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International Journal of Bioprinting                                Stretchable scaffold for modeling fibrosis




            in fibrosis, compared to scaffolds under static conditions.   Software:  Mattia Spedicati,  Francesca Tivano, Janira Bei,
            In particular, stimulated cells had increased expressions   Mario Lavella
            of the  α-SMA and fibronectin and decreased expression   Supervision: Irene Carmagnola, Valeria Chiono
            of collagen III.  These results supported the hypothesis   Validation: Mattia Spedicati, Francesca Tivano, Janira Bei,
                        48
            that the application of cyclic mechanical stimulations   Mario Lavella, Alice Zoso
            to  cellularized bioartificial  scaffolds may  trigger  HCF   Writing – original draft: Mattia Spedicati, Francesca Tivano
            activation into myofibroblasts. Deeper investigations   Writing – review & editing: Mario Lavella, Alice Zoso, Irene
            through protein and gene expression quantifications (e.g.,   Carmagnola, Valeria Chiono
            qPCR) are warranted to validate the effect of mechanical
            stimulation on HCF phenotype and culture time. This   Ethics approval and consent to participate
            system would allow us to better understand and manage   Not applicable.
            fibrosis onset by tuning stretch timing and rate.
               In summation, the mechanical and biological properties   Consent for publication
            of bioartificial PCL/GelMA scaffolds make them a   Not applicable.
            promising platform with in vivo-like mechanical properties,
            tailored by PCL scaffold architecture and GelMA hydrogel   Availability of data
            concentration, for the development of dynamic  in vitro
            models of human cardiac fibrotic tissues. Further validation   Data  are  available  from  the  corresponding  author  upon
            will allow their use for the  in vitro preclinical testing of   reasonable request.
            medical devices and advanced therapies.
                                                               References
            Acknowledgments
                                                               1.   World Health Organization (WHO).  Cardiovascular
            The authors would like to acknowledge CellScale (Canada)   Diseases (CVDs).
            for kindly lending us the MechanoCulture T6 bioreactor      https://www.Who.Int/En/News-Room/Fact-Sheets/Detail/
            and especially Johannes de Bondt (Business Unit Manager,   Cardiovascular-Diseases-(Cvds); 2019.
            Germany at World Precision Instruments - Europe) for   2.   Talman V,  Ruskoaho H.  Cardiac fibrosis  in myocardial
            his support.                                          infarction—from repair and remodeling to regeneration.
                                                                  Cell Tissue Res. 2016;365(3):563-581.
            Funding                                               doi: 10.1007/s00441-016-2431-9
            This work was supported by the European Research   3.   Woodruff MA, Hutmacher DW. The return of a forgotten
            Council (ERC) under the European Union’s Horizon 2020   polymer – polycaprolactone in the 21st century. Prog Polym
            research and innovation funding program (BIORECAR;    Sci. 2010;35(10):1217-1256.
            Grant Agreement No. 772168).                          doi: 10.1021/acsami.3c04362
                                                               4.   Nichol  JW, Koshy  ST,  Bae H,  Hwang  CM, Yamanlar  S,
            Conflict of interest                                  Khademhosseini A. Cell-laden microengineered gelatin
                                                                  methacrylate hydrogels. Biomaterials. 2010;31(21):5536-5544.
            The authors declare no conflicts of interest.         doi: 10.1016/j.biomaterials.2010.03.064

            Author contributions                               5.   Deddens JC, Sadeghi AH, Hjortnaes J, et al. Modeling the
                                                                  human scarred heart in vitro: toward new tissue engineered
            Conceptualization: Irene Carmagnola, Valeria Chiono   models. Adv Healthc Mater. 2017;6(3):1-21.
            Data curation: Mattia Spedicati, Francesca Tivano, Janira      doi: 10.1002/adhm.201600571
               Bei, Mario Lavella, Alice Zoso                  6.   Olvera D, Sohrabi Molina M, Hendy G, Monaghan MG.
            Formal analysis: Mattia Spedicati, Francesca Tivano, Janira   Electroconductive melt electrowritten patches matching the
               Bei, Mario Lavella                                 mechanical anisotropy of human myocardium. Adv Funct
            Funding acquisition: Valeria Chiono                   Mater. 2020;30(44):1-10.
            Investigation:  Mattia Spedicati, Francesca Tivano, Janira      doi: 10.1002/adfm.201909880
               Bei, Mario Lavella, Alice Zoso                  7.   Castilho M, van Mil A, Maher M, et al. Melt electrowriting
            Methodology:  Mattia Spedicati, Francesca Tivano, Janira   allows tailored microstructural and mechanical design of
               Bei, Mario Lavella, Alice Zoso                     scaffolds to advance functional human myocardial tissue
            Project administration: Valeria Chiono                formation. Adv Funct Mater. 2018;28(40):1-10.
            Resources: Valeria Chiono                             doi: 10.1002/adfm.201803151.



            Volume 10 Issue 3 (2024)                       486                                doi: 10.36922/ijb.2247
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