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International Journal of Bioprinting


                                        RESEARCH ARTICLE
                                        Pore size-mediated macrophage M1 to M2

                                        transition affects osseointegration of 3D-printed
                                        PEEK scaffolds



                                        Xiaopeng Yang , Jianbo Gao , Shenyu Yang , Yan Wu , Huilong Liu ,
                                                                 2
                                                     1,2
                                                                              2
                                                                                                 2
                                                                                     2
                                        Danyang Su , Dichen Li *
                                                  2
                                                            1
                                        1 State Key Lab for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an 710049,
                                        China
                                        2 The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
                                        Abstract
                                        Increasing evidence indicates that macrophages play an important role in angiogenesis
                                        and  bone  regeneration.  Because  the  phenotypic  polarization  of  macrophage  is
                                        extremely sensitive to the pore size of materials, poly(ether-ether-ketone) (PEEK)
                                        scaffolds with pore sizes of 0, 200, and 400 μm were prepared, and the influence
                                        of pore size-mediated macrophage polarization on subsequent angiogenesis and
                                        osteogenesis was examined. The interaction results of macrophages and scaffolds
                                        indicated that macrophages were responsive to the pore size of three-dimensional
                                        (3D)-printed PEEK scaffolds, and large pore size scaffolds showed greater potential
                                        in inducing M1 to M2 transition of macrophage and enhanced macrophage
                                        secretion of high concentrations of osteogenesis-related and angiogenesis-related
                                        cytokines. When human umbilical vein endothelial cells (HUVECs) and bone marrow
                                        mesenchymal stem cells (BMSCs) were cultured in the conditioned medium derived
            *Corresponding author:
            Dichen Li (dcli@mail.xjtu.edu.cn)  from co-culture of macrophages and scaffolds, HUVECs showed good angiogenic
                                        responses in terms of cell migration and angiogenic gene expression, while BMSCs
            Citation: Yang X, Gao J, Yang S,
            et al., 2023, Pore size-mediated   showed good osteogenic differentiation effect in  in vitro mineralization and
            macrophage M1 to M2 transition   osteogenesis-related gene expression. The results of bone defect repair showed that
            affects osseointegration of   the bone volume/total volume ratio and trabecular thickness of the large pore size
            3D-printed PEEK scaffolds.
            Int J Bioprint, 9(5): 755.   PEEK scaffold were significantly higher, and it had better biomechanical properties
            https://doi.org/10.18063/ijb.755  and achieved a better osseointegration effect. Our data demonstrate that large-pore
                                        PEEK scaffolds promote angiogenesis and osteogenic differentiation  in vitro and
            Received: December 1, 2022
            Accepted: February 12, 2023  osseointegration in vivo, most likely because scaffolds with larger pore size are able
            Published Online: May 17, 2023  to mediate a higher degree of M1 to M2 transition in macrophages.
            Copyright: © 2023 Author(s).
            This is an Open Access article
            distributed under the terms of the   Keywords: PEEK; 3D printing; Pore size, Macrophage, Osseointegration
            Creative Commons Attribution
            License, permitting distribution,
            and reproduction in any medium,
            provided the original work is
            properly cited.             1. Introduction
            Publisher’s Note: Whioce    In the past decades, in order to improve the osseointegration ability of bone repair
            Publishing remains neutral with   materials with host bone, researchers have mainly focused on designing or modifying
            regard to jurisdictional claims in   bone repair materials to induce differentiation of bone marrow mesenchymal stem
            published maps and institutional
            affiliations.               cells (BMSCs) into osteoblasts [1,2] . However, when the bone repair material is implanted



            Volume 9 Issue 5 (2023)                        128                         https://doi.org/10.18063/ijb.755
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