Chitosan scaffolds appear to be suitable for a variety of tissue engineering applications. This study addressed the biocompatibility of chitosan in a mouse implantation model. Porous chitosan scaffolds were implanted in mice, and animals were sacrificed after 1, 2, 4, 8, or 12 weeks. Macroscopic inspection of the implantation site revealed no pathological inflammatory responses. Histological assessment indicated marked neutrophil accumulation within the implant, which resolved with increasing implantation time. Gram staining and limulus assays revealed no evidence of infection or endotoxin. Collagen was observed within the chitosan pore spaces, indicating that connective tissue matrix was deposited within the implant. Angiogenic activity associated with the external implant surface was also observed. Cellular immune responses were determined by lymphocyte proliferation assays, and antibody responses were measured using ELISA techniques. These assays indicated a very low incidence of chitosan-specific reactions. Although there was a large migration of neutrophils into the implantation area, there were minimal signs of any inflammatory reaction to the material itself. This preliminary study demonstrates that chitosan has a high degree of biocompatibility in this animal model. Overall, the findings suggest that chitosan may be suitable for the development of implantable materials.

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The current study used a rat model to investigate the underlying mechanisms of blast-induced tinnitus, hearing loss, and associated traumatic brain injury (TBI). Seven rats were used to evaluate behavioral evidence of tinnitus and hearing loss, and TBI using magnetic resonance imaging following a single 10-msec blast at 14 psi or 194 dB sound pressure level (SPL). The results demonstrated that the blast exposure induced early onset of tinnitus and central hearing impairment at a broad frequency range. The induced tinnitus and central hearing impairment tended to shift towards high frequencies over time. Hearing threshold measured with auditory brainstem responses also showed an immediate elevation followed by recovery on day 14, coinciding with behaviorally-measured results. Diffusion tensor magnetic resonance imaging results demonstrated significant damage and compensatory plastic changes to certain auditory brain regions, with the majority of changes occurring in the inferior colliculus and medial geniculate body. No significant microstructural changes found in the corpus callosum indicates that the currently adopted blast exposure mainly exerts effects through the auditory pathways rather than through direct impact onto the brain parenchyma. The results showed that this animal model is appropriate for investigation of the mechanisms underlying blast-induced tinnitus, hearing loss, and related TBI. Continued investigation along these lines will help identify pathology with injury/recovery patterns, aiding development of effective treatment strategies.

The desire to make microfluidic technology more accessible to the biological research community has led to the notion of "modular microfluidics", where users can build a fluidic system using a toolkit of building blocks. This paper applies a modular approach for performing droplet-based screening, including the four integral steps of library generation, storage, mixing, and optical interrogation. Commercially available cross-junctions are used for drop generation, flexible capillary tubing for storage, and tee-junctions for serial mixing. Optical interrogation of the drops is achieved using fiber-optic detection modules which can be incorporated inline at one or more points in the system. Modularity enables the user to hand-assemble systems for functional assays or applications. Three examples are shown: (1) a "mix and read" assay commonly used in high throughput screening (HTS); (2) generation of chemically distinct droplets using microfractionation in droplets (microFD); and (3) in situ encapsulation and culture of eukaryotes. Using components with IDs ranging from 150 microm to 1.5 mm, this approach can accommodate drop assays with volumes ranging from 2 nL to 2 microL, and storage densities ranging from 300 to 3000 drops per metre tubing. Generation rates are up to 200 drops per second and merging rates are up to 10 drops per second. The impact of length scale, carrier fluid viscosity, and flow rates on system performance is considered theoretically and illustratively using 2D CFD simulations. Due to its flexibility, the widespread availability of components, and some favorable material properties compared to PDMS, this approach can be a useful part of a researcher's toolkit for prototyping droplet-based assays.

Identifying the level of overpressure required to create physiological deficits is vital to advance prevention, diagnostic, and treatment strategies for individuals exposed to blasts. In this study, a rodent model of primary blast neurotrauma was employed to determine the pressure at which acute neurological alterations occurred. Rats were exposed to a single low intensity shock wave at a pressure of 0, 97, 117, or 153 kPa. Following exposure, rats were assessed for acute cognitive alterations using the Morris water maze and motor dysfunction using the horizontal ladder test. Subsequently, histological analyses of three brain regions (primary motor cortex, the hippocampal dentate gyrus region, and the posteromedial cortical amygdala) were conducted. Histological parameters included measuring the levels of glial fibrillary acidic protein (GFAP) to identify astrocyte activation, cleaved caspase-3 for early apoptosis identification and Fluoro-Jade B (FJB) which labels degenerating neurons within the brain tissue. The results demonstrated that an exposure to a single 117 kPa shock wave revealed a significant change in overall neurological deficits when compared to controls and the other pressures. The animals showed significant alterations in water maze parameters and a histological increase in the number of GFAP, caspase-3, and FJB-positive cells. It is suggested that when exposed to a low level shock wave, there may be a biomechanical response elicited by a specific pressure range which can cause low level neurological deficits within the rat. These data indicate that neurotrauma induced from a shock wave may lead to cognitive deficits in short-term learning and memory of rats. Additional histological evidence supports significant and diffuse glial activation and cellular damage. Further investigation into the biomechanical aspects of shock wave exposure is required to elucidate this pressure range-specific phenomenon.

Significance We have developed hemostatic nanoparticles that reduce bleeding and increase survival in both the short term and long term following the complex injuries sustained during blast trauma. This treatment has the potential to be deployed by first responders to save lives.

Traumatic brain injuries (TBI) caused by improvised explosive devices (IEDs) affect a significant percentage of surviving soldiers wounded in Iraq and Afghanistan. The extent of a blast TBI, especially initially, is difficult to diagnose, as internal injuries are frequently unrecognized and therefore underestimated, yet problems develop over time. Therefore it is paramount to resolve the physical mechanisms by which critical stresses are inflicted on brain tissue from blast wave encounters with the head. This study recorded direct pressure within the brains of male Sprague-Dawley rats during exposure to blast. The goal was to understand pressure wave dynamics through the brain. In addition, we optimized in vivo methods to ensure accurate measurement of intracranial pressure (ICP). Our results demonstrate that proper sealing techniques lead to a significant increase in ICP values, compared to the outside overpressure generated by the blast. Further, the values seem to have a direct relation to a rat's size and age: heavier, older rats had the highest ICP readings. These findings suggest that a global flexure of the skull by the transient shockwave is an important mechanism of pressure transmission inside the brain.