Bioactive and chemically defined hydrogels with tunable stiffness guide cerebral organoid formation and modulate multi-omics plasticity in cerebral organoids.

Autor: Isik M; Stem Cell Research Lab, Department of Chemistry, Faculty of Science, Ankara University, Ankara 06560, Turkey., Okesola BO; School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2UH, UK., Eylem CC; Analytical Chemistry Division, Faculty of Pharmacy, Hacettepe University, Ankara 06230, Turkey., Kocak E; Division of Analytical Chemistry, Faculty of Gulhane Pharmacy, Health Science University, Ankara 06018, Turkey., Nemutlu E; Analytical Chemistry Division, Faculty of Pharmacy, Hacettepe University, Ankara 06230, Turkey; Bioanalytic and Omics Laboratory, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey., D'Este M; AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz 7270, Switzerland., Mata A; School of Pharmacy University of Nottingham, University Park, Nottingham NG7 2RD, UK; Department of Chemical and Environmental Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK., Derkus B; Stem Cell Research Lab, Department of Chemistry, Faculty of Science, Ankara University, Ankara 06560, Turkey. Electronic address: bderkus@ankara.edu.tr.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2023 Nov; Vol. 171, pp. 223-238. Date of Electronic Publication: 2023 Oct 02.
DOI: 10.1016/j.actbio.2023.09.040
Abstrakt: Organoids are an emerging technology with great potential in human disease modelling, drug development, diagnosis, tissue engineering, and regenerative medicine. Organoids as 3D-tissue culture systems have gained special attention in the past decades due to their ability to faithfully recapitulate the complexity of organ-specific tissues. Despite considerable successes in culturing physiologically relevant organoids, their real-life applications are currently limited by challenges such as scarcity of an appropriate biomimetic matrix. Peptide amphiphiles (PAs) due to their well-defined chemistry, tunable bioactivity, and extracellular matrix (ECM)-like nanofibrous architecture represent an attractive material scaffold for organoids development. Using cerebral organoids (COs) as exemplar, we demonstrate the possibility to create bio-instructive hydrogels with tunable stiffness ranging from 0.69 kPa to 2.24 kPa to culture and induce COs growth. We used orthogonal chemistry involving oxidative coupling and supramolecular interactions to create two-component hydrogels integrating the bio-instructive activity and ECM-like nanofibrous architecture of a laminin-mimetic PAs (IKVAV-PA) and tunable crosslinking density of hyaluronic acid functionalized with tyramine (HA-Try). Multi-omics technology including transcriptomics, proteomics, and metabolomics reveals the induction and growth of COs in soft HA-Tyr hydrogels containing PA-IKVAV such that the COs display morphology and biomolecular signatures similar to those grown in Matrigel scaffolds. Our materials hold great promise as a safe synthetic ECM for COs induction and growth. Our approach represents a well-defined alternative to animal-derived matrices for the culture of COs and might expand the applicability of organoids in basic and clinical research. STATEMENT OF SIGNIFICANCE: Synthetic bio-instructive materials which display tissue-specific functionality and nanoscale architecture of the native extracellular matrix are attractive matrices for organoids development. These synthetic matrices are chemically defined and animal-free compared to current gold standard matrices such as Matrigel. Here, we developed hydrogel matrices with tunable stiffness, which incorporate laminin-mimetic peptide amphiphiles to grow and expand cerebral organoids. Using multi-omics tools, the present study provides exciting data on the effects of neuro-inductive cues on the biomolecular profiles of brain organoids.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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