Osteogenic factors are often used in orthopedics to promote bone growth, improve fracture healing, and induce spine fusion. Osteogenic oxysterols are naturally occurring molecules that were shown to induce osteogenic differentiation in vitro and promote spine fusion in vivo. The purpose of this study was to identify an osteogenic oxysterol more suitable for clinical development than those previously reported, and evaluate its ability to promote osteogenesis in vitro and spine fusion in rats in vivo. Among more than 100 oxysterol analogues synthesized, Oxy133 induced significant expression of osteogenic markers Runx2, osterix (OSX), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN) in C3H10T1/2 mouse embryonic fibroblasts and in M2-10B4 mouse marrow stromal cells. Oxy133-induced activation of an 8×-Gli luciferase reporter, its direct binding to Smoothened, and the inhibition of Oxy133-induced osteogenic effects by the Hedgehog (Hh) pathway inhibitor, cyclopamine, demonstrated the role of Hh pathway in mediating osteogenic responses to Oxy133. Oxy133 did not stimulate osteogenesis via BMP or Wnt signaling. Oxy133 induced the expression of OSX, BSP, and OCN and stimulated robust mineralization in primary human mesenchymal stem cells. In vivo, bilateral spine fusion occurred through endochondral ossification and was observed in animals treated with Oxy133 at the fusion site on xray after 4 weeks and confirmed with manual assessment, micro CT (μCT), and histology after 8 weeks, with equal efficiency to recombinant human bone morphogenetic protein-2 (rhBMP-2). Unlike rhBMP-2, Oxy133 did not induce adipogenesis in the fusion mass and resulted in denser bone evidenced by greater BV/TV ratio and smaller trabecular separation. Findings here suggest that Oxy133 has significant potential as an osteogenic molecule with greater ease of synthesis and improved time to fusion compared to previously studied oxysterols. Small molecule osteogenic oxysterols may serve as the next generation of bone anabolic agents for therapeutic development.

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Cervical spine studies that aim to investigate kyphotic deformities should make efforts to discern the different subtypes of kyphotic deformities to more accurately characterize and study the effects that the sagittal alignment has on the kinematics of the spine and the degree of spinal cord compression.

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The present study aimed to evaluate the analgesic effect of the antioxidant nanoparticle fullerol in a mouse radiculopathy and a dorsal root ganglion (DRG) culture models. Intervertebral disc degeneration causes significant hyperalgesia and nerve inflammation. Pain sensitization and inflammatory reaction were counteracted by fullerol when disc material was bathed in 10 or 100µM of fullerol prior to implantation. Immunohistochemistry showed similar massive IBA1 positive macrophage infiltration surrounding implanted disc material among groups, but IL-1β and IL-6 expression was decreased in fullerol treated group. In the DRG explant culture, after treatment with TNF-α, the expression of IL-1β, NLRP3, and caspase 1 was significantly increased but this was reversed by the addition of fullerol. In addition, fullerol also decreased the expression of substance P and CGRP in the cultured DRGs. Nanoparticle fullerol effectively counteracts pain sensitization and the inflammatory cascade caused by disc degeneration.

Growth factors are of great potential in regenerative medicine. However, their clinical applications are largely limited by the short in vivo half-lives and the narrow therapeutic window. Thus, a robust controlled release system remains an unmet medical need for growth-factor-based therapies. In this research, a nanoscale controlled release system (degradable protein nanocapsule) is established via in situ polymerization on growth factor. The release rate can be finely tuned by engineering the surface polymer composition. Improved therapeutic outcomes can be achieved with growth factor nanocapsules, as illustrated in spinal cord fusion mediated by bone morphogenetic protein-2 nanocapsules.

Study Design: This was a systematic review and meta-analysis. Objective: This study aims to perform a systematic review and quantitative meta-analysis of patient-reported outcome measures after spinal fusion for adolescent idiopathic scoliosis (AIS). Summary of Background Data: Radiographic correction of scoliosis is extensively reported in the literature but there is a need to study the impact of spinal fusion on patient-reported outcome measures. Prior reviews lacked homogeneity in outcome measures, did not perform quantitative meta-analysis of pooled effect size, or interpret the results in light of minimally clinically important difference thresholds. Materials and Methods: A systematic review of medical databases identified all studies that prospectively reported Scoliosis Research Society (SRS)-22 questionnaire data after spinal fusion for AIS. We screened 2314 studies for eligibility. Studies were included that reported preoperative and postoperative data at 24- or >60-month follow-up. Studies were excluded that failed to report means and SDs which were needed to calculate Cohen d effect sizes and 95% confidence intervals in estimating the magnitude and precision of the effect. Results: A total of 7 studies met eligibility criteria for inclusion in quantitative meta-analysis of effect sizes and 95% confidence intervals. Patients report large improvements in total score, self-image, and satisfaction; and moderate improvements in pain, function and mental health at 2 and 5 years after spinal fusion for AIS. All domains showed statistically significant improvement at all times except function at >60 months. All domains surpassed the minimally clinically important difference at all times except mental health. Conclusions: Moderate evidence suggests that spinal fusion improves quality of life for adolescents with idiopathic scoliosis in medium and long-term follow-up. Our results may help inform patient expectations regarding surgery. OCEMB Level of Evidence: Level I—systematic review and meta-analysis of prospective studies.