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

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

In vivo evaluation of bioresorbable polylactide implants for cervical graft containment in an ovine spinal fusion model.

OBJECT: An in vivo study was conducted in an ovine model to investigate the biomechanical changes after the animals underwent single-level anterior cervical discectomy followed by fusion in which autologous tricortical graft was used and implantation of cervical plates for which bioresorbable polymer screws and plates were used. The specific aims of the study were to evaluate whether implant failure or screw backout would occur over time and to measure the change in stiffness at the treated level at various postoperative time periods (3, 6, and 12 months). METHODS: A total of 58 x-ray films were evaluated over the 12-month survival period. No screw breakage or displacement was observed in any animal during the temporal radiographic analysis. Radiographically confirmed fusion appeared to be complete at all time periods longer than 6 months. The biomechanical testing demonstrated dramatic reductions in range of motion at the fusion level in the animals allowed to survive for 6 and 12 months, indicating complete fusion after 6 months. CONCLUSIONS: The bioresorbable polymer cervical graft containment system appears to provide a safe and effective alternative for cervical fusion, and warrants further clinical evaluation for its use in single-level anterior cervical discectomy and fusion without postoperative orthosis

In vivo evaluation of bioresorbable polylactide implants for cervical graft containment in an ovine spinal fusion model

OBJECT: An in vivo study was conducted in an ovine model to investigate the biomechanical changes after the animals underwent single-level anterior cervical discectomy followed by fusion in which autologous tricortical graft was used and implantation of cervical plates for which bioresorbable polymer screws and plates were used. The specific aims of the study were to evaluate whether implant failure or screw backout would occur over time and to measure the change in stiffness at the treated level at various postoperative time periods (3, 6, and 12 months). METHODS: A total of 58 x-ray films were evaluated over the 12-month survival period. No screw breakage or displacement was observed in any animal during the temporal radiographic analysis. Radiographically confirmed fusion appeared to be complete at all time periods longer than 6 months. The biomechanical testing demonstrated dramatic reductions in range of motion at the fusion level in the animals allowed to survive for 6 and 12 months, indicating complete fusion after 6 months. CONCLUSIONS: The bioresorbable polymer cervical graft containment system appears to provide a safe and effective alternative for cervical fusion, and warrants further clinical evaluation for its use in single-level anterior cervical discectomy and fusion without postoperative orthosis

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

NELL-1 in the treatment of osteoporotic bone loss.

NELL-1 is a secreted, osteoinductive protein whose expression rheostatically controls skeletal ossification. Overexpression of NELL-1 results in craniosynostosis in humans and mice, whereas lack of Nell-1 expression is associated with skeletal undermineralization. Here we show that Nell-1-haploinsufficient mice have normal skeletal development but undergo age-related osteoporosis, characterized by a reduction in osteoblast:osteoclast (OB:OC) ratio and increased bone fragility. Recombinant NELL-1 binds to integrin β1 and consequently induces Wnt/β-catenin signalling, associated with increased OB differentiation and inhibition of OC-directed bone resorption. Systemic delivery of NELL-1 to mice with gonadectomy-induced osteoporosis results in improved bone mineral density. When extended to a large animal model, local delivery of NELL-1 to osteoporotic sheep spine leads to significant increase in bone formation. Altogether, these findings suggest that NELL-1 deficiency plays a role in osteoporosis and demonstrate the potential utility of NELL-1 as a combination anabolic/antiosteoclastic therapeutic for bone loss