TY - JOUR
T1 - In vivoorganized neovascularization induced by 3D bioprinted endothelial-derived extracellular vesicles
AU - Maiullari, Fabio
AU - Chirivì, Maila
AU - Costantini, Marco
AU - Ferretti, Anna Maria
AU - Recchia, Sandro
AU - Maiullari, Silvia
AU - Milan, Marika
AU - Presutti, Dario
AU - Pace, Valentina
AU - Raspa, Marcello
AU - Scavizzi, Ferdinando
AU - Massetti, Massimo
AU - Petrella, Lella
AU - Fanelli, Mara
AU - Rizzi, Marta
AU - Fortunato, Orazio
AU - Moretti, Fabiola
AU - Caradonna, Eugenio
AU - Bearzi, Claudia
AU - Rizzi, Roberto
PY - 2021
Y1 - 2021
N2 - Extracellular vesicles (EVs) have become a key tool in the biotechnological landscape due to their well-documented ability of mediating intercellular communication. Such feature has been explored and, actually, it is under constant investigation by researchers, who have unraveled the important role of EVs in several research fields ranging from oncology, immunology and diagnostics to regenerative medicine. Unfortunately, there are still some limits to overcome before a clinical application, including the inability to confine the EVs to strategically defined sites of interest, to avoid side effects. In this study, for the first time, EVs application is supported by 3D bioprinting technology to develop a new strategy for applying the angiogenic cargo of HUVEC-derived EVs in regenerative medicine. EVs, derived from human endothelial cells and grown under different stressed conditions, were collected and used as bio-additives for the formulation of advanced bioinks. After in vivo sub-cutaneous implantation, we demonstrated that the bioprinted 3D structures, loaded with EVs, supported the formation of a new functional vasculature in situ, consisting of blood-perfused microvessels recapitulating the printed pattern. The results obtained in this study favor the development of new therapeutic approaches for critical clinical conditions, such as the need for prompt revascularization of ischemic tissues, which represents the fundamental substrate for advanced regenerative medicine applications.
AB - Extracellular vesicles (EVs) have become a key tool in the biotechnological landscape due to their well-documented ability of mediating intercellular communication. Such feature has been explored and, actually, it is under constant investigation by researchers, who have unraveled the important role of EVs in several research fields ranging from oncology, immunology and diagnostics to regenerative medicine. Unfortunately, there are still some limits to overcome before a clinical application, including the inability to confine the EVs to strategically defined sites of interest, to avoid side effects. In this study, for the first time, EVs application is supported by 3D bioprinting technology to develop a new strategy for applying the angiogenic cargo of HUVEC-derived EVs in regenerative medicine. EVs, derived from human endothelial cells and grown under different stressed conditions, were collected and used as bio-additives for the formulation of advanced bioinks. After in vivo sub-cutaneous implantation, we demonstrated that the bioprinted 3D structures, loaded with EVs, supported the formation of a new functional vasculature in situ, consisting of blood-perfused microvessels recapitulating the printed pattern. The results obtained in this study favor the development of new therapeutic approaches for critical clinical conditions, such as the need for prompt revascularization of ischemic tissues, which represents the fundamental substrate for advanced regenerative medicine applications.
KW - 3D bioprinting
KW - extracellular vesicles
KW - innovative bioinks
KW - neovascularization
KW - 3D bioprinting
KW - extracellular vesicles
KW - innovative bioinks
KW - neovascularization
UR - http://hdl.handle.net/10807/176859
U2 - 10.1088/1758-5090/abdacf
DO - 10.1088/1758-5090/abdacf
M3 - Article
SN - 1758-5082
VL - 2021
SP - N/A-N/A
JO - Biofabrication
JF - Biofabrication
ER -