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Glycocalyx (GCX) is a carbohydrate-rich structure that coats the surface of endothelial cells (ECs) and lines the blood vessel lumen. Mechanical perturbations in the vascular environment, such as blood vessel stiffness, can be transduced and sent to ECs through mechanosensors such as GCX. Adverse stiffness alters GCX-mediated mechanotransduction and leads to EC dysfunction and eventually atherosclerotic cardiovascular diseases. To understand GCX-regulated mechanotransduction events, anin vitromodel emulatingin vivovessel conditions is needed. To this end, we investigated the impact of matrix chemical and mechanical properties on GCX expression via fabricating a tunable non-swelling matrix based on the collagen-derived polypeptide, gelatin. To study the effect of matrix composition, we conducted a comparative analysis of GCX expression using different concentrations (60–25,000 μg/mL) of gelatin and gelatin methacrylate (GelMA) in comparison to fibronectin (60 μg/mL), a standard coating material for GCX-related studies. Using immunocytochemistry analysis, we showed for the first time that different substrate compositions and concentrations altered the overall GCX expression on human umbilical vein ECs (HUVECs). Subsequently, GelMA hydrogels were fabricated with stiffnesses of 2.5 and 5 kPa, representing healthy vessel tissues, and 10 kPa, corresponding to diseased vessel tissues. Immunocytochemistry analysis showed that on hydrogels with different levels of stiffness, the GCX expression in HUVECs remained unchanged, while its major polysaccharide components exhibited dysregulation in distinct patterns. For example, there was a significant decrease in heparan sulfate expression on pathological substrates (10 kPa), while sialic acid expression increased with increased matrix stiffness. This study suggests the specific mechanisms through which GCX may influence ECs in modulating barrier function, immune cell adhesion, and mechanotransduction function under distinct chemical and mechanical conditions of both healthy and diseased substrates. 

Neural stem cells have attracted attention in recent years to treat neurodegeneration. There are two neurogenic regions in the brain where neural stem cells reside, one of which is called the subventricular zone (SVZ). The SVZ niche is a complicated microenvironment providing cues to regulate self-renewal and differentiation while maintaining the neural stem cell’s pool. Many scientists have spent years understanding the cellular and structural characteristics of the SVZ niche, both in homeostasis and pathological conditions. On the other hand, engineers focus primarily on designing platforms using the knowledge they acquire to understand the effect of individual factors on neural stem cell fate decisions. This review provides a general overview of what we know about the components of the SVZ niche, including the residing cells, extracellular matrix (ECM), growth factors, their interactions, and SVZ niche changes during aging and neurodegenerative diseases. Furthermore, an overview will be given on the biomaterials used to mimic neurogenic niche microenvironments and the design considerations applied to add bioactivity while meeting the structural requirements. Finally, it will discuss the potential gaps in mimicking the microenvironment.