An overview of tissue engineering approaches for management of spinal cord injuries

Severe spinal cord injury (SCI) leads to devastating neurological deficits and disabilities, which necessitates spending a great deal of health budget for psychological and healthcare problems of these patients and their relatives. This justifies the cost of research into the new modalities for treatment of spinal cord injuries, even in developing countries. Apart from surgical management and nerve grafting, several other approaches have been adopted for management of this condition including pharmacologic and gene therapy, cell therapy, and use of different cell-free or cell-seeded bioscaffolds. In current paper, the recent developments for therapeutic delivery of stem and non-stem cells to the site of injury, and application of cell-free and cell-seeded natural and synthetic scaffolds have been reviewed

Syndromics: A Bioinformatics Approach for Neurotrauma Research

Substantial scientific progress has been made in the past 50 years in delineating many of the biological mechanisms involved in the primary and secondary injuries following trauma to the spinal cord and brain. These advances have highlighted numerous potential therapeutic approaches that may help restore function after injury. Despite these advances, bench-to-bedside translation has remained elusive. Translational testing of novel therapies requires standardized measures of function for comparison across different laboratories, paradigms, and species. Although numerous functional assessments have been developed in animal models, it remains unclear how to best integrate this information to describe the complete translational “syndrome” produced by neurotrauma. The present paper describes a multivariate statistical framework for integrating diverse neurotrauma data and reviews the few papers to date that have taken an information-intensive approach for basic neurotrauma research. We argue that these papers can be described as the seminal works of a new field that we call “syndromics”, which aim to apply informatics tools to disease models to characterize the full set of mechanistic inter-relationships from multi-scale data. In the future, centralized databases of raw neurotrauma data will enable better syndromic approaches and aid future translational research, leading to more efficient testing regimens and more clinically relevant findings

Role of the lesion scar in the response to damage and repair of the central nervous system

Traumatic damage to the central nervous system (CNS) destroys the blood-brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation

Astrocyte scar formation aids central nervous system axon regeneration

Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration

3-D Self-assembled SOI MEMS: Fabrication and Numerical Simulation

The advantages of thin film SOI (Silicon-on-Insulator) technology for MOS circuits compared with thick SOI and bulk silicon MOS techniques are nowadays well known. Among them, we can mention a lower power consumption, better performance on high frequency operation and resistance to irradiation as well as better high temperature characteristics. These advantages in addition to a direct MEMS-IC integration make thin film SOI an attractive process for the manufacture of high quality MEMS and MOS integrated circuits for space applications. In this work, we present tridimensional (3-D) self-assembled multilayered SOI MEMS structures that can be used (but not limited) as flow sensors, thermal actuators and high frequency inductors. These MEMS consist of layers of Si, Si3N4 and Al deposited at different temperatures, and the final shape of the structure can be very different depending on the number, the nature and the thickness of the layers that are deposited. If the system consists only of one layer of Si, the structure remains flat after the release, whereas in the bilayer case (Si and Si3N4) the structure bends up. This is due to the thermal expansion coefficient of the Si3N4, which is higher than the Si one, and therefore the upper part of the structure contracts more than the lower part resulting in a curved shape. The thermal expansion coefficient of the Al being even greater than the Si3N4 one, we would then expect a larger curvature of the structure in the trilayer case, but considering the Al deposition temperature and the geometry we can demonstrate that the shape is rather flat. To obtain a curly shape in the trilayer structure an additional thermal step is needed. It could be a two minutes RTA (Rapid Thermal Annealing) at 600°C or a lower temperature annealing (432°C) but for a longer time (30 min). In order to make quantitative comparisons with numerical simulations, the final shape of these structures was completely characterized using laser interferometry. Numerical simulations were made using the finite element code Oofelie. This code allows us to simulate the fabrication process in a realistic way adding layers one by one and considering the residual stress of the layers already deposited. In this way, an analysis of intermediate stresses in the different layers can be done, and if it is the case, additional residual stresses that do not have a thermal origin can be included. In order to model accurately the 3-D MEMS final shape, which is characterized by large displacements, the code takes into account the geometric nonlinearity. Numerical simulations are in good agreement with experimental data and with available analytical results. Reliable numerical simulations are very helpful to accelerate the MEMS design phase when complex geometries are involved