3D-printed IFN-γ-loading calcium silicate-β-tricalcium phosphate scaffold sequentially activates M1 and M2 polarization of macrophages to promote vascularization of tissue engineering bone
3D-printed IFN-γ-loading calcium silicate-β-tricalcium phosphate scaffold sequentially activates M1 and M2 polarization of macrophages to promote vascularization of tissue engineering bone
复制标题
3D打印的负载IFN-γ的硅酸钙-β-磷酸三钙支架依次激活巨噬细胞的M1和M2极化，促进组织工程骨的血管化
DOI：
10.1016/j.actbio.2018.03.012
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发表时间：
2018-04-15
影响因子：
9.7
通讯作者：
Wang, Jinwu
中科院分区：
文献类型：
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作者：
Li, Tao;Peng, Mingzheng;Wang, Jinwu
为了促进组织工程骨的血管化，将ifn - γ极化到M1的巨噬细胞装载在5%硅酸钙/ β -磷酸三钙（casio3 - β - tcp）支架上。从支架中释放的ifn - γ和Si分别使M1和M2巨噬细胞极化。制备β - tcp、casio3 - β - tcp和IFN-gamma@CaSiO3-beta-TCP，并进行生物相容性评价。流式细胞术检测巨噬细胞极化。用载于支架上巨噬细胞培养物提取的条件培养基在Matrigel上培养和诱导含GFP的人脐静脉内皮细胞，以评价血管生成。将支架皮下植入C57B1/6 4周后，通过肉眼观察、苏木精染色、伊红染色及CD31免疫组化评价支架血管的形成情况。结果表明IFN-gamma@CaSiO3-beta-TCP支架在早期（1-3天）释放ifn - γ刺激巨噬细胞向M1极化，随后释放Si诱导巨噬细胞向M2极化，同时支架降解。M1/M2的激活使巨噬细胞分泌更多的细胞因子，包括VEGF、CXCL12和PDGF-BB。与对照组相比，IFN-gamma@CaSiO3-beta-TCP支架在体外和体内形成了更多的血管。本研究表明，设计具有免疫调节功能的组织工程支架，利用宿主巨噬细胞增加组织工程骨的血管化，为加速组织工程支架的血管化和成骨提供了新的策略，显示了治疗重大骨缺损的潜力。(C) 2018材料学报Elsevier Ltd.出版。版权所有。
To promote vascularization of tissue-engineered bone, IFN-gamma polarizing macrophages to M1 was loaded on 5% calcium silicate/beta-tricalcium phosphate (CaSiO3-beta-TCP) scaffolds. IFN-gamma and Si released from the scaffold were designed to polarize M1 and M2 macrophages, respectively. beta-Tcp, CaSiO3-beta-TCP, and IFN-gamma@CaSiO3-beta-TCP were fabricated and biocompatibilities were evaluated. Polarizations of macrophages were detected by flow cytometry. Human umbilical vein endothelial cells with GFP were cultured and induced on Matrigel with conditioned culture medium extracted from culture of macrophages loaded on scaffolds for evaluating angiogenesis. Four weeks after the scaffolds were subcutaneously implanted into C57B1/6, vascularization was evaluated by visual observation, hematoxylin and eosin staining, as well as immunohistochemistry of CD31. The results showed that IFN-gamma@CaSiO3-beta-TCP scaffolds released IFN-gamma in the early stage (1-3 days) to stimulate macrophages to M1 polarization, followed by release of Si inducing macrophages to M2 polarization while scaffolds degraded. The activation of M1/M2 allows macrophages to secrete more cytokines, including VEGF, CXCL12 and PDGF-BB. The IFN-gamma@CaSiO3-beta-TCP scaffolds formed more blood vessels in vitro and in vivo compared to the control groups. The study indicated that the design of tissue-engineered scaffolds with immunomodulatory function utilized host macrophages to increase vascularization of tissue-engineered bone, providing a new strategy for accelerating vascularization and osteogenesis of tissue-engineered scaffolds and showing the potential for treatment of major bone defects. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.