Novel Gelatin Biomaterial Could Improve 3D Models in Cancer Immunotherapy

3D biofabrication models reflect increasing global awareness of the ethics of preclinical studies and an increased need for determining therapeutic efficacy differences.

Rousselot (Darling Ingredients) announced that highly purified gelatin biomaterials may improve the reliability and reproductivity of 3D in vitro models, according to a recent press release. The company suggests that 3D models with biomaterials could one day replace preclinical animal trials and improve cancer care.1

“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 Kathleen Jacobs, Global Regulatory Affairs director, Rousselot, in the press release.1

3D biofabrication models reflect changes occurring within the European Union, FDA, and show the increasingly awareness of ethical, effective studies, according to the investigators.1 They are a type of 3D bioprinting that uses biomaterials to reproduce a pathophysiological environment. In turn, investigators can study the efficacy of novel therapeutics.2

These models have advanced the development of novel biomaterials, but these biomaterials often contain high levels of endotoxins. These endotoxins can contaminate the model by decreasing the ability to engineer cartilage tissues, inhibiting dermal wound healing processes, and may create a marked inflammatory response in in vitro immune cells, which could enable cancer cells to proliferate in vivo.2

Investigators at University of Twente in the Netherlands, and Rousselot Biomedical used a 3D model to study the impact of endotoxins on breast tumor-immune cancer.1 The team compared the 3D models using purified biomaterials with low endotoxin levels (standard gelatins and GelMAs or Rousselot’s X-PURE gelatin and X-PURE GelMA).1

They observed that high endotoxin levels could significantly impact the efficacy of the 3D-printed model. First, endotoxins reflected the presence of inflammatory reaction. In the contaminated models, high endotoxin levels were shown to catalyze a strong inflammatory response in immune cells (macrophages).1

In addition, the 3D model showed that high endotoxin levels were associated with a reduction in crosstalk between immune cells and cancer cells. Finally, the artificial environment with high endotoxin levels impacted the reliability of the therapeutic outcomes.1

The biomaterials used for the models can “reduce the costs, time and ethical concerns associated with drug development,” said Bjorn Vergauwen, scientific director, Product and Process Development, Rousselot, in the press release.1

X-Pure GelMA is the first gelatin methacryloyl produced under GMP conditions. it is ultra-pure, which makes it practical for use in 3D bioprinting, regenerative medicine, and tissue engineering, according to the company.1

“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,” Jacobs said in the press release.1

References

  1. Rousselot. New study shows low endotoxin biomaterials improve reliability of 3D in vitro models; Pave the way for reduced animal testing. News Release. March 15, 2023. Accessed on March 15, 2023. https://www.sciadnewswire.com/news/772/new-study-shows-low-endotoxin-biomaterials-improve-reliability-3d-vitro-models-pave-way
  2. Heinrich M, Heinrich L, Ankone M, Vergauwen B, Prakesh J. Endotoxin contamination alters macrophage-cancer cell interaction and therapeutic efficacy in pre-clinical 3D in vitro models. Biomaterials Advances. January 2023. Accessed March 16, 2023. https://www.sciencedirect.com/science/article/pii/S2772950822004976?via%3Dihub
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