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Engineered materials for organoid systems.
Literature Information
| DOI | 10.1038/s41578-019-0129-9 |
|---|---|
| PMID | 33552558 |
| Journal | Nature reviews. Materials |
| Impact Factor | 86.2 |
| JCR Quartile | Q1 |
| Publication Year | 2019 |
| Times Cited | 155 |
| Keywords | Organoids, Engineered materials, Cell-matrix interactions, Biomaterials, Hydrogels |
| Literature Type | Journal Article |
| ISSN | 2058-8437 |
| Pages | 606-622 |
| Issue | 4(9) |
| Authors | Michael J Kratochvil, Alexis J Seymour, Thomas L Li, Sergiu P Paşca, Calvin J Kuo, Sarah C Heilshorn |
TL;DR
This review discusses the potential of engineered matrices to enhance organoid cultures, which better replicate human organ biology compared to traditional 2D systems. By optimizing the biochemical and biophysical properties of these matrices, researchers can improve reproducibility and control in organoid generation, thereby advancing the study of organ-level biology and its applications in regenerative medicine and disease modeling.
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Organoids · Engineered materials · Cell-matrix interactions · Biomaterials · Hydrogels
Abstract
Organoids are 3D cell culture systems that mimic some of the structural and functional characteristics of an organ. Organoid cultures provide the opportunity to study organ-level biology in models that mimic human physiology more closely than 2D cell culture systems or non-primate animal models. Many organoid cultures rely on decellularized extracellular matrices as scaffolds, which are often poorly chemically defined and allow only limited tunability and reproducibility. By contrast, the biochemical and biophysical properties of engineered matrices can be tuned and optimized to support the development and maturation of organoid cultures. In this Review, we highlight how key cell-matrix interactions guiding stem-cell decisions can inform the design of biomaterials for the reproducible generation and control of organoid cultures. We survey natural, synthetic and protein-engineered hydrogels for their applicability to different organoid systems and discuss biochemical and mechanical material properties relevant for organoid formation. Finally, dynamic and cell-responsive material systems are investigated for their future use in organoid research.
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Primary Questions Addressed
- How do the mechanical properties of engineered materials influence the differentiation of stem cells in organoid cultures?
- What specific biochemical signals can be incorporated into engineered hydrogels to enhance organoid maturation?
- In what ways do dynamic material systems improve the functionality and viability of organoid models compared to static scaffolds?
- How can the tunability of synthetic materials be leveraged to create organoid models that better replicate specific organ functions?
- What challenges are associated with the reproducibility of organoid cultures when using various engineered materials, and how can these be addressed?
Key Findings
Research Background and Purpose
Organoids are three-dimensional (3D) cell culture systems that replicate certain structural and functional characteristics of organs. They provide a more physiologically relevant model for studying organ-level biology compared to traditional two-dimensional (2D) cultures or animal models. This review discusses the limitations of current organoid culture methods, particularly the reliance on poorly defined decellularized extracellular matrices (ECMs), and emphasizes the potential of engineered biomaterials to enhance the reproducibility and functionality of organoid cultures.
Main Methods/Materials/Experimental Design
The review categorizes various biomaterials used for organoid culture into three main types: natural, synthetic, and protein-engineered hydrogels. It highlights the importance of cell-matrix interactions and presents a detailed discussion on the mechanical and biochemical properties of these materials.
- Natural Hydrogels: These include decellularized ECMs like Matrigel, which provide a complex environment but suffer from batch variability.
- Synthetic Hydrogels: These materials, such as polyethylene glycol (PEG), allow for precise tuning of properties and are more reproducible.
- Protein-Engineered Hydrogels: These offer a balance between the benefits of natural materials and the tunability of synthetic options.
Key Results and Findings
- Engineered materials can be optimized for specific organoid types, enhancing their structural and functional characteristics.
- Synthetic and protein-engineered hydrogels demonstrated improved control over cell behavior, leading to more consistent organoid development.
- The study emphasizes the significance of dynamic biomaterials that can change properties in response to cellular activity, potentially guiding organoid maturation.
Main Conclusions/Significance/Innovation
The review concludes that engineered biomaterials have the potential to revolutionize organoid research by providing well-defined, tunable environments that enhance reproducibility and physiological relevance. These advancements could facilitate the development of organoids as reliable platforms for drug testing and disease modeling.
Research Limitations and Future Directions
Despite the advancements, challenges remain in achieving the full maturity and functionality of organoids. Future research should focus on:
- Developing engineered materials that can mimic the dynamic nature of native ECMs.
- Exploring the integration of organoids with organ-on-a-chip technologies to study inter-organ interactions.
- Utilizing patient-derived organoids to improve personalized medicine approaches.
Summary Table of Material Types and Their Characteristics
| Material Type | Characteristics | Examples |
|---|---|---|
| Natural Hydrogels | Complex, biologically relevant, variable | Matrigel, Collagen |
| Synthetic Hydrogels | Chemically defined, tunable, reproducible | PEG, Alginate |
| Protein-Engineered | Well-defined, mimics natural ECM properties | Elastin-like proteins |
This structured approach to summarizing the review captures the essence of the research while highlighting the innovative aspects and future directions in the field of organoid systems.
References
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Literatures Citing This Work
- iPSCs-Based Neural 3D Systems: A Multidimensional Approach for Disease Modeling and Drug Discovery. - Gianluca Costamagna;Luca Andreoli;Stefania Corti;Irene Faravelli - Cells (2019)
- Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications. - Daniel Fan;Urs Staufer;Angelo Accardo - Bioengineering (Basel, Switzerland) (2019)
- Vertically-Aligned Functionalized Silicon Micropillars for 3D Culture of Human Pluripotent Stem Cell-Derived Cortical Progenitors. - Alessandro Cutarelli;Simone Ghio;Jacopo Zasso;Alessandra Speccher;Giorgina Scarduelli;Michela Roccuzzo;Michele Crivellari;Nicola Maria Pugno;Simona Casarosa;Maurizio Boscardin;Luciano Conti - Cells (2019)
- Bioengineered microenvironment to culture early embryos. - Zhen Gu;Jia Guo;Hongmei Wang;Yongqiang Wen;Qi Gu - Cell proliferation (2020)
- Gastrointestinal tract modeling using organoids engineered with cellular and microbiota niches. - Sungjin Min;Suran Kim;Seung-Woo Cho - Experimental & molecular medicine (2020)
- Effect of Laminin Derived Peptides IKVAV and LRE Tethered to Hyaluronic Acid on hiPSC Derived Neural Stem Cell Morphology, Attachment and Neurite Extension. - T Hiran Perera;Xi Lu;Laura A Smith Callahan - Journal of functional biomaterials (2020)
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- Topographic Cues Impact on Embryonic Stem Cell Zscan4-Metastate. - Carlo F Natale;Tiziana Angrisano;Luigi Pistelli;Geppino Falco;Viola Calabrò;Paolo A Netti;Maurizio Ventre - Frontiers in bioengineering and biotechnology (2020)
- Tools for probing host-bacteria interactions in the gut microenvironment: From molecular to cellular levels. - Kimberly A Wodzanowski;Samantha E Cassel;Catherine L Grimes;April M Kloxin - Bioorganic & medicinal chemistry letters (2020)
- Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids. - Victor Hernandez-Gordillo;Timothy Kassis;Arinola Lampejo;GiHun Choi;Mario E Gamboa;Juan S Gnecco;Alexander Brown;David T Breault;Rebecca Carrier;Linda G Griffith - Biomaterials (2020)
... (145 more literatures)
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