In oncology, 97% of drug candidates fail in clinical trials. This highlights a lack of relevance of preclinical models used upstream. Indeed, human in vitro models don’t consider the Tumoral Extracellular Matrix (TECM). However, more and more studies demonstrate that ECM composition and stiffness are modified in tumors and are linked to cancer initiation, progression, propagation, and drug resistances. BIOMIMESYS® is a Hyaluronic Acid-based matrix grafted with structural and adhesion molecules, which mimics the ECM/TECM. It is chemically defined and its composition and stiffness can be modified to reproduce the organ-specificity of the ECM, or to mimic a pathological microenvironment in vitro. We have demonstrated that the exposition of colon cancer cells cultured in BIOMIMESYS® Oncology matrix to an anti-proliferative drug showed a closer in vitro/in vivo correlation in the EC50 curve compared to 2D culture. Cancer cells can be advantageously grown in BIOMIMESYS® for several weeks in multiwell plates and in microfluidic chips for more advanced models. We also observed that modifications in the matrix composition and stiffness modify the cell behavior. Moreover, thanks to collaborations with academic laboratories, we demonstrated that BIOMIMESYS® allows to reproduce in vitro the behavior of cancerous cells in vivo, like mutation effects and metastasis propagation, and could be a relevant alternative to animal models. These results showed that the matricial microenvironment modifies the cell behavior in vitro and should be considered carefully in drug discovery. BIOMIMESYS® hydroscaffold™ is adapted to High Content Screening and represented a powerful tool to better select drug candidate.

1. Véronique De Conto1*, Vaihere Cheung1, Méryl Roudaut1, Grégory Maubon1, Elodie Vandenhaute1, Zied Souguir1, Nathalie Maubon1
1 HCS pharma, 250 rue Salvador Allende, Biocentre Fleming Bâtiment A, 59120 Loos, FRANCE
*veronique.deconto@hcs-pharma.com
Including the matricial tumoral microenvironment in 3D in vitro
models by using a Hyaluronic-Acid-based hydroscaffold™
The ECM has diverse
and crucial roles,
in health and disease
*GAG: Glycosaminoglycan
What is the Extracellular Matrix (ECM)?
Barnes et al., 2017
Adapted from Lu et al. 2021
Introduction
10 drug candidates 1 Drug
> 100K molecules
Preclinical trials: in vitro and in vivo
Pharmacology, toxicology, pharmacokinetics
Screening
Clinical trials:
phase I, II, III (and IV)
• Low success rate in drug discovery:
90% of failure in clinical trials (safety and efficacy)
Lack of relevance of preclinical models
• Animals: inter-species differences
• In vitro models: too simple, don’t take into account the
microenvironment, including the Extracellular Matrix (ECM)
Materials and methods
BIOMIMESYS® offers a better
correlation with in vivo data
regarding anticancer drug
efficacy.
Colon cancer cell line
Colon cancer cells invade the
matrix as growing spheroids.
BIOMIMESYS® allows long term culture, and
chronic (repeated doses) treatments.
Colon cancer cell line
+ primary human macrophages Colon cancer cell line along time in BIOMIMESYS Oncology
Results
Conclusions: BIOMIMESYS® hydroscaffold™ reproduces the ECM. It is composed of purified, well-controlled components allowing batch-to-batch
consistency. It is suitable for various cell culture vessels and is compatible with High Content Screening platforms. It reproduces the stiffness and the
composition of healthy or pathological tissues, including cancer, and allows chronic treatments for a better in vivo/in vitro correlation
BIOMIMESYS® fills the gap between 3D cell culture systems and in vivo for a higher predictability of your cancer models, by reproducing the ECM.
Goal : To improve the predictivity of in vitro models by taking into
account the 3D cell organization and the microenvironment
What is BIOMIMESYS® hydroscaffoldTM?
Reference : Barnes, J.M., Przybyla, L., and Weaver, V.M. (2017). Tissue mechanics regulate brain development, homeostasis and disease. J Cell Sci 130, 71–82 ; Morgan, P., Brown, D.G., Lennard, S., Anderton, M.J., Barrett, J.C., Eriksson, U., Fidock, M., Hamrén, B., Johnson, A.,
March, R.E., et al. (2018). Impact of a five-dimensional framework on R&D productivity at AstraZeneca. Nat Rev Drug Discov 17, 167–181 ; Lu, P., Weaver, V.M., and Werb, Z. (2012). The extracellular matrix: A dynamic niche in cancer progression. The Journal of Cell Biology 196,
395. Wang, L., Johnson, J.A., Zhang, Q., and Beahm, E.K. (2013). Combining decellularized human adipose tissue extracellular matrix and adipose-derived stem cells for adipose tissue engineering. Acta Biomater 9, 8921–8931.
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