Increased phosphorylation of mTOR is involved in remote ischemic preconditioning of hippocampus in mice

Different signaling pathways are involved in tissue protection against ischemia reperfusion (IR) injury, among them mammalian target of rapamycin (mTOR) and related pathways have been examined in many recent studies. Present study evaluated the role of mTOR in remote ischemic preconditioning (RIPC) of hippocampus. Renal ischemia was induced (3 cycles of 5 min occlusion and 5 min reperfusion of unilateral renal artery) 24 h before global brain ischemia (20 min bilateral common carotid artery occlusion). Saline or rapamycin (mTOR inhibitor; 5 mg/kg, i.p.) was injected 30 min before RIPC. mTOR and phosphorylated mTOR (p-mTOR) expression, superoxide dismutase (SOD) activity and retention trial of passive avoidance test were determined 24 h after global ischemia. Apoptosis and neuronal cell density were assessed 72 h after hippocampal ischemia. RIPC decreased apoptosis (p<0.05 vs. IR), improved memory (p<0.05 vs. IR), and augmented p-mTOR expression and SOD activity after hippocampal ischemia (p<0.05 vs. IR). Rapamycin abolished all protective effects of RIPC (p<0.05 vs. RIPC+IR) suggesting a role for mTOR in RIPC induced hippocampal protection. © 2013 Elsevier B.V. All rights reserved

Template‐Enabled Biofabrication of Thick 3D Tissues with Patterned Perfusable Macrochannels

Interconnected pathways in 3D bioartificial organs are essential to retaining cell activity in thick functional 3D tissues. 3D bioprinting methods have been widely explored in biofabrication of functionally patterned tissues; however, these methods are costly and confined to thin tissue layers due to poor control of low-viscosity bioinks. Here, cell-laden hydrogels that could be precisely patterned via water-soluble gelatin templates are constructed by economical extrusion 3D printed plastic templates. Tortuous co-continuous plastic networks, designed based on triply periodic minimal surfaces (TPMS), serve as a sacrificial pattern to shape the secondary sacrificial gelatin templates. These templates are eventually used to form cell-encapsulated gelatin methacryloyl (GelMA) hydrogel scaffolds patterned with the complex interconnected pathways. The proposed fabrication process is compatible with photo-crosslinkable hydrogels wherein prepolymer casting enables incorporation of high cell populations with high viability. The cell-laden hydrogel constructs are characterized by robust mechanical behavior. In vivo studies demonstrate a superior cell ingrowth into the highly permeable constructs compared to the bulk hydrogels. Perfusable complex interconnected networks within cell-encapsulated hydrogels may assist in engineering thick and functional tissue constructs through the permeable internal channels for efficient cellular activities in vivo