Highly Adhesive Antimicrobial Coatings for External Fixation Devices.

Pin site infections arise from the use of percutaneous pinning techniques (as seen in skeletal traction, percutaneous fracture pinning, and external fixation for fracture stabilization or complex deformity reconstruction). These sites are niduses for infection because the skin barrier is disrupted, allowing for bacteria to enter a previously privileged area. After external fixation, the rate of pin site infections can reach up to 100%. Following pin site infection, the pin may loosen, causing increased pain (increasing narcotic usage) and decreasing the fixation of the fracture or deformity correction construct. More serious complications include osteomyelitis and deep tissue infections. Due to the morbidity and costs associated with its sequelae, strategies to reduce pin site infections are vital. Current strategies for preventing implant-associated infections include coatings with antibiotics, antimicrobial polymers and peptides, silver, and other antiseptics like chlorhexidine and silver-sulfadiazine. Problems facing the development of antimicrobial coatings on orthopedic implants and, specifically, on pins known as Kirschner wires (or K-wires) include poor adhesion of the drug-eluting layer, which is easily removed by shear forces during the implantation. Development of highly adhesive drug-eluting coatings could therefore lead to improved antimicrobial efficacy of these devices and ultimately reduce the burden of pin site infections. In response to this need, we developed two types of gel coatings: synthetic poly-glycidyl methacrylate-based and natural-chitosan-based. Upon drying, these gel coatings showed strong adhesion to pins and remained undamaged after the application of strong shear forces. We also demonstrated that antibiotics can be incorporated into these gels, and a K-wire with such a coating retained antimicrobial efficacy after drilling into and removal from a bone. Such a coating could be invaluable for K-wires and other orthopedic implants that experience strong shear forces during their implantation.

Protective Effects of Estrogen via Nanoparticle Delivery to Attenuate Myelin Loss and Neuronal Death after Spinal Cord Injury.

Spinal cord injury (SCI) is associated with devastating neurological deficits affecting more than 11,000 Americans each year. Although several therapeutic agents have been proposed and tested, no FDA-approved pharmacotherapy is available for SCI treatment. We have recently demonstrated that estrogen (E2) acts as an antioxidant and anti-inflammatory agent, attenuating gliosis in SCI. We have also demonstrated that nanoparticle-mediated focal delivery of E2 to the injured spinal cord decreases lesion size, reactive gliosis, and glial scar formation. The current study tested in vitro effects of E2 on reactive oxygen species (ROS) and calpain activity in microglia, astroglia, macrophages, and fibroblasts, which are believed to participate in the inflammatory events and glial scar formation after SCI. E2 treatment decreased ROS production and calpain activity in these glial cells, macrophages, and fibroblast cells in vitro. This study also tested the efficacy of fast- and slow-release nanoparticle-E2 constructs in a rat model of SCI. Focal delivery of E2 via nanoparticles increased tissue distribution of E2 over time, attenuated cell death, and improved myelin preservation in injured spinal cord. Specifically, the fast-release nanoparticle-E2 construct reduced the Bax/Bcl-2 ratio in injured spinal cord tissues, and the slow-release nanoparticle-E2 construct prevented gliosis and penumbral demyelination distal to the lesion site. These data suggest this novel E2 delivery strategy to the lesion site may decrease inflammation and improve functional outcomes following SCI.

Nanoparticle-Based Estrogen Delivery to Spinal Cord Injury Site Reduces Local Parenchymal Destruction and Improves Functional Recovery.

Spinal cord injury (SCI) patients sustain significant functional impairments; this is causally related to restricted neuronal regeneration after injury. The ensuing reactive gliosis, inflammatory cascade, and glial scar formation impede axonal regrowth. Although systemic anti-inflammatory agents (steroids) have been previously administered to counteract this, no current therapeutic is approved for post-injury neuronal regeneration, in part because of related side effects. Likewise, therapeutic systemic estrogen levels exhibit neuroprotective properties, but dose-dependent side effects are prohibitive. The current study thus uses low-dose estrogen delivery to the spinal cord injury (SCI) site using an agarose gel patch embedded with estrogen-loaded nanoparticles. Compared to controls, spinal cords from rodents treated with nanoparticle site-directed estrogen demonstrated significantly decreased post-injury lesion size, reactive gliosis, and glial scar formation. However, axonal regeneration, vascular endothelial growth factor production, and glial-cell-derived neurotrophic factor levels were increased with estrogen administration. Concomitantly improved locomotor and bladder functional recovery were observed with estrogen administration after injury. Therefore, low-dose site-directed estrogen may provide a future approach for enhanced neuronal repair and functional recovery in SCI patients.

Nanoceria: Metabolic interactions and delivery through PLGA-encapsulation.

Cerium oxide nanoparticles (nanoceria) have recyclable antioxidative activity. It has numerous potential applications in biomedical engineering, such as mitigating damage from burns, radiation, and bacterial infection. This mitigating activity is analogous to that property of metabolic enzymes such as superoxide dismutase (SOD) and catalase - scavengers of reactive oxygen species (ROS). Therefore, nanoceria can protect cells from environmental oxidative stress. This therapeutic effect prompted studies of nanoceria and metabolic enzymes as a combination therapy. The activity and structure of SOD, catalase, and lysozyme were examined in the presence of nanoceria. A complementary relationship between SOD and nanoceria motivated the present work, in which we explored a method for simultaneous delivery of SOD and nanoceria. The biocompatibility and tunable degradation of poly(lactic-co-glycolic acid) (PLGA) made it a candidate material for encapsulating both nanoceria and SOD. Cellular uptake studies were conducted along with a cytotoxicity assay. The antioxidative properties of PLGA-nanoceria-SOD particles were verified by adding H2O2 to cell culture and imaging with fluorescent markers of oxidative stress. Our results suggest that PLGA is a suitable encapsulating carrier for simultaneous delivering nanoceria and SOD together, and that this combination effectively reduces oxidative stress in vitro.

Hemorrhoidal artery ligation with Doppler guidance vs digital guidance for grade II-III hemorrhoidal disease treatment: Study protocol clinical trial (SPIRIT Compliant).

INTRODUCTION: Hemorrhoidal artery ligation (HAL) with Doppler guidance and suture fixation of hemorrhoidal nodes (RAR) is a popular minimally invasive technique for hemorrhoidal disease (HD) treatment which uses an ultrasound probe to detect hemorrhoidal arteries for further ligation. We hypothesized that ultrasound guidance has no advantages over manual hemorrhoidal arteries detection for HD treatment.The aim is to compare the results of HAL-RAR procedure in patients with stage II-III HD with Doppler and manual HA detection.In this ongoing randomized, controlled, single center clinical study 204 patients randomly divides into group A (HAL-RAR with Doppler US navigation) and group B (HAL with manual HA detection and mucopexy) are planned to be included. The primary endpoint was recurrence of any symptoms of HD; secondary endpoints were pain syndrome severity, treatment satisfaction (1 to 5 points), and need for the drug therapy in 30 days and 8 weeks after surgery. CONCLUSION: Ultrasound guidance technology of HAL with mucopexy could have the same efficacy the manual HA detection regarding the HD treatment effectiveness and patient satisfaction.