New study shows low endotoxin biomaterials improve reliability of 3D in vitro models; Pave the way for reduced animal testing

Irving, United States, 15th March 2023 / Sciad Newswire / Darling Ingredients’ health brand Rousselot, the global leader¹ in collagen-based solutions, announced today that a new study has found that utilization of highly purified gelatin biomaterials for 3D in vitro models can significantly enhance the reliability and reproducibility in these models, creating new possibilities for replacing preclinical animal trials. 

“This study revealed that 3D models of novel breast cancer immunotherapies display clear therapeutic efficacy differences depending on the level of endotoxins in gelatins and methacryloyl gelatins (GelMA) used in in vitro systems,” said Dr. Kathleen Jacobs, Global Regulatory Affairs Director, Rousselot. “Biomaterials with low endotoxin content could lead to a more accurate representation of the safety and potency of novel therapeutics. This can improve the validity of 3D in vitro models and help to reduce animal testing.”  

The joint study² done by the University of Twente, The Netherlands, and Rousselot Biomedical investigated for the first time the impact of endotoxins on 3D breast tumor-immune cancer models. The research compared 3D models using standard gelatins and GelMAs or Rousselot’s X-PURE® gelatin and X-PURE® GelMA – purified biomaterials with low endotoxin levels (<10 EU/g).  

The study demonstrated that endotoxin levels had a marked effect on the validity of the 3D-printed model in three aspects: 

• Inflammatory reaction: The presence of high levels of endotoxins caused a strong inflammatory response in immune cells (macrophages) in contaminated models. 
• Receptivity of immune cells to cancer cells: Crosstalk between macrophages and cancer cells was significantly reduced in the presence of high endotoxin levels.  
• Reliability of therapeutic outcomes: The high endotoxin environment artificially increased the measured efficacy of the therapy designed to inhibit the expression of anti-inflammatory markers.  

Image 1: Illustration to show how the presence of endotoxins impacts the credibility of 3D models. This figure is a modified version of the original graphic in Heinrich, M. A., Heinrich, L., Ankone, M. J. K., Vergauwen, B., & Prakash, J. (2023). Endotoxin contamination alters macrophage-cancer cell interaction and therapeutic efficacy in pre-clinical 3D in vitro models. Biomaterials advances, 144, 213220. https://doi.org/10.1016/j.bioadv.2022.213220 Available under Creative Commons Attribution License (CC BY).

Recent changes in European Union³ and US Food and Drug Administration (FDA)⁴ legislation, combined with increased ethical considerations and efficacy demands, are driving the rapid replacement of pre-clinical animal trials with 3D biofabrication models. 

Dr Bjorn Vergauwen, Scientific Director, Product and Process Development, Rousselot concluded, “The use of purified biomaterials such as Rousselot’s X-Pure or X-Pure GelMA in in vitro 3D models is critical in producing a biologically relevant environment, while also helping to reduce the costs, time and ethical concerns associated with drug development.” 

Visit this link to access the study. 

1. Collagen, Market estimates and trend analysis, 2022 Grand View Research 
2. Marcel Alexander Heinrich, Lena Heinrich, Marc J.K. Ankone, Bjorn Vergauwen, Jai Prakash, Endotoxin contamination alters macrophage-cancer cell interaction and therapeutic efficacy in pre-clinical 3D in vitro models, Biomaterials Advances. 2023 (144). https://doi.org/10.1016/j.bioadv.2022.213220   
3. https://eur-lex.europa.eu/LexUriServ/LexUriServ.do
4. https://www.congress.gov/bill/117th-congress/senate-bill/5002  

ENDS

Notes to Editors

About Darling Ingredients 

Darling Ingredients Inc. (NYSE: DAR) is the largest publicly traded company turning edible by-products and food waste into sustainable products and a leading producer of renewable energy. Recognized as a sustainability leader, the company operates more than 250 plants in 17 countries and repurposes approximately 15% of the world's meat industry waste streams into value-added products, such as green energy, renewable diesel, collagen, fertilizer, animal proteins and meals and pet food ingredients. To learn more, visit darlingii.com and follow us on LinkedIn. 

About Rousselot Biomedical 

As the most recent strategic segment within Rousselot, Darling Ingredients’ Health Brand, we have drawn upon Rousselot’s 130+ years of worldwide expertise and proven track record of pharmaceutical gelatins and collagens to develop innovative ranges of purified, modified, and non-modified gelatins and collagens for biomedical applications. Offering unique advantages to assure performance, quality, and safety from bench to clinic, Rousselot X-PURE® and Rousselot QUALI-PURE® are backed by strong scientific data and ongoing research. Rousselot Biomedical is committed to supporting end-to-end partnerships to help “Improving patients’ lives”. www.rousselot.com/biomedical 

About X-Pure® GelMA 

X-Pure GelMA is the world’s first gelatin methacryloyl produced under GMP conditions, making it suitable for clinical applications in advanced biomedical applications. This premium biomaterial is ideal for 3D bioprinting, regenerative medicine and tissue engineering owing to its guaranteed ultra-low impurity levels, batch to batch consistency and tunable mechanical properties. As a result, X-Pure GelMA can reduce the development time between bench and bedside, for pharmaceuticals, medical devices, and Advanced Therapy Medicinal Products (ATMP). www.gelma.com 

For further information, please contact:

Rousselot

Caroline Brochard-Garnier

Director of Communications & PR, Rousselot

E: caroline.brochard-garnier@rousselot.com

Sciad Communications

Maria Patey / Sophie Protheroe

E: rousselot@sciad.com 

T: +44 (0)20 3405 7892