DataVXAdvanced MaterialsPaper
journal article·2026-05Open access

Bottom‐Up Programming of Cell States in Cancer Organoids with Defined Synthetic Adhesion Cues

Ali Nadernezhad, Verena J. Kast, Dagmar Pette, Franziska Baenke, Daniel E. Stange, Carsten Werner, Daniela Loessner

Advanced Materials· Volume 38· Issue 27
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Source abstract

Abstract

ABSTRACT Despite advances in defined culture systems, current organoid models lack programmable control of transcriptomic states beyond fixed genetic constraints or broadly specific microenvironmental conditions. Here, a bottom‐up biomaterial‐based platform is introduced to program cell state changes in pancreatic cancer organoids by tuning minimal adhesion cues within a synthetic matrix. A Design of Experiments framework is used to systematically model the patient‐specific transcriptome‐wide impact of matrix‐presented adhesion cues. Focusing on epithelial‐mesenchymal transition (EMT) as a proof‐of‐concept cellular program, a multiobjective optimization approach is applied to identify patient‐specific matrix compositions that enrich EMT‐associated transcriptional programs. Organoids cultured in these optimized matrices exhibit transcriptomic signatures consistent with EMT enrichment and coordinated shift in EMT‐associated regulatory signatures. Secretome profiling further reveals changes in cytokines previously linked to EMT‐associated inflammatory, hypoxia, and TGF‐β signaling. Together, these findings demonstrate that quantitative and targeted modulation of defined adhesion cues enables programmable control of transcriptomic states in pancreatic cancer organoids.
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Research context

Biomaterials

OpenAlex topics: Cancer Cells and Metastasis · Mathematical Biology Tumor Growth · 3D Printing in Biomedical Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Division of Polymer Biomaterials Science Leibniz Institute of Polymer Research Dresden Dresden Germany

Department of Visceral Thoracic and Vascular Surgery University Hospital Carl Gustav Carus Medical Faculty Dresden University of Technology Dresden Germany

National Center for Tumor Diseases Dresden (NCT/UCC) a partnership between DKFZ Faculty of Medicine and University Hospital Carl Gustav Carus Dresden University of Technology and Helmholtz‐Zentrum Dresden‐Rossendorf (HZDR) Dresden Germany

German Cancer Consortium (DKTK), Partner Site Dresden German Cancer Research Center (DKFZ) Dresden Germany

Center for Regenerative Therapies Dresden Dresden University of Technology Dresden Germany

Department of Chemical and Biological Engineering and Department of Materials Science and Engineering Faculty of Engineering Monash University Melbourne Australia

Department of Anatomy and Developmental Biology Biomedicine Discovery Institute Faculty of Medicine Nursing and Health Sciences Monash University Melbourne Australia

Funding

European Research Council

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