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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Development of multi-layered 3D-printed

                                        scaffold for sequential delivery of biomolecules



                                        Jong-Eun Won 1 id , Hyun Kyung Moon 2 id , Hae-Won Kim * , and Ji Suk Shim *
                                                                                      3,4 id
                                                                                                         1,5 id
                                        1  Institute of Clinical Dental Research, Korea University Guro Hospital, Seoul, South Korea
                                        2  Department of Medicine, Korea University Graduate School, Seoul, South Korea
                                        3  Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, South Korea
                                        4  Department of Nano-Biomedical Science & BK21 NBM Global Research Center for Regenerative
                                        Medicine, Dankook University, Cheonan, South Korea
                                        5  Department of Dentistry, Korea University Guro Hospital, Seoul, South Korea



                                        Abstract

                                        Spatiotemporal control of exogenous growth factors plays a crucial role in the
                                        sequential repair of damaged tissues. However, traditional therapeutic trials
                                        have mostly relied on the delivery of a single molecule due to limitations in
                                        rapid  diffusion  and  the  instability  of  biomolecules.  In  this  study,  we  developed
                                        a novel strategy using a composite of gelatin and silica as an alternative for the
                                        stable and sequential release of biomolecules. Two biomolecules, basic fibroblast
                                        growth  factor, and  bone morphogenetic  protein-2,  were incorporated  into two
            *Corresponding authors:     separate composites and sequentially layered onto the activated polymer surface.
            Hae-Won Kim                 Each molecule was sequentially released from each layer of the scaffold, and the
            (kimhw@dku.edu)             silica composite prevented rapid diffusion due to its nanoporous structure.  The
            Ji Suk Shim                 adhesion, proliferation, and osteogenic differentiation of rat bone marrow-derived
            (shoss@korea.ac.kr)
                                        mesenchymal stem cells were significantly enhanced in the double-layered group
            Citation: Won JE, Moon HK,    containing separately delivered dual molecules compared with the control or single
            Kim HW, Shim JS. Development of   groups.  Our  developed  gelatin-silica  composite  was  successfully  incorporated  in
            multi-layered 3D-printed scaffold for
            sequential delivery of biomolecules.   double layers on polymer scaffolds, and cellular responses were promoted in this
            Int J Bioprint. 2024;10(6):4638.    manner.  These results demonstrated that our scaffolding system has potential
            doi: 10.36922/ijb.4638      as a therapeutic strategy for the delivery of dual or multiple biomolecules in
            Received: August 23, 2024   regenerative medicine.
            Revised: September 20, 2024
            Accepted: September 24, 2024
            Published Online: September 24,   Keywords: Dual delivery; Basic fibroblast growth factor; Bone morphogenic protein;
            2024
                                        3D printing; Xerogel; Growth factor
            Copyright: © 2024 Author(s).
            This is an Open Access article
            distributed under the terms of the
            Creative Commons Attribution
            License, permitting distribution,   1. Introduction
            and reproduction in any medium,
            provided the original work is   To repair damaged tissue, endogenous signal molecules, including cytokines, chemokines,
            properly cited.             and growth factors (GFs), are required in dynamic cellular processes.  Among
                                                                                                     1,2
            Publisher’s Note: AccScience   these, GFs, including fibroblast GFs (FGFs), platelet-derived GFs (PDGFs), vascular
            Publishing remains neutral with   endothelial GFs (VEGFs), and bone morphogenetic proteins (BMPs), spatiotemporally
            regard to jurisdictional claims in
            published maps and institutional   modulate various cellular responses, such as adhesion, proliferation, migration, and
            affiliations.               differentiation. Cellular signaling affects tissue repair and healing processes to overcome



            Volume 10 Issue 6 (2024)                       444                                doi: 10.36922/ijb.4638
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