Tissue-inspired design of a PEG-based Brain ECM hydrogel
Year: 2018
Type: article
Abstract: Event Abstract Back to Event Tissue-inspired design of a PEG-based Brain ECM hydrogel Sualyneth Galarza1 and Shelly R. Peyton1* 1 Department of Chemical engineering, University of Massachusetts, United States The extracellular matrix (ECM) has been identified as a key mediator of cell response and disease progression. To understand this effect, 3-dimensional in vitro models have been designed to represent matrix-mimicking biomaterials as seen in vivo. Brain ECM in vitro models derived from tissue, such as decellularized scaffolds, and tissue slices, mimic some aspects of brain architecture but are too complex to pinpoint how individual ECM-drivers affect cell behavior. Synthetic hydrogels, in contrast, have the potential to provide control over finite variables like stiffness and ligand presentation, but tend to oversimplify the complex array of proteins present in real tissue. To augment these efforts, we have designed a synthetic hydrogel that captures a brain-specific adhesive and degradable ECM alongside the appropriate viscoelasticity. Via in-house proteomics and histology-based bioinformatics, we screened the human cortex for ECM features that could be incorporated into a PEG-based hydrogel to represent the biochemical and physical properties. To allow for cell adhesion and hydrogel degradation, we filtered proteins with integrin-binding and enzyme cleavage capabilities. These sites are presented as peptides synthesized via solid phase peptide synthesis and incorporated into the hydrogel through Michael type addition. We assessed the mechanical properties of porcine brain and tuned our hydrogel to the same modulus. A 2D competitive assay validated the affinity of cell adhesion to individual integrin-peptides. To assess degradation, human astrocytes were cultured in the 3D hydrogel with integrin-binding and degradable-peptides where cells elongated their processes significantly more than PEG alone. Given that a major challenge in the culture of astrocytes in vitro is their susceptibility to become reactive we quantified activation levels via GFAP where astrocytes remained quiescent in the brain gel compared to activated cells in 3D collagen. Future work will explore the expression of cortex-specific markers in brain gel cultured astrocytes. Keywords: Hydrogel, Extracellular Matrix (ECM), Brain, in vitro, Astrocytes Conference: National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) 45th Annual Conference , Orlando, Florida, United States, 17 Sep - 20 Sep, 2018. Presentation Type: Oral Presentation Topic: Polymer Science and Engineering Citation: Galarza S and Peyton SR (2019). Tissue-inspired design of a PEG-based Brain ECM hydrogel. Front. Chem. Conference Abstract: National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) 45th Annual Conference . doi: 10.3389/conf.fchem.2018.01.00024 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Oct 2018; Published Online: 17 Jan 2019. * Correspondence: PhD. Shelly R Peyton, Department of Chemical engineering, University of Massachusetts, Amherst, Massachusetts, 01003-9303, United States, [email protected] Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sualyneth Galarza Shelly R Peyton Google Sualyneth Galarza Shelly R Peyton Google Scholar Sualyneth Galarza Shelly R Peyton PubMed Sualyneth Galarza Shelly R Peyton Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.
Source: Frontiers in Chemistry
Authors: Sualyneth Galarza, Shelly Peyton
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W2910017411