In the last three decades massive progress in the fabrication of advanced physiological twins capable of recapitulating specific functions of tissues and organs in vitro, have been made. The applications of tissue engineering have considerably broadened from the simple manufacturing of tissue substitutes, towards being an answer to today’s main biomedical challenges, including drug development, tissue/organ modelling, and precision medicine. Nevertheless, certain hurdles, notably the successful emulation of a functional vascular system and an immune system drainage network, remain unresolved. The present study aimed at exploring and create innovative tools accessible for precision medicine purposes, involving different pathophysiological conditions. The main body of this thesis is divided into three sections. The first part focused on the development of a bioactive biomaterial suitable for both in vivo re-vascularization of ischemic tissues and, in vitro, biofabrication of biomimetic vascularized tissues. This novel approach provides a new strategy to maximize the applications of endothelial cellderived extracellular vesicles (EVs) applications and their angiogenic cargo in tissue engineering. The results demonstrated that EVs-functionalized hydrogel promoted the formation of functional neovascular networks in vivo and improved cardiac performance and revascularization, in acute myocardial infarction (AMI). The second and third sections of the thesis focused on the design and testing of a Modulable Biological Environments (MBE) bioreactor recapitulating physiological microenvironment in vitro. The MBE facilitated the assembling of complex patient-specific pathophysiological scenarios to study the interplay between the immune system and the progression of diseases. The combination of the MBE with induced pluripotent stem cells (iPSC) and bioinspired biomaterials was applied to two different scenarios: mixed anxiety-depressive disorder (MADD) and triple-negative breast cancer (TNBC). The bioengineered vessel embedded in the MBE allows the draining of immune cells and fluids inside bioassembled organs, to test new therapeutic approaches. The three projects under discussion share a common objective: to develop sophisticated in vitro models that closely mimic the unique features of various pathological processes. To accurately replicate the specific characteristics of tissues and diseases, each project has employed different techniques of biofabrication and bioassembling. These include 3D bioprinting, which allows for precise layer-by-layer construction of tissue models, microfluidics for simulating the dynamic environment of biological systems, and the generation of advanced cellular models like organoids. This multifaceted approach ensures a more comprehensive and accurate emulation of the complex biological and pathological conditions being studied. The innovative obtained findings support the development of new advanced bioengineering applications for regenerative medicine and the modelling in vitro.

Advanced 3D pathophysiological models for precision medicine

MAIULLARI, FABIO
2023

Abstract

In the last three decades massive progress in the fabrication of advanced physiological twins capable of recapitulating specific functions of tissues and organs in vitro, have been made. The applications of tissue engineering have considerably broadened from the simple manufacturing of tissue substitutes, towards being an answer to today’s main biomedical challenges, including drug development, tissue/organ modelling, and precision medicine. Nevertheless, certain hurdles, notably the successful emulation of a functional vascular system and an immune system drainage network, remain unresolved. The present study aimed at exploring and create innovative tools accessible for precision medicine purposes, involving different pathophysiological conditions. The main body of this thesis is divided into three sections. The first part focused on the development of a bioactive biomaterial suitable for both in vivo re-vascularization of ischemic tissues and, in vitro, biofabrication of biomimetic vascularized tissues. This novel approach provides a new strategy to maximize the applications of endothelial cellderived extracellular vesicles (EVs) applications and their angiogenic cargo in tissue engineering. The results demonstrated that EVs-functionalized hydrogel promoted the formation of functional neovascular networks in vivo and improved cardiac performance and revascularization, in acute myocardial infarction (AMI). The second and third sections of the thesis focused on the design and testing of a Modulable Biological Environments (MBE) bioreactor recapitulating physiological microenvironment in vitro. The MBE facilitated the assembling of complex patient-specific pathophysiological scenarios to study the interplay between the immune system and the progression of diseases. The combination of the MBE with induced pluripotent stem cells (iPSC) and bioinspired biomaterials was applied to two different scenarios: mixed anxiety-depressive disorder (MADD) and triple-negative breast cancer (TNBC). The bioengineered vessel embedded in the MBE allows the draining of immune cells and fluids inside bioassembled organs, to test new therapeutic approaches. The three projects under discussion share a common objective: to develop sophisticated in vitro models that closely mimic the unique features of various pathological processes. To accurately replicate the specific characteristics of tissues and diseases, each project has employed different techniques of biofabrication and bioassembling. These include 3D bioprinting, which allows for precise layer-by-layer construction of tissue models, microfluidics for simulating the dynamic environment of biological systems, and the generation of advanced cellular models like organoids. This multifaceted approach ensures a more comprehensive and accurate emulation of the complex biological and pathological conditions being studied. The innovative obtained findings support the development of new advanced bioengineering applications for regenerative medicine and the modelling in vitro.
2023
Inglese
GARGIOLI, CESARE
Università degli Studi di Roma "Tor Vergata"
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/214470
Il codice NBN di questa tesi è URN:NBN:IT:UNIROMA2-214470