Abstract
Tissue engineering (TE) is a field of research developing biological substitutes that restore, maintain, and emulate tissue functions. Its applications span regenerative medicine, pharmaceutical testing, and biological research. TE holds the promise of reducing reliance on animal testing, enabling personalized medicine, and addressing the shortage of donor tissues. Traditional monitoring methods in TE, such as histological analysis, are typically offline, destructive, and time-consuming. These methods require parallelizing the TE process to allow for periodic sampling, which increases costs and reduces efficiency. Moreover, they provide only inferred information about the whole population, lacking the ability to pinpoint and track dynamic biological processes in real time. Therefore, to fully realize the potential of TE, efficient, non-destructive, and scalable monitoring methods are required. Electrical Impedance Tomography (EIT) emerges as a promising tool in this context. EIT enables non-invasive, real-time monitoring of 3D cell cultures, which are central to TE. By providing continuous insights into tissue maturation, EIT can significantly enhance the efficiency and affordability of TE processes. Current EIT systems are originally designed for large-scale applications like lung imaging or geophysical exploration and suffer from a low signal-to-noise ratio and limited space resolution. Moreover, they usually exploit model-based reconstruction algorithms that linearize and simplify the inherently ill-posed inverse problem of EIT, leading to modeling errors and reduced image accuracy. Therefore, to fully benefit from EIT approach, the system must be adapted to meet the specific demands of TE. This project aims to realize the “next-generation EIT system for non-destructive monitoring of tissue-engineered construct” by addressing all the scientific and technological challenges for the application of EIT approach at the cellular level, such as improved sensitivity, enhanced image reconstruction accuracy, biocompatibility at the cellular level, and correlation analysis between conductivity measurements and tissue maturation. A multidisciplinary and multimethodological approach will be used to tackle the complexity of EIT systems by combining engineering, data science, non-linear mathematics, and biology. The specific case of mineralization of bone tissue constructs will be used as case study, targeting the detection and localization of calcium crystals created during the maturation process. Specifically, this project aims to investigate the limit of detection of EIT systems in terms of the minimal spatial resolution and minimal conductivity gradient resolution by linking global system requirements to specifications on the hardware level. Based on that study, low-noise electronic design will be exploited for the development of the EIT hardware platform. The project will also explore the benefits of using additive manufacturing electronic technology for the realization of the 3D-printed miniaturized tank in order to have a unique container with well-defined positions of the electrodes, as they are printed together with the non-conductive resin. Multi-modal and multi-frequency approaches will be analyzed to improve the final accuracy of the reconstructed image by enhancing the a-priori information about the space localization of the construct and the specific characteristics of the materials. The combination of EIT with multi-spectral optical imaging can improve the accuracy of the reconstructed image by following a sensing-fusion approach, while multi-frequency EIT measurement can exploit the different spectral responses of different materials to better localize the mineralized material. Finally, non-linear data-driven reconstruction algorithms based on variational methods will also be studied for improving the quality of the reconstructed images. The final ambitious goal of th
Dettagli del progetto
Responsabile scientifico: Marco Crescentini
Strutture Unibo coinvolte:
Dipartimento di Ingegneria dell'Energia Elettrica e dell'Informazione "Guglielmo Marconi"
Coordinatore:
ALMA MATER STUDIORUM - Università di Bologna(Italy)
Contributo totale di progetto: Euro (EUR) 245.566,00
Contributo totale Unibo: Euro (EUR) 172.203,00
Durata del progetto in mesi: 24
Data di inizio
30/11/2023
Data di fine:
28/02/2026
