ArticleMaterials science & engineering. C, Materials for biological applications2021
Fabrication of PNIPAm-based thermoresponsive hydrogel microwell arrays for tumor spheroid formation.
Article in Materials science & engineering. C, Materials for biological applications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Unlocking the Potential of Spheroids in Personalized Medicine: A Systematic Review of Seeding Methodologies.International journal of molecular sciences · 2025Pooled it
- Sorafenib nanomedicine in HCC: nano-bio interactions and combination therapies.Journal of nanobiotechnology · 2026Review
- Generation of Individualized, Standardized, and Electrically Synchronized Human Midbrain Organoids.Cells · 2025Article
- Immune cell targeting-mediated cytomimetic drug delivery system for BBB-penetrating and precise therapy of in situ glioma.Materials today. Bio · 2025Article
- Multifunctional Hydrogels for Advanced Cancer Treatment: Diagnostic Imaging and Therapeutic Modalities.Gels (Basel, Switzerland) · 2025Review
- A Thermo-responsive collapse system for controlling heterogeneous cell localization, ratio and interaction for three-dimensional solid tumor modeling.bioRxiv : the preprint server for biology · 2024Article
- Fabrication of Microstructured Hydrogels via Dehydration for On-Demand Applications.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Imaging-Based Efficacy Evaluation of Cancer Immunotherapy in Engineered Tumor Platforms and Tumor Organoids.Advanced healthcare materials · 2024Review
- Utility of 1.5 Tesla MRI Scanner in the Management of Small Sample Sizes Driven from 3D Breast Cell Culture.International journal of molecular sciences · 2024Article
- Knockout cancer by nano-delivered immunotherapy using perfusion-aided scaffold-based tumor-on-a-chip.Nanotheranostics · 2024Review
- Wound Microenvironment Self-Adjusting Hydrogels with Thermo-Sensitivity for Promoting Diabetic Wound Healing.Gels (Basel, Switzerland) · 2023Article
- Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The interplay of cells, polymers, and vascularization in three-dimensional lung models and their applications in COVID-19 research and therapy.Stem cell research & therapy · 2023Review
- Smart Triboelectric Nanogenerators Based on Stimulus-Response Materials: From Intelligent Applications to Self-Powered Systems.Nanomaterials (Basel, Switzerland) · 2023Review
- The Use of Biomaterials in Three-Dimensional Culturing of Cancer Cells.Current issues in molecular biology · 2023Review
- Biodegradable and Inherently Fluorescent pH-Responsive Nanoparticles for Cancer Drug Delivery.Pharmaceutical research · 2022Article
- Validation and scalability of homemade polycaprolactone macrobeads grafted with thermo-responsive poly(N-isopropylacrylamide) for mesenchymal stem cell expansion and harvesting.Biotechnology and bioengineering · 2022Article
- Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures.International journal of molecular sciences · 2022Review
- Systems andFrontiers in pharmacology · 2022Article
- Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Complex three-dimensional (3D) cell cultures are being increasingly implemented in biomedical research as they provide important insights into complex cancer biology, and cell-cell and cell-matrix interactions in the tumor microenvironment. However, most methods used today for 3D cell culture are limited by high cost, the need for specialized skills, low throughput and the use of unnatural culture environments. We report the development of a unique biomimetic hydrogel microwell array platform for the generation and stress-free isolation of cancer spheroids. The poly N-isopropylacrylamide-based hydrogel microwell array (PHMA) has thermoresponsive properties allowing for the attachment and growth of cell aggregates/ spheroids at 37 °C, and their easy isolation at room temperature (RT). The reversible phase transition of the microwell arrays at 35 °C was confirmed visually and by differential scanning calorimetry. Swelling/ shrinking studies and EVOS imaging established that the microwell arrays are hydrophilic and swollen at temperatures <35 °C, while they shrink and are hydrophobic at temperatures >35 °C. Spheroid development within the PHMA was optimized for seeding density, incubation time and cell viability. Spheroids of A549, HeLa and MG-63 cancer cell lines, and human lung fibroblast (HLF) cell line generated within the PHMAs had relatively spherical morphology with hypoxic cores. Finally, using MG-63 cell spheroids as representative models, a proof-of-concept drug response study using doxorubicin hydrochloride was conducted. Overall, we demonstrate that the PHMAs are an innovative alternative to currently used 3D cell culture techniques, for the high-throughput generation of cell spheroids for disease modeling and drug screening applications.
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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.