Speaker
Description
Decellularized brain tissue combined with GelMa as a novel hydrogel emulating extracellular matrix in cerebral organoid-on-chips
Aysel Saskara1, Ozlem Yesil-Celiktas1,2,3
1 Department of Bioengineering, Faculty of Engineering, Ege University, 35100, Bornova, Izmir, Turkey
2 Translational Pulmonary Research Center (EgeSAM), Ege University, 35100, Bornova, Izmir, Turkey
3 ODTÜ MEMS, Ankara, Turkey
*e-mail: ayselsaskara01@gmail.com , ozlem.yesil.celiktas@ege.edu.tr
Introduction
In recent years, advances in biotechnology have significantly contributed to the development of more physiologically relevant in vitro models. Among these innovations, the differentiation of functional cells from induced pluripotent stem cells (iPSCs), the emergence of three-dimensional organoid models, and the design of dynamic organ-on-chip platforms that replicate physiological fluid flow and cellular behavior have garnered remarkable attention. Furthermore, the engineering of tissue-specific biomimetic extracellular matrix (ECM) formulations has further enhanced the fidelity of these models through various strategies. Decellularization is one such approach, involving the removal of cellular and nuclear components from tissues or organs while preserving the native protein and biochemical complexity of the ECM, with the aim of preventing immune responses and replicating natural tissue architecture1. Brain-derived decellularized ECM (dECM) has gained considerable interest in neuroscience due to its ability to more accurately mimic the native brain microenvironment2, thereby providing a favorable environment for organoid survival and maturation. The successful development and long-term maintenance of cerebral organoids critically rely on the ECM, which not only offers mechanical support but also delivers essential biochemical cues that regulate cell adhesion, migration, and differentiation. In the brain, the neuronal ECM creates a highly specialized and dynamic microenvironment that modulates neural-glial interactions, synaptic stability, and plasticity3. In light of these insights, the present study aims to develop a novel brain derived dECM-GelMa biomaterial and integrating it with cerebral organoids for further applications (Fig 1).
Figure 1. Schematic representation.
Methods
Brain tissues were decellularized using novel method. Protein retention and DNA removal efficiency were evaluated through biochemical assays to assess the preservation of ECM integrity. Formulated ECM pre-gel is mixed with GelMa and optimized for further organoid applications.
Results
Biochemical analyses demonstrated that the decellularization process preserved almost 50% of the total brain ECM proteins while removing approximately 80% of the native DNA content.
Discussion
These findings highlight that preserving ECM integrity is crucial for supporting cerebral organoid viability, enhancing neural-glial interactions within the cerebral microenvironment.
Acknowledgement: The funding provided by TUSEB through 40153 project is highly appreciated.
References
Hillebrandt, K. H., Everwien, H., Haep, N., Keshi, E., Pratschke, J., & Sauer, I. M. (2019). Strategies based on organ decellularization and recellularization. Transplant International, 32(6), 571-585
Yaldiz, B., Saglam-Metiner, P., Yesil-Celiktas O. (2022) Decellularized extracellular matrix-based biomaterials for repair and regeneration of central nervous system. Expert Reviews in Molecular Medicine, 23, e25
Saglam-Metiner, P., Yanasik, S., Odabasi, Y.C., Modamio, J., Negwer, M., Biray-Avci, C., Guler, A., Erturk, A., Yildirim, E., Yesil-Celiktas, O. (2024), “ICU patient-on-a-chip: orchestration of mast cells and cerebral organoids in neuroinflammation” Nature – Communications Biology, 7, 1627
Keywords: biomaterial, brain ECM, induced pluripotent stem cell, cerebral organoid
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