![]() This disruption enables circulating immune cells to enter the damaged region with accumulation of macrophages and activation of resident microglia. ![]() Scar formation following injury is driven by a pro-inflammatory immune response partially facilitated by disruption of the blood-brain/spinal cord barrier. Physical properties of the chronic scar and the impacts on the anti-regenerative environment remain particularly understudied. Cellular and biochemical profiles of this scarring response have been widely reported, but a comprehensive understanding of physical properties, such as stiffness/elasticity and underlying tissue architecture, has not been fully realized. Lack of recovery and poor prognosis of SCI is also due in part to the formation of a specialized type of scar tissue that inhibits neurite extension to reconnect lost neural circuits. Prognosis is ultimately tied to the degree of the initial injury broadly categorized as complete (i.e., no function below the point of injury) or incomplete injury (i.e., partial function below the point of injury), and to the degree of secondary injury response. Many cases do not return to pre-injury levels of physiological function, significantly altering the patient’s quality of life. Spinal cord injury (SCI) affects at least a quarter million people in the United States, with a first time occurrence rate of ~17,700 per year. Our results reveal the Young’s modulus of the chronic SCI scar as well as quantification of contributing elastic components that can provide a foundation for future study into their role in tissue repair and regeneration. The key ECM components in the CNS, namely sulfated proteoglycans (sPGs), were significantly downregulated following injury with concomitant upregulation of unsulfated glycosaminoglycans (GAGs) and hyaluronic acid (HA), likely altering the foundational ECM network that contributes to tissue stiffness. Abundant CNS cell types such as astrocytes, oligodendrocytes, and neurons were dysregulated in the scar, while epithelial markers such as vimentin were upregulated. The chronic scar contained cystic cavities dispersed in areas of dense nuclei packing. The spatial Young’s modulus of a chronic (~18-wks, post-injury) hemi-section, including the glial and fibrotic regions, were significantly less than naïve tissue (~ 200 Pa p < 0.0001). This study assessed the glial and fibrotic scar tissue’s Young’s modulus and composition (scar morphometry, cell identity, extracellular matrix (ECM) makeup) that contribute to the tissue’s stiffness. Although the decreased Young’s modulus of surrounding tissue at acute stages post-injury is known, the causation and outcomes at chronic time points remain largely understudied and controversial, which motivates this work. However, altered Young’s modulus of the scar as a readout for potential impeding factors for regeneration are not as well-defined, especially in vivo. Inhibitory cell types and biochemical cues present in the scar have received attention as therapeutic targets to promote regeneration. ![]() Regeneration following spinal cord injury (SCI) is challenging in part due to the modified tissue composition and organization of the resulting glial and fibrotic scar regions. ![]()
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