P-01

The toxicology testing in the REACH project (Registration, Evaluation, Authorization and restriction of Chemicals) is estimated to cost millions of animals. The solution to this lies in nanotechnology. The progresses in this field opens the door to the miniaturization of laboratories and the formation of rudimentary organs. The Organ-on-a-chip can be made with human cells and can be the missing link between animal testing and tests on healthy humans.

It is also recognised that cells cultured in a 2D monolayer show different properties than when in a 3D environment (1). 3D in vitro models already show more accurate predictions than a 2D monolayer (1,2). It is possible to apply stem cells to a 3D construct and allow the cells to create their own environment by inducing differentiation (3). Differentiation is most stable when the tissue supports itself and by mimicking the cell-cell interaction it is possible to steer differentiating cells in a certain direction (4,5). This is accomplished by creating a lipid bilayer on a solid surface. This supported lipid bilayer (SLB) is build up out of the same lipids as a cell membrane (5). The SLB can subsequently be loaded with peptides in order to functionalize the SLB to direct cells to adhere and differentiate in the desired direction (4,5).

Multipotent mesenchymal stem cells (MSCs) can differentiate into mature osteoblasts after receiving chemical cues from their environment, existing of ECM and adjacent cells (3,5). Culturing MSCs with an SLB functionalized with BMP-2, TGF-β and RGD ligands within a PDMS structure will induce the formation of a stable 3D bone construct that can be used in an Organ-on-a-chip setting suitable for toxicology testing.

(1) Nguyen, D. G.; Funk, J.; Robbins, J. B.; Crogan-Grundy, C.; Presnell, S. C.; Singer, T.; Roth, A. B. Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity in Vitro. PLoS One 2016, 11 (7), 1–17.

(2) Materne, E.-M.; Maschmeyer, I.; Lorenz, A. K.; Horland, R.; Schimek, K. M. S.; Busek, M.; Sonntag, F.; Lauster, R.; Marx, U. The Multi-Organ Chip - A Microfluidic Platform for Long-Term Multi-Tissue Coculture. J. Vis. Exp. 2015, No. 98, 1–11.

(3) Rutkovskiy, A.; Stensløkken, K.-O.; Vaage, I. J. Osteoblast Differentiation at a Glance. Med. Sci. Monit. Basic Res. 2016, 22, 95–106.

(4) Koçer, G.; Jonkheijm, P. Guiding hMSC Adhesion and Differentiation on Supported Lipid Bilayers. Adv. Healthc. Mater. 2017, 6 (3), 1600862.

(5) van Weerd, J.; Karperien, M.; Jonkheijm, P. Supported Lipid Bilayers for the Generation of Dynamic Cell-Material Interfaces. Adv. Healthc. Mater. 2015.