ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Engineered Hydrogels for Organoid Models of Human Nonalcoholic Fatty Liver Disease.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Immune-stromal interactions at the crossroads of tissue injury, repair, and tumor progression.Med (New York, N.Y.) · 2026Review
- Lipid network crosslinked hydrogels control material dynamics across multiple length scales through lipid movement.Nature communications · 2026Article
- Matrix stress relaxation drives glioblastoma cell response in viscoelastic biomaterials.Science advances · 2026Article
- Peroxisome proliferator-activated receptor gamma (PPARγ) as a mechano-metabolic transducer: coordinating lipid homeostasis through mechanical cues.Molecular biomedicine · 2026Review
- Extracellular matrix stiffness directs region-specific lung epithelial differentiation revealed by hPSC-derived lung organoids.Nature communications · 2026Article
- Label-free 4D holotomography with depth-adaptive segmentation for quantitative analysis of lipid droplet dynamics in hepatic organoids.Biophotonics discovery · 2026Article
- Microscale Mechanical Cues in Hydrogels: Engineering Strategies to Modulate Cell Fates in Three Dimensions.Cell biomaterials · 2026Article
- The Emerging Role of Mechanobiology in Connecting Metabolic and Cardiovascular Diseases: From Fundamentals to Future Therapies.Biomedicines · 2026Review
- Integrating mechanical cues inFrontiers in immunology · 2026Review
- Organoids in Cancer Research and Regenerative Medicine: Current Status, Challenges, and Future Prospects.MedComm · 2026Review
- Article
- Tuning viscoelasticity of dynamic covalent hydrogels for human tissue modeling.bioRxiv : the preprint server for biology · 2025Article
- Engineered Hydrogels for Organoid Models of Human Nonalcoholic Fatty Liver Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by increased lipid accumulation and excessive deposition of extracellular matrix (ECM) that results in tissue stiffening. The potential interplay between matrix stiffness and hepatocyte lipid accumulation during NAFLD has not been established. Here, an in vitro NAFLD model is developed using chemically defined, engineered hydrogels and human induced pluripotent stem cell-derived hepatic organoids (HOs). Specifically, dynamic covalent chemistry crosslinking, along with transient small molecule competitors, are used to create dynamic stiffening hydrogels that enable the reproducible culture of HOs. Within matrices that mimic the stiffness of healthy to diseased tissue (≈1-6 kPa), lipid droplet accumulation in HOs is triggered by exposure to an NAFLD-associated free fatty acid. These NAFLD model suggests that higher stiffness microenvironments result in increased hepatic lipid droplet accumulation, increased expression of fibrosis markers, and increased metabolic dysregulation. By targeting the ROCK mechanosignaling pathway, the synergy between matrix stiffness and lipid droplet accumulation is disrupted. The in vitro model of NAFLD has the potential to understand the role of mechanosignaling in disease progression and identify new pathways for therapeutic intervention.
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