ArticlePloS one2016
Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.
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Who cites it
157 citing papers in PubMed, 367 citations in OpenAlex.
- A Hybrid Bioprinting-Microfabrication Approach to Controllable Multitype Spheroid Arrays for Modeling Tumor Heterogeneity.Advanced healthcare materials · 2026Article
- New approach methodologies to model liver fibrosis in metabolic dysfunction-associated steatohepatitis.BMB reports · 2026Review
- A human liver organoid platform for hepatotoxicity assessment: evaluation using reference compounds.Frontiers in toxicology · 2026Article
- Integrating 3D bioprinting and neural stem cell therapy for central nervous system repair: implications for regenerative neurosurgery.Frontiers in bioengineering and biotechnology · 2026Review
- Microphysiological systems as an emerging in vitro approach for the evaluation of drug absorption, distribution, metabolism, and excretion and toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Generation and applications of an expandable and mature hiPSC-derived liver organoid.Acta pharmaceutica Sinica. B · 2025Article
- Engineering a GelMA-dECM-based 3D bioprinted liver fibrosis model: methotrexate-induced functional and molecular validation.RSC advances · 2025Article
- Head and Neck 3D Bioprinting-A Review on Recent Advancements in Soft Tissue 3D Bioprinting and Medical Applications.Journal of functional biomaterials · 2025Review
- Pharmacists' Perceptions of 3D Printing and Bioprinting as Part of Personalized Pharmacy: A Cross-Sectional Pilot Study in Bulgaria.Pharmacy (Basel, Switzerland) · 2025Article
- Cell therapy for liver disorders: past, present and future.Nature reviews. Gastroenterology & hepatology · 2025Review
- In vitro-in silico analysis reveals that loss of tankyrase1/2 improves bile acid handling in genetically engineered HepG2 cultures.Archives of toxicology · 2025Article
- Assessing the landscape of clinical and observational trials involving bioprinting: a scoping review.3D printing in medicine · 2025Article
- In Vivo and In Vitro Models of Hepatic Fibrosis for Pharmacodynamic Evaluation and Pathology Exploration.International journal of molecular sciences · 2025Review
- Bridging the gap: the role of 3D cell cultures in mimicking tumor microenvironment for enhanced drug testing accuracy.Frontiers in bioengineering and biotechnology · 2025Review
- Impact of Post-Thaw Enrichment of Primary Human Hepatocytes on Steatosis, Inflammation, and Fibrosis in the TruVivoPharmaceuticals (Basel, Switzerland) · 2024Article
- Surface Functionalization of 3D-Printed Bio-Inspired Scaffolds for Biomedical Applications: A Review.Biomimetics (Basel, Switzerland) · 2024Review
- Advances in drug-induced liver injury research: in vitro models, mechanisms, omics and gene modulation techniques.Cell & bioscience · 2024Review
- Progress in Organ Bioprinting for Regenerative Medicine.Engineering (Beijing, China) · 2024Article
- Article
- Liver organoids: updates on generation strategies and biomedical applications.Stem cell research & therapy · 2024Review
97 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI). This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM). Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.