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Updated: Jul 3, 2026
09:03
Modified In Vivo Matrix Gel Plug Assay for Angiogenesis Studies
Published on: June 30, 2023
Animal-free matrix alternative for three-dimensional in vitro angiogenesis models
Elle Koivunotko1, Chris S Pridgeon1, Lauri Paasonen2
1Division of Pharmaceutical Biosciences, Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Frontiers in Toxicology
|July 2, 2026
Summary
A novel plant-derived hydrogel offers a reproducible, animal-free model for studying angiogenesis. This 3D model using human cells shows potential for ethical drug screening and regenerative therapies.
Area of Science:
- Biomaterials Science
- Cell Biology
- Regenerative Medicine
Background:
- Angiogenesis, the formation of new blood vessels, is crucial for tissue survival and is implicated in diseases like cancer.
- Current in vitro angiogenesis models often rely on animal-derived materials, hindering ethical research and reproducibility.
- Developing animal-free, physiologically relevant in vitro models is essential for advancing the 3Rs (Replacement, Reduction, Refinement) in scientific research.
Purpose of the Study:
- To develop and characterize a novel, animal-free 3D angiogenesis model using plant-derived nanofibrillated cellulose hydrogel (NFCh).
- To evaluate the efficacy of NFCh as a matrix for culturing human endothelial and stromal cells to form vascular networks.
- To compare the performance of the NFCh model with conventional animal-derived matrices.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) and human adipose-derived stromal cells (hASCs) were cultured in NFCh hydrogels of varying concentrations (0.125%-2.4%).
- Optimization of NFCh concentration for capillary-like structure formation was determined by stimulating HUVECs.
- Co-culture of HUVECs and hASCs in optimized NFCh concentrations was followed by imaging and proteomics analysis.
Main Results:
- Formation of capillary-like structures comparable to animal-derived extracellular matrix (ECM) controls was observed.
- NFCh concentration influenced protein expression, with lower concentrations (0.125%) showing higher angiogenesis markers and higher concentrations (1.5%) showing increased ECM markers.
- Vascular network morphology and organization were tunable by adjusting NFCh concentration.
Conclusions:
- Nanofibrillated cellulose hydrogel (NFCh) presents a promising, reproducible, and animal-free alternative to traditional angiogenesis matrices.
- This novel model supports the development of ethical in vitro systems for regenerative therapies, toxicological testing, and drug screening.
- The NFCh-based model aligns with the principles of the 3Rs, offering a sustainable approach to angiogenesis research.
