Modeling the effects of hyaluronic acid degradation on the regulation of human astrocyte phenotype using multicomponent interpenetrating polymer networks (mIPNs)

Andrea C Jimenez-Vergara,Tyler Cagle,Rachel Van Drunen,Dany J Munoz-Pinto

doi:10.1038/s41598-020-77655-1

Andrea C Jimenez-Vergara, Tyler Cagle + Show 2 more

Open Access

https://doi.org/10.1038/s41598-020-77655-1

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Journal: Scientific Reports	Publication Date: Nov 26, 2020
Citations: 8	License type: open-access

Affiliation: Trinity University

Abstract

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.

Highlights

Astrocytes are integral to the central nervous system (CNS) t issue[1]
To fabricate a 3D in vitro culture model to study the behavior of CNS cells, research efforts have focused on bioinspired hydrogels that recapitulate some of the key biochemical cues for the main extracellular matrix (ECM) constituents in the CNS29,30
The total cell viability for each formulation was estimated by taking the ratio between living cells and total cell count revealed that 24 h post fabrication about 94.0 ± 2.2%, 93.2 ± 1.5% and 94.8 ± 0.7% of cells were alive in the 2 mg/mL, 1 mg/mL and 0 mg/mL hyaluronic acid (HA) multicomponent interpenetrating polymer networks (mIPNs) formulations respectively (Supplementary Fig. 2)

Summary

Introduction

Astrocytes are integral to the central nervous system (CNS) t issue[1]. They provide nutrients to neurons and support neural functions including axonal guidance, synaptic support, and maintenance of the blood brain b arrier[2,3,4,5,6]. To study key characteristics of the function and interactions between astrocytes and ECM components in the CNS, in vitro platforms have typically been established using 2D microenvironments These 2D environments, do not accurately resemble the viscoelastic properties of CNS tissue nor do they capture the 3D cell milieu of native tissue. To fabricate a 3D in vitro culture model to study the behavior of CNS cells, research efforts have focused on bioinspired hydrogels that recapitulate some of the key biochemical cues for the main ECM constituents in the CNS29,30. Both natural and synthetic materials have been utilized to mimic the 3D landscape of CNS tissue. Natural polymers alone are not sufficient to withstand the physiological pressure induced by cellular proliferation, spreading, and cell-mediated degradation[35,36]

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