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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Near-infrared controlled release of mesenchymal

                                        stem cells secretome from bioprinted graphene-
                                        based microbeads for nerve regeneration



                                        Giordano Perini , Valentina Palmieri , Marcello D’Ascenzo , Claudia Colussi ,
                                                     1,2
                                                                                           1,2
                                                                                                           2,4
                                                                        2,3
                                        Claudio Grassi , Ginevra Friggeri , Alberto Augello , Lishan Cui ,
                                                                     2
                                                    1,2
                                                                                              1
                                                                                    2
                                        Massimiliano Papi *, and Marco De Spirito 1,2
                                                        1,2
                                        1 Dipartimento  di Neuroscienze,  Università Cattolica del Sacro Cuore, Largo Francesco Vito 1,
                                        00168 Rome, Italy
                                        2 Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
                                        3 Istituto dei Sistemi Complessi, CNR, Via dei Taurini 19, 00185 Rome, Italy
                                        4 Istituto di analisi  dei  sistemi  ed informatica  “Antonio  Ruberti,”  CNR,  Via  dei  Taurini  19, 00185
                                        Rome, Italy
                                        (This article belongs to the Special Issue: Advances in 3D bioprinting for regenerative medicine and drug
                                        screening)
                                        Abstract
                                        Nerve damage is a prevalent and debilitating condition with limited treatment options.
                                        Recent years have seen an increased incidence of neural damage due to factors such
                                        as aging populations and traumatic brain injuries. Addressing the urgent need for
                                        effective therapies, this study explores the controlled delivery of mesenchymal stem
                                        cells (MSCs) secretome, a complex mixture of bioactive factors, which is currently being
            *Corresponding author:      investigated for its potential in nerve regeneration. The secretome offers significant
              Massimiliano Papi         advantages over stem cells themselves, as it can be more easily characterized and
            (massimiliano.papi@unicatt.it)  controlled, enabling precise regulation of therapeutic interventions. However, the
            Citation: Perini G, Palmieri   challenge lies in delivering the secretome specifically to the target anatomical region.
            V, D’Ascenzo M, et al. Near-  To overcome this limitation, we propose a novel approach utilizing near-infrared
            infrared controlled release of
            mesenchymal stem cells secretome   (NIR) radiation-responsive bioprinted alginate-graphene oxide (AGO) microbeads.
            from bioprinted graphene-based   Graphene oxide (GO) is a highly biocompatible material with unique properties,
            microbeads for nerve regeneration.   including NIR responsiveness, enabling controlled release of therapeutic agents
            Int J Bioprint. 2024;10(1):1045.
            doi: 10.36922/ijb.1045      upon NIR exposure. We hypothesized that AGO microbeads could encapsulate MSCs
                                        secretome and release it in a controlled manner using NIR radiation. To investigate
            Received: June 5, 2023
            Accepted: July 10, 2023     our hypothesis, controlled damage was induced to hippocampal neurons, and
            Published Online: August 4, 2023  MSCs secretome was encapsulated within AGO microbeads. Subsequently, NIR
                                        radiation was applied to trigger the release of the secretome.  We compared the
            Copyright: © 2023 Author(s).
            This is an Open Access article   efficacy of MSCs secretome with that of astrocytes, which also possess nerve growth
            distributed under the terms of the   and proliferation-promoting capabilities.  Our findings demonstrated that the
            Creative Commons Attribution   controlled release of MSCs secretome from AGO microbeads through non-invasive
            License, permitting distribution,
            and reproduction in any medium,   NIR radiation significantly promoted the proliferation and regeneration of neurons
            provided the original work is   following nerve injury. AGO microbeads offer multiple advantages over conventional
            properly cited.             delivery methods, including precise control over the timing, location, and dosage
            Publisher’s Note: AccScience   of therapeutic agents. Furthermore, the potential for reduced immunogenicity and
            Publishing remains neutral with   tumorigenicity enhances the safety profile of the therapy. Consequently, this study
            regard to jurisdictional claims in
            published maps and institutional   presents a promising avenue for the development of MSC-based therapies for nerve
            affiliations.               regeneration, with implications for the treatment of various neuropathies and injuries.



            Volume 10 Issue 1 (2024)                       229                          https://doi.org/10.36922/ijb.1045
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