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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Induction and real-time ultrasonic monitoring

                                        of 3D cartilage-like tissue by a low shear
                                        stresses-based bioreactor



                                        Daniel Martínez-Moreno 1,2,3,4,5 id , Antonio Callejas 1,4,6 id , Gema Jiménez 1,2,3,4,5 id ,
                                                                           * , and Juan Antonio Marchal
                                                                                                          *
                                        Patricia Gálvez-Martín , Guillermo Rus 1,4,6 id              1,2,3,4,5 id
                                                           7
                                        1 Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, Granada, Spain
                                        2 Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research,
                                        University of Granada, Granada, Spain
                                        3 Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada,
                                        Granada, Spain
                                        4 Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain
                                        5 Biofabrication and 3D (bio)printing (BioFab i3D) laboratory, University of Granada, Granada, Spain
                                        6 Department of Structural Mechanics and Hydraulic Engineering, Faculty of Civil, Canal and Port
                                        Engineering, Granada, Spain
                                        7
                                        R&D Human and Animal Health Team, Bioiberica S.A.U., Barcelona, Spain


            *Corresponding authors:     Abstract
            Guillermo Rus
            (grus@go.ugr.es)            Osteoarthritis is a significant socioeconomic illness that mainly affects the articular
            Juan Antonio Marchal        cartilage, a tissue with a low capacity for self-healing, making it an ideal target
            (jmarchal@go.ugr.es)
                                        for regenerative medicine and tissue engineering. Current interventions to treat
            Citation: Martínez-Moreno D,   cartilage injuries may not be completely effective. In this study, we have developed
            Callejas A, Jiménez G,
            Gálvez-Martín P, Rus G,     a novel bioreactor that creates viscous shear stress by flow perfusion. This bioreactor
            Marchal JA. Induction and    could induce ex vivo maturation of biomimetic 3D cartilage scaffolds, providing a

            real-time ultrasonic monitoring of    potential solution to this problem. Infrapatellar fat pad mesenchymal stem cells
            3D cartilage-like tissue by a low
            shear stresses-based bioreactor.    (IPFP-MSCs) were used as a cellular source of the functionalized 3D scaffolds made
            Int J Bioprint. 2024;10(4):3389.     of 1,4-butanediol thermoplastic polyurethane (bTPUe) modified with pyrene
            doi: 10.36922/ijb.3389      butyric acid (PBA). Our results indicate that our bioreactor induced chondrogenic
            Received: April 9, 2024     differentiation, as confirmed by DNA quantification, extracellular matrix
            Accepted: May 9, 2024       determination, and metabolic assay, without any conditioned medium. To control
            Published Online: July 12, 2024  the biomechanical stimulation on IPFP-MSCs, a low-intensity ultrasonic transmission
            Copyright: © 2024 Author(s).   system has been developed and embedded in the bioreactor. Combined with a finite
            This is an Open Access article   element model (FEM), tissue growth and differentiation can be deconvoluted in real-
            distributed under the terms of the
            Creative Commons Attribution   time from the recorded ultrasonic propagation and interaction across the graft. The
            License, permitting distribution,   FEM reconstructs this complex interaction. This is the first time a low-shear stress-
            and reproduction in any medium,   based bioreactor has been reported to not only induce chondrogenic evolution but
            provided the original work is
            properly cited.             also monitor it in real time.
            Publisher’s Note: AccScience
            Publishing remains neutral with   Keywords: Scaffolds; Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs);
            regard to jurisdictional claims in
            published maps and institutional   1,4-Butanediol thermoplastic polyurethane (bTPUe); Cartilage; Bioreactor;
            affiliations.               Ultrasounds






            Volume 10 Issue 4 (2024)                       366                                doi: 10.36922/ijb.3389
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