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Figure 1. Comparison of 2D cell culture, animal models, and organoids in biomedical research, highlighting their physiological relevance, technical
complexity, and potential applications

to inspire further progress, collaboration, and innovation variability, immunogenicity, and limited controllability hinder
in the global organoid research community. their standardization. In contrast, synthetic biomaterials (e.g.,
Polyethylene Glycol) enable precise modulation of stiffness,
2. Brief history of organoids ligand density, and degradation rates through chemical
The origins of organoid research date back to 1907, initially engineering, offering programmable microenvironments –
based on simple in vitro tissue culture. However, it was not for instance, stiffness-adjusted differentiation of stem cells.
until 2009 that Hans Clevers’ team successfully constructed In self-organization, traditional ECM supports complex
the first intestinal organoid, a breakthrough that laid tissue structures through cell-driven feedback but suffers
the foundation for the rapid development of organoid from compositional complexity. Synthetic materials guide
technology 25,26 (Figure 2). Since then, organoid technology cell alignment through pre-defined architectures with high
has advanced rapidly, with researchers successfully creating reproducibility but lack dynamic responsiveness. Clinically,
organoids of the retina, brain, liver, kidney, skin, and other natural ECM derivatives are applied in tissue repair but face
tissues, significantly advancing the application of in vitro mechanical limitations, while synthetic materials exhibit
biological models. 27-31 innovative potential through multifunctional integration,
though long-term biocompatibility and degradation safety
3. Emerging theories in organoid require validation. To overcome these issues, synthetic
development biomaterials have emerged as promising alternatives.
3.1. Materiobiology-guided organoid construction Engineered hydrogels and custom scaffolds can be precisely
designed to mimic the structural and biochemical features of
Traditional organoid construction relies heavily on Matrigel, native ECM. These materials offer consistent quality, tunable
a complex, animal-derived extracellular matrix (ECM) that mechanical properties, and customizable biochemical cues
supports cell growth and differentiation. However, Matrigel that support cellular behavior and organoid formation. By
32
34
presents several challenges: its composition is variable, its controlling various parameters, such as stiffness, porosity,
animal origin raises ethical concerns, and its mechanical and degradation rates, synthetic matrices enable the creation
properties are limited, hindering its ability to replicate of organoids with improved functional and structural
diverse tissue environments. 33,34 Traditional ECM methods fidelity. 35
rely on natural matrices (e.g., collagen, Matrigel) to regulate
cell differentiation and self-organization through bioactive Materiobiology – the study of how material properties
molecules and dynamic mechanical signals. However, batch influence biological processes – provides a robust theoretical

Volume 1 Issue 1 (2025) 3 doi: 10.36922/OR025040007