This work describes for first time the fabrication and characterization of multicomponent interpenetrating networks composed of collagen I, hyaluronic acid, and poly(ethylene glycol) diacrylate for the 3D culture of human neural stem cells, astrocytes, and microglia. The chemical composition of the scaffolds can be modulated while maintaining values of complex moduli within the range of the mechanical performance of brain tissue (≈ 6.9kPa) and having cell viability exceeding 84%. The developed scaffolds are a promising new family of biomaterials that can potentially serve as 3D in vitro models for studying the physiology and physiopathology of the central nervous system.

Hyaluronic acid (HA) is a highly abundant component in the extracellular matrix (ECM) and a fundamental element to the architecture and the physiology of the central nervous system (CNS). Often, HA degradation occurs when an overreactive inflammatory response, derived from tissue trauma or neurodegenerative diseases such as Alzheimer’s, causes the ECM in the CNS to be remodeled. Herein, we studied the effects of HA content as a key regulator of human astrocyte (HAf) reactivity using multicomponent interpenetrating polymer networks (mIPNs) comprised of Collagen I, HA and poly(ethylene glycol) diacrylate. The selected platform facilities the modulation of HA levels independently of matrix rigidity. Total astrocytic processes length, number of endpoints, the expression of the quiescent markers: Aldehyde Dehydrogenase 1 Family Member L1 (ALDH1L1) and Glutamate Aspartate Transporter (GLAST); the reactive markers: Glial Fibrillary Acidic Protein (GFAP) and S100 Calcium-Binding Protein β (S100β); and the inflammatory markers: Inducible Nitric Oxide Synthase (iNOS), Interleukin 1β (IL-1β) and Tumor Necrosis Factor Alpha (TNFα), were assessed. Cumulatively, our results demonstrated that the decrease in HA concentration elicited a reduction in the total length of astrocytic processes and an increase in the expression of HAf reactive and inflammatory markers.

Introduction:The adverse influence of chronic pain on function and psychological health in the general population is well understood. However, the relationship between phantom limb pain (PLP) after limb loss with function and psychological health is less clear. The study purpose was to assess the influences of PLP presence and intensity on function and psychosocial health in individuals with lower-limb loss (LLL).Methods:One hundred two individuals with major LLL completed a study-specific questionnaire on the presence and intensity of their PLP. The Patient-Reported Outcomes Measurement Information System —29 questionnaire was also administered.Results:Of 102 participants, 64% reported PLP, with a mean intensity of 4.8 ± 2.3 out of 10. Individuals with vs. without PLP demonstrated significantly greater sleep disturbances (p = 0.03), whereas the differences in function, fatigue, pain interference, depressive symptoms, anxiety, or ability to participate in social roles and activities were not statistically different between groups (p > 0.05). Of note, mean scores for many of the Patient-Reported Outcomes Measurement Information System—29 short forms among the current sample were similar to the mean of the general population, minimizing the potential clinical impact of PLP on these domains.Conclusions:Our findings indicate a lack of meaningful associations between PLP presence or intensity with function, and psychosocial health among individuals with LLL. These findings conflict with previous research suggesting an adverse relationship between PLP, function, and psychosocial health after limb loss.

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