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Fluorinated diamond-like carbon (F-DLC) coating is biologically safe, provides superior antibacterial properties, and shows promise in preventing postoperative peri-implant infections. However, potential negative effects of this coating on in vivo bone formation and resorption have not been studied. The authors investigated the effects of F-DLC coatings on bone union in beagle dogs. Seventy-two solid columns of titanium alloy were prepared with equally spaced slits. Half of these columns were coated with F-DLC (Group F), and the others were left uncoated as controls (Group C). Columns were implanted in the femurs of beagle dogs, and in vivo bone formation and resorption were assessed 4, 8, and 12 weeks after implantation. In comparison to Group C, Group F showed significantly greater bone volume and trabecular thickness at Week 8 (p &lt, 0.05) and Week 12 (p &lt, 0.005) and significantly lower bone resorption activity, measured by the ratio of osteoclasts to bone surface and of eroded surface to bone surface, at Week 12 (p &lt, 0.05). The F-DLC coating encouraged bone formation in vivo more effectively than uncoated titanium alloy, suggesting that F-DLC will prove to be a useful coating material for antibacterial intraosseous implants.

We fabricated Ti-6Al-7Nb bone scaffolds with 5 mm diameter and 20 mm length comprise of a three-dimensional (3D) honeycomb frame structure of truncated octahedra created by selective laser sintering 3D printing. The honeycomb frame was then coated with 0.1 μm thick diamond-like carbon (DLC) to increase biocompatibility. A round rod of Ti-6Al-7Nb alloy (ASTM F1295) was as a control material. They were implanted into the femur bones of beagles to evaluate bone morphometrics and to investigate changes in the transcriptome of the new bone tissue using DNA microarray analysis and real-time polymerase chain reaction (PCR). In the present report, the 3D honeycomb material with and without DLC film consisting of a-C:H is referred to as 3D_a-C:H and 3D_non, respectively. At 3 weeks after implantation, the 3D_non had more contact between the new and artificial bones compared with the control, and the 3D_a-C:H had more contact between the new and artificial bones compared with the control and 3D_non. Furthermore, 3D_a-C:H showed even more new bone compared with the control and 3D_non. At 8 weeks after implantation, more appeared lamellar bone with the 3D_a-C:H implant than those with the control and 3D_non. The real-time PCR results at 1 week of implantation revealed higher expression levels of VEGF, RANKL, and NOTCH2 expression with 3D_a-C:H than with 3D_non and control. As a result of real-time PCR at 2 weeks of implantation, OPN and CTSK expressions were found to be higher with 3D_a-C:H and 3D_non than that with the control.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population., Koda et al. present the results of a randomized phase 3 trial comparing granulocyte colony-stimulating factor versus placebo in patients with acute spinal cord injury. While the primary endpoint was not met, a sub-analysis revealed a trend towards superior efficacy of G-CSF versus placebo in an elderly population.

Introduction Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. Methods and analysis The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m 2 /day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). Ethics and dissemination The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. Trial registration number UMIN000018752.