., Muglia, M., Zambon, J., Han, L., & Mao, S. Overview of the Processes driving Exchange at Cape Hatteras Program. Oceanography, (2022), https://doi.org/10.5670/oceanog.2022.205.The Processes driving Exchange At Cape Hatteras (PEACH) program seeks to better understand seawater exchanges between the continental shelf and the open ocean near Cape Hatteras, North Carolina. This location is where the Gulf Stream transitions from a boundary-trapped current to a free jet, and where robust along-shelf convergence brings cool, relatively fresh Middle Atlantic Bight and warm, salty South Atlantic Bight shelf waters together, forming an important and dynamic biogeographic boundary. The magnitude of this convergence implies large export of shelf water to the open ocean here. Background on the oceanography of the region provides motivation for the study and gives context for the measurements that were made. Science questions focus on the roles that wind forcing, Gulf Stream forcing, and lateral density gradients play in driving exchange. PEACH observational efforts include a variety of fixed and mobile observing platforms, and PEACH modeling included two different resolutions and data assimilation schemes. Findings to date on mean circulation, the nature of export from the southern Middle Atlantic Bight shelf, Gulf Stream variability, and position variability of the Hatteras Front are summarized, together with a look ahead to forthcoming analyses.We gratefully acknowledge NSF funding (OCE-1558920 to UNC-CH, OCE-1559476 to SkIO, OCE-1558521 to WHOI, OCE-1559178 to NCSU); technical support from Sara Haines, Craig Marquette, Trip Patterson, Nick DeSimone, Erran Sousa, Gabe Matthias, Patrick Deane, Brian Hogue, Frank Bahr, and Ben Hefner; cruise participants Jacob Forsyth, Joleen Heiderich, Chuxuan Li, Marco Valero, Lauren Ball, John McCord, and Kyle Maddux-Lawrence; and the crew of R/V Armstrong for their able support during three PEACH cruises