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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

