ArticleBiomaterials2012
Recreating the tumor microenvironment in a bilayer, hyaluronic acid hydrogel construct for the growth of prostate cancer spheroids.
Article in Biomaterials, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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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
58 citing papers in PubMed.
- Advances in 3D culture systems for maintaining prostate tissue architecture and functional ex vivo prostate organ culture for biomedical applications.Molecular biology reports · 2026Review
- TGFβ1 and RGD Cooperatively Regulate SMAD2/3-Mediated Oncogenic Effects in Prostate Cancer Cells in Bio-Orthogonally Constructed Hydrogels.ACS biomaterials science & engineering · 2025Article
- Article
- 3D tumor spheroids: morphological alterations a yardstick to anti-cancer drug response.In vitro models · 2023Review
- Alternative Non-Mammalian Animal and Cellular Methods for the Study of Host-Fungal Interactions.Journal of fungi (Basel, Switzerland) · 2023Review
- 3D-Printed Tumor-on-Chip for the Culture of Colorectal Cancer Microspheres: Mass Transport Characterization and Anti-Cancer Drug Assays.Bioengineering (Basel, Switzerland) · 2023Article
- HYDRHA: Hydrogels of hyaluronic acid. New biomedical approaches in cancer, neurodegenerative diseases, and tissue engineering.Materials today. Bio · 2022Review
- Three-dimensional in vitro culture models in oncology research.Cell & bioscience · 2022Review
- Multiple Cell Cultures for MRI Analysis.International journal of molecular sciences · 2022Review
- Article
- 3D Printed Solutions for Spheroid Engineering and Cancer Research.International journal of molecular sciences · 2022Article
- Evaluation of the Anti-Pharmaceutics · 2022Article
- Polymeric Hydrogels for In Vitro 3D Ovarian Cancer Modeling.International journal of molecular sciences · 2022Review
- 3D Cell Cultures: Evolution of an Ancient Tool for New Applications.Frontiers in physiology · 2022Review
- Biomimetic stiffening of cell-laden hydrogels via sequential thiol-ene and hydrazone click reactions.Acta biomaterialia · 2021Article
- Alginate Microencapsulation for Three-Dimensional In Vitro Cell Culture.ACS biomaterials science & engineering · 2021Review
- 3D Modeling of Epithelial Tumors-The Synergy between Materials Engineering, 3D Bioprinting, High-Content Imaging, and Nanotechnology.International journal of molecular sciences · 2021Review
- Advances in removing mass transport limitations for more physiologically relevantBiophysics reviews · 2021Review
- In vitro engineering of a bone metastases model allows for study of the effects of antiandrogen therapies in advanced prostate cancer.Science advances · 2021Article
- Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Cancer cells cultured in physiologically relevant, three-dimensional (3D) matrices can recapture many essential features of native tumor tissues. In this study, a hyaluronic acid (HA)-based bilayer hydrogel system that not only supports the tumoroid formation from LNCaP prostate cancer (PCa) cells, but also simulates their reciprocal interactions with the tumor-associated stroma was developed and characterized. HA hydrogels were prepared by mixing solutions of HA precursors functionalized with acrylate groups (HA-AC) and reactive thiols (HA-SH) under physiological conditions. The resultant viscoelastic gels have an average elastic modulus of 234 ± 30 Pa and can be degraded readily by hyaluronidase. The orthogonal and cytocompatible nature of the crosslinking chemistry permits facile incorporation of cytokine-releasing particles and PCa cells. In our bilayer hydrogel construct, the top layer contains heparin (HP)-decorated, HA-based hydrogel particles (HGPs) capable of releasing heparin-binding epidermal growth factor-like growth factor (HB-EGF) in a sustained manner at a rate of 2.5 wt%/day cumulatively. LNCaP cells embedded in the bottom layer receive the growth factor signals from the top, and in response form enlarging tumoroids with an average diameter of 85 μm by day 7. Cells in 3D hydrogels assemble into spherical tumoroids, form close cellular contacts through E-cadherin, and show cortical organization of F-actin, whereas those plated as 2D monolayers adopt a spread-out morphology. Compared to cells cultured on 2D, the engineered tumoroids significantly increased the expression of two pro-angiogenic factors, vascular endothelial growth factor-165 (VEGF(165)) and interleukin-8 (IL-8), both at mRNA and protein levels. Overall, the HA model system provides a useful platform for the study of tumor cell responses to growth factors and for screening of anticancer drugs targeting these pathways.
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