Anagrafe della ricerca

3D-BIOSAME project will develop physiological in vitro platforms expected to improve our current capabilities to boost the biological machinery that triggers regeneration in the injured spinal cord (SC) of mammals, in a therapeutic perspective. Studies in vivo provide important step-forwards, as an important approach for translational research, although showing several limitations. The in vitro platforms represent an alternative strategy. Not only do they reduce ethical and cost concerns, they also have the potential for patient-specific customization. Thus, in vitro platforms offer the unique potential to combine the features of the experimental system-model with the biological properties of tissues and organs, achieving the final goal of recapitulating the complex human physiology in vitro. At present, a full exploitation of this technology in neural regeneration is far from being achieved, and methods to produce a physiologically-relevant SC model are missing. The complexity of the mammalian SC structure and its heterogeneous composition hamper research efforts towards the development of in vitro SC recapitulating the key features of the in vivo mammalian context. 3D-BIOSAME aims to realize for the first time a 3D bioprinted SC model combining sensory, cortical and motor neurons with the glia counterpart in an in vivo-like framework. Three-D bioprinting is a cell-friendly method to fabricate cellularized scaffolds with defined geometry and multiple cell phenotypes. The use of ad hoc designed bioinks steers the cell towards high viability maximizing cell-cell, cell-extracellular environment interactions resulting in a more closely-matching of the in vivo scenario. We will utilize murine cells to establish the design and processing protocols of the model, whose reliability will be tested by comparing its response to injury with that of murine models. At present, generation of in vivo models of spinal cord injury (SCI) is a highly invasive, time-consuming process requiring a large number of animals to obtain relevant data of statistical significance. Experiments in vitro can strongly reduce these drawbacks. In this regard, we will propose in vitro SCI models by applying 2 different types of damage to central axons (classical mechanical injury and innovative toxin-based approach) and then monitor the ensuing axonal degeneration and glial activation. Next, known pro-regenerative agents, as well as a novel compound recently identified by UNIPD, will be used to boost regeneration. Indeed, we believe that the 3D model holds the potential to become a screening platform for the validation of novel pro-regenerative molecules, in a therapeutic perspective. 3D-BIOSAME will benefit from the scientific interaction among researchers having a multidisciplinary background with key expertise in biomedical engineering (POLITO), in vitro and in vivo mice models (UNITO), mammalian nerve regeneration (UNIPD), and materials characterization (CNR).