ArticleBiomaterials2018
Biomimetic and enzyme-responsive dynamic hydrogels for studying cell-matrix interactions in pancreatic ductal adenocarcinoma.
Article in Biomaterials, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 130 citations in OpenAlex.
- Tumor-Immune-On-Chip to Evaluate Pathophysiological Feature of T Lymphocytes Expanded from Patient Tumors and Lymph Node Tissues.Cancer medicine · 2026Trial
- Smart Bioinks for 4D Bioprinting: Requirements, Design, and Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Dynamic granular hydrogels to assess pancreatic cancer cell fate.Biomaterials science · 2026Article
- Smart microdevices for biomedical drug delivery: endogenous stimuli as the key to safer therapeutics.RSC advances · 2026Review
- Dynamic Gelatin Hydrogels Crosslinked by Dithiolane-Norbornene Click Chemistry.Macromolecular bioscience · 2026Article
- Targeted drug delivery systems for pancreatic cancer therapy: advances, challenges, and future perspectives.Frontiers in immunology · 2026Review
- Bio-Polymers Based Functionalized Hydrogel Carriers for Targeted Oncology Therapies: Current Progress and Future Perspectives.International journal of nanomedicine · 2026Review
- Dynamic hydrogel mechanics in organoid engineering: From matrix design to translational paradigms.Bioactive materials · 2026Review
- Enzymatic Methods for Assembling and Modifying Hydrogel Biomaterials.Regenerative engineering and translational medicine · 2025Article
- Bioengineering 3D Pancreatic Cancer Models with Fibrotic Stroma for In Vitro Cancer Modeling.Micromachines · 2025Review
- Engineering multifunctional surface topography to regulate multiple biological responses.Biomaterials · 2025Review
- Sustained intraocular pressure-lowering effect and biocompatibility of a single subconjunctival administration of hydrogel-encapsulated nano-brinzolamide.Journal of materials science. Materials in medicine · 2025Article
- Matrix Stiffness and Biochemistry Govern Colorectal Cancer Cell Growth and Signaling in User-Programmable Synthetic Hydrogels.ACS biomaterials science & engineering · 2025Article
- Mapping Tumor-Stroma-ECM Interactions in Spatially Advanced 3D Models of Pancreatic Cancer.ACS applied materials & interfaces · 2025Article
- Organoids technology in cancer research: from basic applications to advancedFrontiers in cell and developmental biology · 2025Review
- Hydrogel models of pancreatic adenocarcinoma to study cell mechanosensing.Biophysical reviews · 2024Review
- Recent advances in shape memory scaffolds and regenerative outcomes.Biomedical engineering letters · 2024Review
- Targeting the pancreatic tumor microenvironment by plant-derived products and their nanoformulations.Medical oncology (Northwood, London, England) · 2024Review
- Biomimetic Hydrogel Strategies for Cancer Therapy.Gels (Basel, Switzerland) · 2024Review
- Combined effects of matrix stiffness and obesity-associated signaling directs progressive phenotype in PANC-1 pancreatic cancer cellsbioRxiv : the preprint server for biology · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The tumor microenvironment (TME) governs all aspects of cancer progression and in vitro 3D cell culture platforms are increasingly developed to emulate the interactions between components of the stromal tissues and cancer cells. However, conventional cell culture platforms are inadequate in recapitulating the TME, which has complex compositions and dynamically changing matrix mechanics. In this study, we developed a dynamic gelatin-hyaluronic acid hybrid hydrogel system through integrating modular thiol-norbornene photopolymerization and enzyme-triggered on-demand matrix stiffening. In particular, gelatin was dually modified with norbornene and 4-hydroxyphenylacetic acid to render this bioactive protein photo-crosslinkable (through thiol-norbornene gelation) and responsive to tyrosinase-triggered on-demand stiffening (through HPA dimerization). In addition to the modified gelatin that provides basic cell adhesive motifs and protease cleavable sequences, hyaluronic acid (HA), an essential tumor matrix, was modularly and covalently incorporated into the cell-laden gel network. We systematically characterized macromer modification, gel crosslinking, as well as enzyme-triggered stiffening and degradation. We also evaluated the influence of matrix composition and dynamic stiffening on pancreatic ductal adenocarcinoma (PDAC) cell fate in 3D. We found that either HA-containing matrix or a dynamically stiffened microenvironment inhibited PDAC cell growth. Interestingly, these two factors synergistically induced cell phenotypic changes that resembled cell migration and/or invasion in 3D. Additional mRNA expression array analyses revealed changes unique to the presence of HA, to a stiffened microenvironment, or to the combination of both. Finally, we presented immunostaining and mRNA expression data to demonstrate that these irregular PDAC cell phenotypes were a result of matrix-induced epithelial-mesenchymal transition (EMT).
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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.