Next-Generation Organ-on-a-Chip model for research and drug evaluation in fibrotic diseases

Progressive organ fibrosis is a debilitating medical problem that is often
caused by chronic inflammation, leading to excessive extracellular matrix (ECM)
depositions and ultimately organ failure. Fibrosis is a key hallmark of
systemic sclerosis (SSc) andmay affect multiple organs. To date, the mortality
of patients with SS is increased and the quality of life is decreased due to
the absence of an effective disease-modifying treatment against fibrosis. To
add, there is a huge heterogeneity between SSc patients and the disease
aetiology is still poorly understood. However, to get a better disease
understanding, to identify diagnostic and prognostic biomarkers, perform drug
screening and to design clinical trials and precision medicine, a reliable
disease model is required. The existing in vitro models lack essential disease
features while animal models are unable to completely model a fibrotic disease
due to the major interspecies differences. In this study, we will develop an
organ-on-a-chip model that incorporates crucial SSc features such as the
inclusion of human cell types, extracellular matrix, biomechanical cues and
hypoxia. This model will then be used to evaluate anti-fibrotic and anti-SSc
therapies.

The main objective of this study is to evaluate the effect of
anti-fibrotic/anti-SSc therapies using a SSc organ-on-a-chip (OoC) model. The
secondary objectives of the study are:
- To engineer an advanced OoC device to model SSc that incorporates key disease
features
- To identify specific disease signatures using patient-specific SSc OoC models
for patient stratification, to facilitate SSc diagnosis and prognosis and to
better understand the aetiology and progression of the disease

In vitro experimental study; collection of skin biopsies and blood of patients
with SSc and blood from healthy volunteers for developing and employing an in
vitro research model. The in vitro model will be used to evaluate therapies.

For the study, all volunteers will undergo a venapunction which implies only a
minor inconvenience for most, but volunteers can stop the blood donation at any
time. This is a basic procedure and the risks for all participants are
negligible.
All participants with SSc will have skin biopsies taken under local anesthesia,
this will be a mild inconvenience as after the procedure the place of the
biopsy can hurt for a while and can lead to the formation of a small scar. As
this is also a basic procedure the risks for participants are negligible. The
results of the study are expected to contribute to a better understanding of
the disease in a patient-specific manner, which will lead to more personalized
medicine, which in the future will benefit all SSc patients.