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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Mimicking human skin constructs using

                                        norbornene-pullulan-based hydrogels



                                        Angela Cirulli 1 id , Livia Neves Borgheti-Cardoso 1 id , Núria Torras * ,
                                                                                              1 id
                                        and Elena Martínez 1,2,3 id
                                                           *
                                        1 Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia,
                                        The Barcelona Institute of Science and Technology, Barcelona, Spain
                                        2 Centro de Investigación Biomédica en Red, Madrid, Spain
                                        3 Department of Electronics and Biomedical Engineering, University of Barcelona, Barcelona, Spain




                                        Abstract
                                        There has been a huge demand for engineered skin tissues in the realms of both
                                        in vitro and  in vivo applications. Selecting the right material scaffold is a critical
                                        consideration in making engineered skin tissues, since it should possess a good
                                        balance between elasticity and mechanical stability while promoting an adequate
                                        cell microenvironment to support both the dermal and the epidermal compartments
                                        of skin tissue. In this study, 3D-bioprinted norbornene-pullulan photocrosslinkable
                                        hydrogels were utilized as alternative scaffolds to produce epithelized dermal skin
                                        models. By employing visible light, 2.5 mm  cell-laden hydrogels could be printed
                                                                            3
                                        in 10 s. The thiol-ene photocrosslinking chemistry employed in this work enabled
            *Corresponding authors:     the formation of a well-defined extracellular matrix with orthogonal crosslinks,
            Núria Torras
            (ntorras@ibecbarcelona.eu)  where encapsulated fibroblasts maintained high cellular viability rates.  Through
            Elena Martínez              this method, an epidermal layer could be grown on top of the fibroblasts.  The
            (emartinez@ibecbarcelona.eu)  coexistence and interaction of human fibroblasts and keratinocytes were visualized
                                        by determining the expression of specific markers.  This approach represents a
            Citation: Cirulli A,
            Borgheti-Cardoso LN, Torras N,    promising starting point for the development of photocrosslinkable hydrogel-based
            Martínez E. Mimicking human   human skin constructs by using thiol-ene norbornene chemistry, paving the way
            skin constructs using norbornene-  toward manufacture of complex in vitro models of human tissues.
            pullulan-based hydrogels.
            Int J Bioprint. 2024;10(4):3395.
            doi: 10.36922/ijb.3395
                                        Keywords: Skin models; Photocrosslinkable hydrogels; Pullulan;
            Received: April 9, 2024     Light-based 3D bioprinting
            Accepted: May 24, 2024
            Published Online: July 3, 2024
            Copyright: © 2024 Author(s).
            This is an Open Access article
            distributed under the terms of the   1. Introduction
            Creative Commons Attribution
            License, permitting distribution,   The skin structure can be organized into three major layers, namely hypodermis,
            and reproduction in any medium,   dermis, and epidermis, with each of the layers providing different mechanical properties
            provided the original work is   depending on its cellular composition and type of structure.  Engineered skin tissues
                                                                                         1
            properly cited.
                                        can  be  employed  in  clinical  applications,  including  skin  substitution and  advanced
            Publisher’s Note: AccScience   wound dressing, as well as in the pre-clinical scenarios to facilitate drug absorption,
            Publishing remains neutral with   disease modeling, and cosmetic studies. An ideal engineered skin tissue should be easy
            regard to jurisdictional claims in
            published maps and institutional   to prepare, resistant mechanical shear forces, and suitable for cells to adhere, grow, and
            affiliations.               vascularize, in both epidermal and dermal compartments. 2,3




            Volume 10 Issue 4 (2024)                       222                                doi: 10.36922/ijb.3395
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