Skeletal myotube formation enhanced by electrospun polyurethane carbon nanotube scaffolds

Sirinrath Sirivisoot, Benjamin S Harrison Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC, USA Background: This study examined the effects of electrically conductive materials made from electrospun single- or multiwalled carbon nanotubes with polyurethane to promote myoblast differentiation into myotubes in the presence and absence of electrical stimulation. Methods and results: After electrical stimulation, the number of multinucleated myotubes on the electrospun polyurethane carbon nanotube scaffolds was significantly larger than that on nonconductive electrospun polyurethane scaffolds (5% and 10% w/v polyurethane). In the absence of electrical stimulation, myoblasts also differentiated on the electrospun polyurethane carbon nanotube scaffolds, as evidenced by expression of Myf-5 and myosin heavy chains. The myotube number and length were significantly greater on the electrospun carbon nanotubes with 10% w/v polyurethane than on those with 5% w/v polyurethane. The results suggest that, in the absence of electrical stimulation, skeletal myotube formation is dependent on the morphology of the electrospun scaffolds, while with electrical stimulation it is dependent on the electrical conductivity of the scaffolds. Conclusion: This study indicates that electrospun polyurethane carbon nanotubes can be used to modulate skeletal myotube formation with or without application of electrical stimulation. Keywords: myoblasts, electrical field, single-walled, multiwalled, carbon nanotubes, nanocomposites, musculoskeletal, tissue engineerin

SpaceOAR to improve dosimetric outcomes for monotherapy high-dose-rate prostate implantation in a patient with ulcerative colitis.

High-dose-rate (HDR) brachytherapy is an attractive option for patients receiving definitive radiation therapy for prostate cancer with decreased overall dose to the pelvis. However, ulcerative colitis increases rectal toxicity risk and may be a contraindication. A synthetic hydrogel, SpaceOAR (Augmentix Inc., Waltham, MA, USA), can facilitate the use of HDR brachytherapy for patients where rectal toxicity is a limiting factor. SpaceOAR gel (13.19 cc) was utilized in a monotherapy HDR prostate treatment with Ir-192 under transrectal ultrasound guidance, with the intention of decreasing rectal dose. SpaceOAR gel was inserted transperineally into the patient 18 days prior to the procedure. The HDR brachytherapy procedure was tolerated without incident. All planning constraints were met, and the following dosimetry was achieved: Prostate – V100% = 97.3%, V150% = 35%, V200% = 14.5%; Urethra – V118% = 0%; Rectum – D2 cc = 51.6%, V75% = 0 cc. The rectum-catheter spacing was on average between 6-8 mm. Average spacing for our 10 most recent patients without SpaceOAR was 3 mm. SpaceOAR did not hinder or distort ultrasound imaging or increase treatment time. SpaceOAR successfully increases catheter-rectal wall spacing and decreases rectal dose due to improved planning capabilities, while decreasing the likelihood of rectal perforation. One application of this tool is presented to mitigate potential toxicities associated with ulcerative colitis. At five months, one week, and one day follow-up, the patient reported no bowel issues following HDR brachytherapy. © 2018 Termedia Publishing House Ltd. All Rights Reserved

Achieving Acetylcholine Receptor Clustering in Tissue-Engineered Skeletal Muscle Constructs In vitro through a Materials-Directed Agrin Delivery Approach

Volumetric muscle loss (VML) can result from trauma, infection, congenital anomalies, or surgery, and produce permanent functional and cosmetic deficits. There are no effective treatment options for VML injuries, and recent advances toward development of muscle constructs lack the ability to achieve innervation necessary for long-term function. We sought to develop a proof-of-concept biomaterial construct that could achieve acetylcholine receptor (AChR) clustering on muscle-derived cells (MDCs) in vitro. The approach consisted of the presentation of neural (Z+) agrin from the surface of microspheres embedded with a fibrin hydrogel to muscle cells (C2C12 cell line or primary rat MDCs). AChR clustering was spatially restricted to areas of cell (C2C12)-microsphere contact when the microspheres were delivered in suspension or when they were incorporated into a thin (2D) fibrin hydrogel. AChR clusters were observed from 16 to 72 h after treatment when Z+ agrin was adsorbed to the microspheres, and for greater than 120 h when agrin was covalently coupled to the microspheres. Little to no AChR clustering was observed when agrin-coated microspheres were delivered from specially designed 3D fibrin constructs. However, cyclic stretch in combination with agrin-presenting microspheres led to dramatic enhancement of AChR clustering in cells cultured on these 3D fibrin constructs, suggesting a synergistic effect between mechanical strain and agrin stimulation of AChR clustering in vitro. These studies highlight a strategy for maintaining a physiological phenotype characterized by motor endplates of muscle cells used in tissue engineering strategies for muscle regeneration. As such, these observations may provide an important first step toward improving function of tissue-engineered constructs for treatment of VML injuries

The Ursinus Weekly, January 26, 1914

Library notes • Lecture on Christianity • Will hold Valentine fete • Platform meetings • Examinations over: let us celebrate • Youth\u27s progress • Operated upon for appendicitis • Christian organizations • Final call • Modern philanthropy • An economic aspect of war • Shakespeare\u27s attitude toward history • Ch.-Bi\u27s. lose out to H.-P.\u27s • Lecturer coming • Society noteshttps://digitalcommons.ursinus.edu/weekly/2685/thumbnail.jp

Stakeholder-Driven Design Evolution of the Leveraged Freedom Chair Developing World Wheelchair

The Leveraged Freedom Chair (LFC) is a low-cost, all-terrain, variable mechanical advantage, lever-propelled wheelchair designed for use in developing countries. The user effectively changes gear by shifting his hands along the levers; grasping near the ends increases torque delivered to the drive-train, while grasping near the pivots enables a larger angular displacement with every stroke, which increases angular velocity in the drivetrain and makes the chair go faster. This paper chronicles the design evolution of the LFC through three user trials in East Africa, Guatemala, and India. Feedback from test subjects was used to refine the chair between trials, resulting in a device 9.1 kg (20 lbs) lighter, 8.9 cm (3.5 in) narrower, and with a center of gravity 12.7 cm (5 in) lower than the first iteration. Survey data substantiated increases in performance after successive iterations. Quantitative biomechanical performance data were also measured during the Guatemala and India trials, which showed the LFC to be 76 percent faster and 41 percent more efficient during a common daily commute and able to produce 51 percent higher peak propulsion force compared to conventional, pushrim-propelled wheelchairs

Induction of miR-155 after Brain Injury Promotes Type 1 Interferon and has a Neuroprotective Effect.

Traumatic brain injury (TBI) produces profound and lasting neuroinflammation that has both beneficial and detrimental effects. Recent evidence has implicated microRNAs (miRNAs) in the regulation of inflammation both in the periphery and the CNS. We examined the expression of inflammation associated miRNAs in the context of TBI using a mouse controlled cortical impact (CCI) model and found increased levels of miR-21, miR-223 and miR-155 in the hippocampus after CCI. The expression of miR-155 was elevated 9-fold after CCI, an increase confirmed by in situ hybridization (ISH). Interestingly, expression of miR-155 was largely found in neuronal nuclei as evidenced by co-localization with DAPI in MAP2 positive neurons. In miR-155 knock out (KO) mice expression of type I interferons IFNα and IFNβ, as well as IFN regulatory factor 1 and IFN-induced chemokine CXCL10 was decreased after TBI relative to wild type (WT) mice. Unexpectedly, miR-155 KO mice had increased levels of microglial marker Iba1 and increased neuronal degeneration as measured by fluoro-jade C (FJC) staining, suggesting a neuroprotective role for miR-155 in the context of TBI. This work demonstrates a role for miR-155 in regulation of the IFN response and neurodegeneration in the aftermath of TBI. While the presence of neuronal nuclear miRNAs has been described previously, their importance in disease states is relatively unknown. Here, we show evidence of dynamic regulation and pathological function of a nuclear miRNA in TBI

Risk Factors for Pediatric Invasive Group A Streptococcal Disease

Invasive group A Streptococcus (GAS) infections can be fatal and can occur in healthy children. A case-control study identified factors associated with pediatric disease. Case-patients were identified when Streptococcus pyogenes was isolated from a normally sterile site, and matched controls (≥2) were identified by using sequential-digit dialing. All participants were noninstitutionalized surveillance-area residents <18 years of age. Conditional regression identified factors associated with invasive disease: other children living in the home (odds ratio [OR] = 16.85, p = 0.0002) and new use of nonsteroidal antiinflammatory drugs (OR = 10.64, p = 0.005) were associated with increased risk. More rooms in the home (OR = 0.67, p = 0.03) and household member(s) with runny nose (OR = 0.09, p = 0.002) were associated with decreased risk. Among children, household-level characteristics that influence exposure to GAS most affect development of invasive disease

Traumatic brain injury increases levels of miR-21 in extracellular vesicles: implications for neuroinflammation

Traumatic brain injury (TBI) is an important health concern and effective treatment strategies remain elusive. Understanding the complex multicellular response to TBI may provide new avenues for intervention. In the context of TBI, cell–cell communication is critical. One relatively unexplored form of cell–cell communication in TBI is extracellular vesicles (EVs). These membrane‐bound vesicles can carry many different types of cargo between cells. Recently, miRNA in EVs have been shown to mediate neuroinflammation and neuronal injury. To explore the role of EV‐associated miRNA in TBI, we isolated EVs from the brain of injured mice and controls, purified RNA from brain EVs, and performed miRNA sequencing. We found that the expression of miR‐212 decreased, while miR‐21, miR‐146, miR‐7a, and miR‐7b were significantly increased with injury, with miR‐21 showing the largest change between conditions. The expression of miR‐21 in the brain was primarily localized to neurons near the lesion site. Interestingly, adjacent to these miR‐21‐expressing neurons were activated microglia. The concurrent increase in miR‐21 in EVs with the elevation of miR‐21 in neurons, suggests that miR‐21 is secreted from neurons as potential EV cargo. Thus, this study reveals a new potential mechanism of cell–cell communication not previously described in TBI