Historically, glial cells have been recognized as a structural component of the brain. However, it has become clear that glial cells are intimately involved in the complexities of neural networks and memory formations. Astrocytes, microglia, and oligodendrocytes have dynamic responsibilities which substantially impact neuronal function and activities. Moreover, the importance of glia following brain injury has come to the forefront in discussions to improve axonal regeneration and functional recovery. The numerous activities of glia following injury can either promote recovery or underlie the pathobiology of memory deficits. This review outlines the pathological states of glial cells which evolve from their positive supporting roles to those which disrupt synaptic function and neuroplasticity following injury. Evidence suggests that glial cells interact extensively with neurons both chemically and physically, reinforcing their role as pivotal for higher brain functions such as learning and memory. Collectively, this mini review surveys investigations of how glial dysfunction following brain injury can alter mechanisms of synaptic plasticity and how this may be related to an increased risk for persistent memory deficits. We also include recent findings, that demonstrate new molecular avenues for clinical biomarker discovery.

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Hyaluronic acid (HA) is an abundant extracellular matrix (ECM) component in soft tissues throughout the body and has found wide adoption in tissue engineering. This study focuses on the optimization of methacrylated HA (MeHA) for three-dimensional (3D) bioprinting to create in vitro test beds that incorporate regeneration-promoting growth factors in neural repair processes. To evaluate MeHA as a potential bioink, rheological studies were performed with PC-12 cells to demonstrate shear thinning properties maintained when printing with and without cells. Next, an extrusion-based Cellink BIO X 3D printer was used to bioprint various MeHA solutions combined with collagen-I to determine which formulation was the most optimal for creating 3D features. Results indicated that MeHA (10 mg/mL) with collagen-I (3 mg/mL) was most suitable. As Schwann cells (SCs) are a critical component of neural repair and regeneration, SC adhesion assessment via integrin β1 immunostaining indicated that the bioink candidate adequately supported SC adhesion and migration when compared to Col-I, a highly cell-adhesive ECM component. MeHA/collagen-I bioink was adapted for neural specific applications by printing with the neural growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). These test beds were conducive for SC infiltration and presented differential migration responses. Finally, a two-chamber in vitro test bed design was created to study competitive biochemical cues. Dorsal root ganglia were seeded in test beds and demonstrated directional neurite extension (measured by β-III tubulin and GAP43 immunostaining) in response to NGF and GDNF. Overall, the selected MeHA/collagen-I bioink was bioprintable, improved cell viability compared to molded controls, and was conducive for cell adhesion, growth factor sequestration, and neural cell infiltration. MeHA is a suitable bioink candidate for extrusion-based bioprinting and will be useful in future development of spatially complex test beds to advance in vitro models as an alternative to common in vivo tests for neural repair applications.

Decellularized tissues hold great potential for both regenerative medicine and disease modeling applications. The acellular extracellular matrix (ECM)-enriched scaffolds can be recellularized with patient-derived cells prior to transplantation, or digested...