Brain injuries caused by an explosive blast or blunt force is typically presumed to associate with mechanical trauma to the brain tissue. Recent findings from our laboratory suggest that shockwaves produced by a blast can generate micron-sized bubbles in the tissue. the collapse of microbubbles (i.e., microcavitation) may induce a mechanical trauma and compromise the integrity of the blood-brain endothelium (BBE). To test our hypothesis, we engineered a BBE model to determine the effect of microbubbles on the structural and functional changes in the BBe. Using monolayers of mouse primary brain microvascular endothelial cells, the permeability coefficient was measured following simulated blast-induced microcavitation. this event down-regulated the expression of tight junction markers, disorganized the cell-cell junction, and increased permeability. Since poloxamers have been shown to rescue damaged cells, the cells were treated with the FDA-approved poloxamer 188 (P188). The results indicate P188 recovered the permeability, restored the tight junctions, and suppressed the expressions of matrix metalloproteinases. the biomimetic interface we developed appears to provide a systematic approach to replicate the structure and function of BBe, determine its alteration in response to traumatic brain injury, and test potential therapeutic treatments to repair the damaged brain endothelium. Traumatic brain injury (TBI) is one of the major causes of emergency visits and hospitalization. In 2010, the Centers for Disease Control reported about 2.5 million emergency department visits, hospitalizations, and deaths here in the United States alone 1. TBIs are also caused by an explosive blast or blunt force to the head especially among those who serve in the U.S. military 2-4. The trauma can lead to endothelial cell detachment, tight junction disruption, and altered blood-brain barrier (BBB) permeability 5,6. One of the unique features of BBB is the regulation of biotransport through a monolayer of brain endothelial cells (BECs). BECs are highly regulated in their structure and function by the tight junction complex that is composed of, among many molecules, zonula occludens (ZO-1) and the occludins family 7,8. Only particles with a molecular mass of less than 500 Daltons can cross the BBB efficiently 9. However, the structural integrity of the BBB can be mechanically and biochemically compromised 10-13 , allowing harmful substances to extravasate into the brain. The leaky brain endothelium, in turn, may lead to secondary brain injury 14-16. Several sophisticated TBI models of explosive blast or blunt force have been studied. However, the potential mechanisms connecting shock wave exposure to the head and to TBI are still not well understood 17. One of the mechanical traumas that have been investigated in our laboratory is the formation of micron-size bubbles in response to shock wave and subsequent collapse of such microbubbles, referred to as microcavitation 18. The collapse of highly pressurized microbubbles is thought to prod...

Traumatic brain injury (TBI) is known to alter the structure and function of the blood–brain barrier (BBB). Blunt force or explosive blast impacting the brain can cause neurological sequelae through the mechanisms that remain yet to be fully elucidated. For example, shockwaves propagating through the brain have been shown to create a mechanical trauma that may disrupt the BBB. Indeed, using tissue engineering approaches, the shockwave-induced mechanical injury has been shown to modulate the organization and permeability of the endothelium tight junctions. Because an injury to the brain endothelium typically induces a high expression of E-selectin, we postulated that upregulation of this protein after an injury can be exploited for diagnosis and potential therapy through targeted nanodelivery to the injured brain endothelium. To test this hypothesis, we engineered poly­(lactic-co-glycolic acid) (PLGA) nanoparticles to encapsulate therapeutic nonbiologics and decorated them with ligands to specifically target the E-selectin. A high level of the conjugated nanoparticles was found inside the injured cells. Repair of the injury site was then quantitatively measured and analyzed. To summarize, exploiting the tunable properties of PLGA, a targeted drug delivery strategy has been developed and validated, which combines the specificity of ligand/receptor interaction with therapeutic reagents. Such a strategy could be used to provide a potential theragnostic approach for the treatment of modulated brain endothelium associated with TBI.

Effect of source separated human urine as buffering agent compared to sodium bicarbonate and water in anaerobic co-digestion of lignocellulosic biomass and poultry feces was evaluated in laboratory scale reactor for 180 days at 37 ± 2 • C. Mean biogas volume ranged from 37 ± 8 to 101 ± 18 mL gVS −1 in the urine buffered reactors which was 1-5 times higher than the bicarbonate and water buffered reactors and the difference was significant at p = 0. 05. Total volatile fatty acids (VFA) concentration ranged between 396 and 1,400 mg L −1 with a pH of 6.9 ± 0.3 and 7.8 ± 0.1, respectively. In contrast, VFA concentration ranged between 386 and 3,109 mg L −1 (pH 7.6 ± 0.2 and 4.8 ± 0.4) in sodium bicarbonate buffered digestate and control (water) respectively. The result indicates buffering capacity of urine on anaerobic co-digestion with positive effect on biogas production. The Archaeal isoprenoids included markers of aceticlastic and hydrogenotrophic methanogens with a relative abundance that ranged between 0.71-18, 3-55, and 2-59 µg g −1 dry matter in the water (control), bicarbonate and urine buffered digestate, respectively. The Archaeal abundance was 1.12 and 6 times higher in the combined female/male urine than the bicarbonate buffered digestate and the control, and the difference was significant at p = 0.05. Overall, this study demonstrates that human urine with no pharmaceutical loadings as a wetting and buffering agent is a promising option for anaerobic co-digestion with competitive edge over sodium bicarbonate on lignocellulosic biomass saccharification for enhanced biogas production. HIGHLIGHTS-Source separated human urine served as buffer in anaerobic co-digestion process.-Combined female/male urine exerted an additive effect on biogas production. -Competitive edge offered by the combined female/male urine over sodium bicarbonate buffer in relation to biogas produced. -Evidence of synergy for enhanced biogas production from high C/N ratio lignocellulosic biomass combined with low C/N ratio poultry feces.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.