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Thrombosis and infections are two grave, interrelated problems associated with the use of central venous catheters (CVL). Currently used antibiotic coated CVL has limited clinical success in resisting blood stream infection and may increase the risk of emerging antibiotic resistant strains. We report an antibiotic-free, fluoropolymer-immobilized, liquid perfluorocarbon-coated peripherally inserted central catheter (PICC) line and its effectiveness in reducing catheter associated thrombosis and pathogen colonization, as an alternative to antibiotic coated CVL. Commercially available polyurethane PICC catheter was modified by a three-step lamination process, with thin fluoropolymer layers to yield fluoropolymer–polyurethane–fluoropolymer composite structure before applying the liquid perfluorocarbon (LP). This high throughput process of modifying commercial PICC catheters with fluoropolymer is quicker, safer and shows higher thromboresistance than fluorinated, omniphobic catheter surfaces, produced by previously reported self-assembled monolayer deposition techniques. The LP immobilized on the fluoropolymer is highly durable in physiological flow conditions for over 60 days and continue to resist Staphylococcus colonization.

Spontaneous mineralization of the nucleus pulposus (NP) has been observed in cases of intervertebral disc degeneration (IDD). Inflammatory cytokines have been implicated in mineralization of multiple tissues through their modulation of expression of factors that enable or inhibit mineralization, including TNAP, ANKH or ENPP1. This study examines the underlying factors leading to NP mineralization, focusing on the contribution of the inflammatory cytokine, TNF, to this pathologic event. We show that human and bovine primary NP cells express high levels of ANKH and ENPP1, and low or undetectable levels of TNAP. Bovine NPs transduced to express TNAP were capable of matrix mineralization, which was further enhanced by ANKH knockdown. TNF treatment or overexpression promoted a greater increase in mineralization of TNAP-expressing cells by downregulating the expression of ANKH and ENPP1 via NF-κB activation. The increased mineralization was accompanied by phenotypic changes that resemble chondrocyte hypertrophy, including increased RUNX2 and COL10A1 mRNA; mirroring the cellular alterations typical of samples from IDD patients. Disc organ explants injected with TNAP/TNF- or TNAP/shANKH-overexpressing cells showed increased mineral content inside the NP. Together, our results confirm interactions between TNF and downstream regulators of matrix mineralization in NP cells, providing evidence to suggest their participation in NP calcification during IDD.

STUDY DESIGN Basic Science. OBJECTIVE To determine if locally delivered simvastatin can enhance bone formation in a rat spinal fusion model. SUMMARY OF BACKGROUND DATA The bone-anabolic properties of statins in fracture healing are well established, however, few studies have evaluated the impact of locally delivered statins in spinal fusion. METHODS We formulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles by adapting previously published techniques. Two types of nanoparticles were created: simvastatin nanoparticles (SimNP) and nanoparticles without simvastatin (BlankNP). Drug elution from SimNP was characterized. Osteoblastic differentiation was analyzed using MC3T3-E1 cells cultured in differentiation medium containing SimNP or BlankNP. Forty male 12 week old outbred Wistar rats underwent uninstrumented posterolateral fusion using iliac crest bone graft and BlankNP, SimNP or simvastatin drug. X-rays to assess bone formation were obtained at 4 weeks and 9 weeks post-operatively. Spines were explanted at 9 weeks for micro-CT analysis, and a blinded manual assessment of fusion (MAF). RESULTS SimNP achieved a release efficiency of 74.1% with ∼50% release occurring in the first day. Simvastatin and SimNP treated cells showed significantly greater expression of osteopontin (OPN) and osteocalcin (OCN). On micro-CT analysis, SimNP animals had higher bone volume and percent bone volume (bone volume/total volume) than control animals. SimNP rats had higher X-ray scores at 4 weeks (p=0.010) and 9 weeks (p

Current guidelines for the optimal treatment degenerative spondylolisthesis are weak and based on limited high-quality evidence. There is some moderate evidence that decompression alone may be a feasible treatment with lower surgical morbidity and similar outcomes to fusion when performed in a select population with a low-grade slip. Similarly, addition of interbody fusion may be best suited to a subset of patients with high-grade degenerative spondylolisthesis, although this remains controversial. Minimally invasive techniques are increasingly being utilized for both decompression and fusion surgeries with more and more studies showing similar outcomes and lower postoperative morbidity for patients. This will likely be an area of continued intense research. Finally, the role of spondylolisthesis reduction will likely be determined as further investigation into optimal sagittal balance and spinopelvic parameters is conducted. Future identification of ideal thresholds for sagittal vertical axis and slip angle that will prevent progression and reoperation will play an important role in surgical treatment planning. Current evidence supports surgical treatment of degenerative spondylolisthesis. While posterolateral spinal fusion remains the treatment of choice, the use of interbodies and decompressions without fusion may be efficacious in certain populations. However, additional high-quality evidence is needed, especially in newer areas of practice such as minimally invasive techniques and sagittal balance correction.

Basic research toward understanding and treating disc pathology in the spine has utilized numerous animal models, with delivery of small molecules, purified factors, and genes of interest. To date, gene delivery to the rat lumbar spine has only been described utilizing genetically programmed cells in a matrix which has required partial disc excision, and expected limitation of treatment diffusion into the disc.This study was designed to develop and describe a surgical technique for lumbar spine exposure and disc space preparation, and use of a matrix-free method for gene delivery.Naïve or genetically programmed isogeneic bone marrow stromal cells were surgically delivered to adolescent male Lewis rat lumbar discs, and utilizing quantitative biochemical and qualitative immunohistological assessments, the implanted cells were detected 3 days post-procedure.Statistically significant differences were noted for recovery of the β-galactosidase marker gene comparing delivery of naïve or labeled cells (10(5) cells per disc) from the site of implantation, and between delivery of 10(5) or 10(6) labeled cells per disc at the site of implantation and the adjacent vertebral body. Immunohistology confirmed that the β-galactosidase marker was detected in the adjacent vertebra bone in the zone of surgical implantation.The model requires further testing in larger cohorts and with biologically active genes of interest, but the observations from the pilot experiments are very encouraging that this will be a useful comparative model for basic spine research involving gene or cell delivery, or other locally delivered therapies to the intervertebral disc or adjacent vertebral bodies in rats.