ETD system

Electronic theses and dissertations repository


Tesi etd-04152019-173128

Thesis type
Tesi di dottorato di ricerca
Advanced In-vitro Models with Integrated Sensing for Real-time Monitoring of Electrical and Mechanical Properties of Cellular Constructs
Settore scientifico disciplinare
Corso di studi
tutor Prof.ssa Ahluwalia, Arti Devi
tutor Dott. Mattei, Giorgio
tutor Prof. Domenici, Claudio
Parole chiave
  • bioreactors
  • in-vitro models
  • biological barrier monitoring
  • cellular impedance
  • viscoelasticity
  • mechanical properties monitoring
  • engineering hydrogel viscoelasticity
Data inizio appello
Data di rilascio
Riassunto analitico
The aim of this work of thesis was to contribute to the engineering of physiologically
relevant in-vitro models with the design of systems able to mimic and monitor the dynamic
environment of cellular constructs. These advanced models are emerging as a powerful
solution to bridge the gap between basic and clinical research, currently hindered by the
low predictivity and limited successful translation rate of animal models.
In particular, a cellular impedance-meter was designed and interfaced with a dual-flow
bioreactor to monitor the electrical properties of biological barriers. Indeed, epithelial and
endothelial tissue allow the separation of different compartments in the human body and
are normally exposed to shear stress on both sides (e.g. blood and interstitial fluid flow).
The system was validated with an intestinal model, demonstrating that dynamic conditions
contribute significantly to the tightness of the barrier. Possible applications of the system
range from drug testing to the study of several pathologic conditions related with an
alteration of barrier functions.
Since it is well known that mechanical properties of tissues dynamically evolve during
growth, ageing or diseases like fibrosis, different methods were investigated to modulate
spatial and temporal viscoelastic properties of hydrogel-based scaffolds. In order to
monitor mechanical properties of cellular constructs in real-time, the MechanoCulture
TR (MCTR) bioreactor was re-engineered in collaboration with the Canadian company
CellScale. Finally, a model of liver fibrosis was implemented mimicking in-vitro the
‘healthy’-fibrotic transition with an enzymatic stiffening method and monitoring the
mechanical properties of hepatocyte laden gels in the MCTR. The results obtained represent
a first step towards physiologically relevant models useful in the understanding of fibrosis
mechanobiological mechanisms and progression or in the study of antifibrotic drugs.
In conclusion, during the PhD, advanced models with integrated sensing for the real-time
monitoring of electrical and mechanical properties of cell construct were designed, tested
and validated. The results obtained have relevant implications both in the medical field,
contributing to the study of disease development, and in the pharmaceutic and cosmetic
fields, providing reliable tools for testing chemical compounds and drugs.