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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Spatiotemporal delivery of BMP-2 and FGF-18 in

                                        3D-bioprinted tri-phasic osteochondral scaffolds
                                        enhanced compartmentalized osteogenic and

                                        chondrogenic differentiation of mesenchymal
                                        stem cells isolated from rats with varied

                                        organizational morphologies



                                        Weiwei Su 1,2† id , Shiyu Li 1,3† id , Panjing Yin 1,3† id , Weihan Zheng 1,3 id , Ling Wang 4 id ,
                                        Zhuosheng Lin 1 id , Ziyue Li 1,3 id , Zi Yan 1,3 id , Yaobin Wu * , Chong Wang * ,
                                                                                     1 id
                                                                                                    5 id
                                        and Wenhua Huang 1,2,3 id
                                                           *
                                        1 Guangdong  Engineering  Research  Center  for  Translation  of  Medical  3D  Printing  Application,
                                        Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key
                                        Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University,
                                        Guangzhou, Guangdong, China
            † These authors contributed equally   2 Department  of  Orthopedics,  Affiliated  Hospital  of  Putian  University,  Putian  University,  Putian,
            to this work.               Fujian, China
                                        3 The  Third  Affiliated  Hospital  of  Southern  Medical  University,  Guangdong  Medical  Innovation
            *Corresponding authors:
            Yaobin Wu                   Platform for Translation of 3D Printing Application, Southern Medical University, Guangzhou,
            (wuyaobin2018@smu.edu.cn)   Guangdong, China
                                        4 Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University,
            Chong Wang
            (wangchong@dgut.edu.cn)     Guangzhou, Guangdong, China
            Wenhua Huang                5 Department  of  Intelligent  Manufacturing  Engineering,  School  of  Mechanical  Engineering,
            (hwh@smu.edu.cn)            Dongguan University of Technology, Songshan Lake, Dongguan, Guangdong, China
            Citation: Su W, Li S, Yin P, et al.
            Spatiotemporal delivery of
            BMP-2 and FGF-18 in 3D-bioprinted
            tri-phasic osteochondral scaffolds   Abstract
            enhanced compartmentalized
            osteogenic and chondrogenic
            differentiation of mesenchymal stem   Replicating the heterogeneous structure and promoting compartmentalized
            cells isolated from rats with varied   osteogenesis/chondrogenesis are critical considerations in designing scaffolds for
            organizational morphologies.    osteochondral tissue regeneration. However, desirable osteochondral regeneration
            Int J Bioprint. 2024;10(5):3229.
            doi: 10.36922/ijb.3229      cannot be achieved mainly due to the absence of effective delivery strategies for
                                        growth factors (GFs) and the insufficiency of desirable organizational morphologies
            Received: March 21, 2024    for seed cells. Herein, we developed a tri-phasic osteochondral scaffold consisting of
            Accepted: May 13, 2024
            Published Online: July 2, 2024  bone morphogenetic protein-2 (BMP-2)-loaded subchondral layer, fibroblast growth
                                        factor-18 (FGF-18)-loaded cartilage layer, and an interface layer that acted as a barrier
            Copyright: © 2024 Author(s).
            This is an Open Access article   to reduce the mutual interference of GFs, via cryogenic 3D bioprinting. BMP-2 could
            distributed under the terms of the   exert osteogenic effects for 14 days, and FGF-18 could exert chondrogenic effects for
            Creative Commons Attribution   21 days, demonstrating the time-controlled release function of BMP-2 and FGF-18.
            License, permitting distribution,
            and reproduction in any medium,   By further seeding discrete rat bone marrow mesenchymal stem cells (rBMSCs) and
            provided the original work is   rBMSC microspheres, respectively, onto the subchondral layer and cartilage layer,
            properly cited.             the engineered cell-laden osteochondral tissue was constructed. The spatiotemporal
            Publisher’s Note: AccScience   release of BMP-2 and FGF-18 in the subchondral layer and cartilage layer promoted
            Publishing remains neutral with   the osteogenic differentiation of discrete rBMSCs and chondrogenic differentiation
            regard to jurisdictional claims in
            published maps and institutional   of rBMSC microspheres in the subchondral layer and cartilage layer, respectively.
            affiliations.               In summary, by seeding rBMSCs with varied organizational morphologies in



            Volume 10 Issue 5 (2024)                       198                                doi: 10.36922/ijb.3229
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